Biol Reprod
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

BOR - Papers in Press, published online ahead of print March 2, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.036277
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
73/1/54    most recent
biolreprod.104.036277v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burns, D. S.
Right arrow Articles by Ireland, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burns, D. S.
Right arrow Articles by Ireland, J. J.
Agricola
Right arrow Articles by Burns, D. S.
Right arrow Articles by Ireland, J. J.
BIOLOGY OF REPRODUCTION 73, 54–62 (2005)
DOI: 10.1095/biolreprod.104.036277
© 2005 by the Society for the Study of Reproduction, Inc.

Numbers of Antral Follicles During Follicular Waves in Cattle: Evidence for High Variation Among Animals, Very High Repeatability in Individuals, and an Inverse Association with Serum Follicle-Stimulating Hormone Concentrations1

David S. Burns 3, Fermin Jimenez-Krassel 3, Janet L.H. Ireland 3, Phil G. Knight 4, and James J. Ireland 2 3

Molecular Reproductive Endocrinology Laboratory, Department of Animal Science,3 Michigan State University, East Lansing, Michigan 48824 School of Animal and Microbial Sciences,4 University of Reading, Reading RG6 2AJ, United Kingdom


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The extent, causes, and physiological significance of the variation in number of follicles growing during ovarian follicular waves in human beings and cattle are unknown. Therefore, the present study examined the variability and repeatability in numbers of follicles 3 mm or greater in diameter during the follicular waves in bovine estrous cycles, and we determined if the variation in number of follicles during waves was associated with alterations in secretion of FSH, estradiol, inhibin, and insulin-like growth factor I (IGF-I). Dairy cattle were subjected to twice-daily ultrasound analysis to count total number of antral follicles 3 mm or greater in diameter throughout 138 different follicular waves. In another study, blood samples were taken at frequent intervals from cows that consistently had low or very high numbers of follicles during waves and were subjected to immunoassays. Results indicate the following: First, despite an approximately sevenfold variation in number of follicles during waves among animals and marked differences in age, stage of lactation, and season of the year, a very highly repeatable (0.95) number of follicles 3 mm or greater in diameter is maintained during the ovulatory and nonovulatory follicular waves of individuals. Second, variation in number of follicles 3 mm or greater in diameter during waves and the inverse association of number of follicles during waves with FSH are not directly explained by alterations in the patterns of secretion of estradiol, inhibin, or IGF-I. Third, ovarian ultrasound analysis can be used reliably by investigators to identify cattle that consistently have low or high numbers of follicles during waves, thus providing a novel experimental model to determine the causes and physiological significance of the high variation in antral follicle number during follicular waves among single-ovulating species, such as cattle or humans.

estradiol, follicle, follicle-stimulating hormone, follicular development, inhibin


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Numbers of primordial follicles are highly variable at birth in cattle [1]. Because the ovarian reserve, which is comprised predominantly of primordial follicles, is depleted during aging and never replenished [1], numbers of the different follicle types in the ovarian reserve vary greatly among individual adult cattle [1]. However, despite high variability and chronic age-related depletion of the ovarian reserve, cattle continue to ovulate one or, occasionally, two oocytes during each estrous cycle throughout most of their relatively long reproductive life spans. Nevertheless, it is unknown if the high variation in number of follicles in ovarian reserves among individuals causes a highly variable number of nonovulatory follicles to grow during estrous cycles. This question is especially important to resolve, because in cattle, relatively high numbers of antral follicles are positively associated with an increased responsiveness to gonadotropin treatments during superovulation [2–5], a larger number of oocytes recovered for in vitro fertilization [4], a higher percentage of normal oocytes [3, 4], a greater number of transferable embryos [4], higher pregnancy rates following in vitro fertilization [4], shorter calving intervals [6], and fecundity [1, 6, 7]. Taken together, these observations imply that variation in number of follicles that develop during estrous cycles may have an important, albeit poorly understood, role in regulation of fertility in single-ovulating species, such as cattle.

Numerous investigators have used ultrasonography to firmly establish that two to three FSH-induced "waves" of antral follicle growth occur at 7- to 10-day intervals during bovine estrous cycles [8–12]. During each wave, the increase in FSH stimulates growth of a cohort of 3- to 4-mm antral follicles, which is followed by development of a single dominant, ovulatory-sized (12–20 mm) follicle and atresia of the remaining follicles in the original cohort [11, 13]. The wave-like pattern of growth and atresia of antral follicles that culminates in development of dominant ovulatory follicles in cattle [12], coincident with a shrinking ovarian reserve during aging [1], represents an important, albeit poorly understood, biological rhythm that must be maintained for successful reproduction. Nevertheless, despite the aforementioned positive association between numbers of follicles and numerous measures of fertility, the degrees of variation both between and among cattle in the number of follicles that grow during follicular waves are unknown, as are the causes, possible association with the ovarian reserve, and physiological significance of such variation.

The well-characterized bovine dominant follicle model was used in the present study to examine variation in the number of follicles 3 mm or greater in diameter during follicular waves and to determine if variation in follicle number is associated with alterations in key hormones or growth factors known to regulate folliculogenesis. Specifically, number of follicles in different follicular waves is hypothesized to be as variable within as it is among individual cattle because of the following: First, the size of the ovarian reserve, which may influence the number of follicles growing during waves, is highly variable among cattle and decreases as cattle age [1], and second, the different follicular waves during an estrous cycle occur in markedly different hormonal milieus [9]. To test this hypothesis, the first objective of the present study was to examine the variation in number of follicles during different nonovulatory and ovulatory follicular waves both among and within individual cattle of different ages and physiological stages of development. Furthermore, in cattle, FSH is the primary hormone that induces antral follicle growth during follicular waves [14], and antral follicles that grow during waves produce the chief FSH-negative feedback hormones, estradiol, and inhibin (INHA, or inhibin A, comprised of {alpha} and ßA subunits) [15, 16]. Insulin-like growth factor I (IGF-I) also interacts with FSH to promote follicle growth in laboratory species [17, 18] and to mimic or enhance FSH action on bovine granulosa cells [19]. Thus, the second objective of the present study was to test the hypothesis that the variation in number of follicles during follicular waves is positively associated with secretion of FSH, estradiol, INHA, and IGF-I.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Animals

Holstein heifers and lactating as well as nonlactating cows were obtained from the Michigan State University Dairy Cattle Teaching and Research Center. Heifers were housed in free stalls, whereas cows were housed in tie-stall barns. Animals were provided feed and water ad libitum. All rations met National Research Council requirements, and studies were conducted during the spring, summer, or fall of 2001 and 2002 and during the fall of 2003. The All University Committee on Animal Use and Care at Michigan State University sanctioned all procedures involving cattle.

Ultrasound Scanning Procedure to Count Antral Follicles 3 mm or Greater in Diameter in Ovaries

Ovaries in each cow were scanned with an Aloka SSD-900 linear array trans-rectal probe (7.5-MHz transducer; Aloka Ultrasound, Wallingford, CT). To standardize counting of follicles, each ovary was scanned from end to end to identify the positions of the corpus luteum and antral follicles. Video images for different ovarian sections were captured on a computer monitor, and the locations of the corpus luteum and each antral follicle 3 mm or greater in diameter in each section were drawn on an ovarian map. Two separate measurements of diameter were averaged for each follicle and recorded next to the appropriate follicle on each ovarian map. The scanning procedure was repeated to confirm the locations of follicles on each ovarian map. Total number of antral follicles 3 mm or greater in diameter per pair of ovaries for each animal was determined by counting the number of follicles 3 mm or greater in diameter on each map for each animal. It should be noted that total number of follicles counted during follicular waves reflects not only follicles growing in response to the transient increase in FSH that precedes each follicular wave [12] but also may include growing, nongrowing, and/or atretic follicles that may or may not be part of the FSH-induced follicular wave.

Validation of Ultrasound Scanning to Count Total Number of Antral Follicles 3 mm or Greater in Diameter in Ovaries

To examine the variability of counting follicles, repeatability of a single-ultrasound-operator counting of the total number of antral follicles 3 mm or greater in diameter in ovaries for five nonlactating, 3- to 5-yr-old cows on three separate occasions (10 min apart) twice daily (0800 and 1800 h) for 11 consecutive days beginning at random stages of the estrous cycle was calculated. In this study, number of follicles (range, 4–22 follicles/cow) counted by a single ultrasound operator at each different ultrasound session in individual cattle was highly repeatable (0.97, n = 330 counts). In addition, the correlation of the number of follicles counted in ovaries between two different operators during ultrasound analysis on each of 11 randomly chosen days during estrous cycles of five nonlactating cows was determined. The daily ultrasound session for each cow by each operator was approximately 1 h apart, and the results of counting follicles by each operator were not disclosed until the study ended. In this study, the daily follicle counts (range, 6–25 follicles/cow) between the two ultrasound operators were highly correlated (correlation, 0.92; P < 0.01; n = 55 counts/operator).

Study 1: Variability and Repeatability of Maximal Numbers of Follicles 3 mm or Greater in Diameter During Follicular Waves

Part A To examine the repeatability of number of follicles during different follicular waves in the same or consecutive estrous cycles, fourteen 10- to 12-mo-old heifers and sixteen 4- to 7-yr-old cows (nine cows at late stages of lactation, seven cows not lactating) were subjected to ultrasound analysis. All animals were treated with two i.m. injections of 25 mg of prostaglandin F2{alpha} (PGF2{alpha}; Lutalyse; Pharmacia-Upjohn Co., Kalamazoo, MI) spaced 11 days apart to induce luteolysis and synchronize occurrence of estrus. Each animal was subjected to twice-daily (0800 and 1800 h) ultrasound analysis by the same ultrasound operator (D.S.B.) for an entire estrous cycle beginning at the time of the second PGF2{alpha} injection and continuing until 2 days after spontaneous ovulation during the subsequent estrous cycle. At each ultrasound session, total number of antral follicles 3 mm or greater in diameter in the ovaries of each animal was determined.

Part B This study determined the repeatability of number of follicles during follicular waves of individual cattle using a different ultrasound operator (F.J.-K.). In this study, three heifers (age, 13 mo) and two lactating Holstein cows (age, 3–5 yr) were treated with PGF2{alpha} and subjected to twice-daily ultrasound analysis to count the number of follicles as explained in part A.

Part C In the first experiment, repeatability of the number of follicles during follicular waves in estrous cycles spaced 3 mo apart for the same four nonlactating cows (age, 4–7 yr) was examined. Estrous cycles were either spontaneous or synchronized with two or three injections of PGF2{alpha} spaced 11 days apart. Numbers of follicles were counted twice daily either throughout all the different follicular waves during each estrous cycle for two cows or only during the first wave of three consecutive estrous cycles for the remaining two cows.

In the second experiment, repeatability of follicle number during follicular waves in estrous cycles spaced approximately 15 mo apart for the same individuals was examined. To complete this study, seven of the original 10- to 12-mo-old heifers from part A were treated at 27 to 28 mo of age with two injections of PGF2{alpha} spaced 11 days apart. Each cow was subjected to twice-daily ultrasound analysis to determine repeatability of the maximal number of follicles during each of three to five waves in consecutive estrous cycles as explained above. At the beginning of the treatment period, the cows were approximately 2 mo postcalving and near peak lactation. The results from the ultrasound analysis of these cows were then compared with the previous results generated from ultrasound analysis of three to four waves for the same individuals as heifers.

In addition to repeatability, differences in the overall average for the maximal numbers of follicles during waves in estrous cycles compared with estrous cycles for the same animals 3 or 15 mo later were determined.

Study 2: Relationship of Variation in Maximal Number of Follicles 3 mm or Greater in Diameter During Follicular Waves with Development Dynamics of Dominant and Subordinate Follicles

The animals used in study 1 (parts A and B) were arbitrarily segregated into the following four groups based on the overall average for the maximal number of follicles during waves: low (≤15 follicles during waves; n = 30 waves, 9 animals), intermediate (16–20 follicles; n = 29 waves, 10 animals), high (21–25 follicles; n = 25 waves, 8 animals), and very high (>25 follicles; n = 30 waves, 8 animals). The number of follicles (average ± SEM) during waves for cattle segregated into the low, intermediate, high, or very high groups was 12.8 ± 1.5, 16.8 ± 1.7, 22.1 ± 1.9, and 33.8 ± 1.5, respectively. To determine if numbers of follicles during waves were associated with alterations in the growth dynamics of dominant and subordinate follicles, differences in day of emergence for each follicular wave, day of deviation, length of dominance, interval between ovulations, and maximal diameter of the dominant or subordinate follicle at deviation or during dominance for cattle with low, intermediate, high, and very high numbers of follicles during waves were examined. Definitions used to characterize follicular waves and dominant follicle growth are as follows: day of emergence, determined retrospectively (after growth of the dominant follicle) as the first day of the new wave that a follicle 4 mm or greater in diameter is detected by ultrasound minus 1 day; day of deviation, first day of a new wave that the largest or dominant follicle is consistently 1 mm or greater in diameter than the next largest or subordinate follicle throughout the wave minus 1 day; and length of dominance, interval from first day of deviation in a new wave until emergence of the next wave.

Study 3: Association of Patterns of FSH, Estradiol, INHA, and IGF-I Secretion with Number of Follicles 3 mm or Greater in Diameter During Follicular Waves

Animal selection A group of 3- to 5-yr-old cows (n = 25) at similar stages of late lactation were subjected to ultrasound analysis for two to three consecutive days, chosen at random during an estrous cycle, to identify cows with a low (≤15) or a very high (>25) number of follicles. Three animals in the low group and four in the very high group were identified for blood sampling. To determine number of follicles during waves, estrous cycles for these animals were synchronized with three consecutive injections of PGF2{alpha} spaced 11 days apart. Each animal was subjected to daily (0800 h) ultrasound analysis after each of the first two PGF2{alpha} injections and twice-daily (0800 and 1800 h) ultrasound analysis after the third PGF2{alpha} injection. Ultrasound analysis began at the time of each injection of PGF2{alpha} and ended 4 days after ovulation. Number of follicles during the first follicular wave after each PGF2{alpha} injection was determined as explained above. The day of ovulation after each PGF2{alpha} injection was defined as the first day that the ultrasound operator was unable to detect the dominant ovulatory follicle during scanning.

Blood collection. Blood samples (5 ml) were removed from each animal's tail vein beginning 48 h after the third PGF2{alpha} injection and continuing every 4 h until 24 h after ovulation. Thereafter, blood was collected every 8 h until 96 h after ovulation. Based on previous results [9], this blood-sampling regimen should span the days of an estrous cycle that coincide with the latest stages of development of a dominant ovulatory follicle and the initial stages of development of the first-wave dominant nonovulatory follicle.

Immunoassays

Concentrations of FSH, estradiol, and INHA were determined for all serum samples, whereas IGF-I concentrations in serum were determined at 8- to 24-h intervals.

Concentrations of FSH in duplicate 100-µl serum samples for each cow were determined using a previously validated, heterologous RIA [20]. Results of the FSH RIA correlate with those of in vitro bioassay of FSH bioactivity [21]. Ovine FSH (U.S. Department of Agriculture [USDA] oFSH-19-SIAFP-I-2) was used as radio-iodinated tracer, bovine FSH (USDA bFSH-I-2) as standard, and National Institute of Diabetes and Digestive and Kidney Diseases anti-oFSH-1 (AFP-C5288113; Rockville, MD) as antiserum. All samples were analyzed in a single FSH assay. The intra-assay coefficient of variation (CV) was 10.5%, and the sensitivity of the assay was 0.03 ng/ml.

Estradiol concentrations were determined in duplicate 500-µl serum samples previously extracted with ether using a modified version [22] of the commercial MAIA Kit (Polymedco, Inc., Courtlandt Manor, NY). Standard curves ranged from 0.20 to 50 pg/ml (0.04–10 pg/tube), and the median effective dose (mean ± SEM) for standard curves (n = 4) averaged 4.8 ± 0.8 pg/ml. Sensitivity of the assay was 0.04 ± 0.01 pg/ml. Inter- and intra-assay (n = 4 assays) CVs were 17.5% and 9.6%, respectively, for serum samples that averaged 5.1 pg/ml and 16.5% and 24.4%, respectively, for samples (n = 4) that averaged 0.88 pg/ml.

Concentration of IGF-I in serum samples was determined with use of a commercial two-site immunoradiometric assay (Diagnostic Systems Laboratories, Inc., Webster, TX) previously validated for bovine serum [23]. Serum samples (50 µl) were acid-ethanol extracted per the manufacturer's instructions and run in duplicate in a single assay. Assay of different volumes of cow serum (10–50 µl) was parallel with the standard curve (data not shown). The intra-assay CV for controls containing low (45.7 ± 1.8 ng/ml) or high (161.4 ± 13.6 ng/ml) concentrations of IGF-I was 7.8% and 16.8%, respectively, and the sensitivity of the assay was 5 ng/ml.

Serum INHA concentration was determined using a two-site ELISA, which was developed specifically for bovine/ovine samples [24]. The sensitivity of the assay was improved by using a different biotinylated detection antibody (PPG 14/6) as recently described [25]. This antibody was raised against a synthetic peptide corresponding to amino acid sequence 1–32 of the bovine {alpha}C subunit. The immobilized "capture" antibody (E4; raised against synthetic peptides corresponding to the amino acid sequence 82–114 of the human and ovine ßA subunit) was the same as that employed in the original assay. Sensitivity of the assay was 0.04 pg/tube, and within- and between-plate CVs were both less than 12%. The antibody used in the INHA assay does not cross-react with the bovine inhibin {alpha} subunit pro{alpha}C, recombinant human (rh) INHB (inhibin B, comprised of {alpha} and ßB subunits), rh-INHBA (activin A, comprised of two ßA subunits), rh-INHBB (activin B, comprised of two ßB subunits), or rh-FST (follistatin-288) [25].

Statistical Analysis

Repeatability (range, 0–1, where 1 = perfect) is defined as the proportion of the total variance that could be attributed to animal variance, which is calculated as {sigma}2 animal/{sigma}2 animal + {sigma}2 error [26]. Variance components were estimated using the PROC MIXED model approach of SAS [27].

In study 1, repeatability of maximal numbers of antral follicles 3 mm or greater in diameter during different follicular waves in the same or consecutive estrous cycles or in estrous cycles spaced 3 or 12 mo apart for individuals was determined as explained above. Also, the paired t-test [27] was used to determine if the overall average maximal number of follicles during waves in estrous cycles was significantly (P ≤ 0.05) different compared with that during estrous cycles of the same individuals 3 or 15 mo later.

In study 2, a mixed-model, repeated-measures approach was used to determine whether growth of dominant and subordinate follicles during follicular waves was similar for cattle that consistently had low, intermediate, high, or very high numbers of follicles during waves [27]. The cattle used in parts A and B of study 1 were used for this analysis. Main effects included technician; groups of cattle with low, intermediate, high, or very high maximal number of follicles during waves; lactation status; age of animals; number of follicular waves per estrous cycle; and ovulatory and nonovulatory waves. Dependent variables included maximal follicle number during waves, length of dominance, interval between ovulations, and diameter of the dominant or subordinate follicles at deviation or during dominance. Number of waves subjected to ultrasound analysis per animal was treated as a repeated measure across individual cows for analyses. Least-squares means were calculated for all main effects in the model.

In study 3, repeatability of maximal numbers of follicles during waves in the three synchronization periods was determined as explained above. A mixed-model, repeated-measures approach was used to determine if serum FSH, estradiol, IGF-I, and INHA concentrations and number of antral follicles were different for cows with low versus cows with very high numbers of follicles during waves [27]. Main effects included groups of cows with low or very high numbers of follicles during waves, time, and an interaction of the follicle groups with time. Serum hormone concentrations and number of follicles were considered to be dependent variables. Time of blood sampling and number of follicles during waves per animal were treated as a repeated measure across individual cows. Data were log10-transformed before statistical analysis. Least-squares means and SEMs of nontransformed data were calculated for all main effects in the model and used to plot the data in Figure 2.



View larger version (22K):
[in this window]
[in a new window]
  		FIG. 2. Number of follicles and serum concentrations of FSH, INHA, and estradiol for Holstein cows that consistently had low (n ≤ 15 follicles, n = 3 cows) versus cows with very high (n > 25 follicles, n = 4 cows) peak numbers of follicles 3 mm or greater in diameter during follicular waves. Symbols represent the average ± SEM for the total number of antral follicles 3 mm or greater in diameter in both ovaries (A) or serum FSH (B), inhibin A (C), or estradiol concentrations (D), respectively, for cows with low (solid circles) versus cows with very high (open circles) numbers of follicles during waves. Data were aligned for statistical analysis relative to the peak of the first postovulatory FSH surge. The arrows in A indicate average times of ovulation, emergence of the first nonovulatory follicular wave, and deviation in growth of dominant versus the largest subordinate follicles (not shown). Follicle number and hormone values at 30, 54 and 78 h after the peak of the postovulatory FSH surge represent pooled values as explained in Results

When main effects were significant (P < 0.05) in study 2 or 3, a Bonferroni t-test was used to determine whether statistical differences existed among individual means [27].


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Study 1: Variability and Repeatability of Number of Follicles 3 mm or Greater in Diameter During Follicular Waves among and Within Individual Cattle

In part A, numbers of follicles during waves for four representative cows that consistently had low, intermediate, high, or very high numbers of follicles during the different follicular waves in an estrous cycle are depicted in Figure 1. These results typified the remarkable similarity in the maximal number of follicles during different follicular waves of individual animals and the great variation among animals. Despite the high variability in maximal number of follicles during waves among cattle (range, 11–54 follicles), repeatability of the maximal number of follicles during different follicular waves in the same or consecutive estrus cycles within each individual was very high overall (0.95; n = 98 follicular waves, 30 animals).



View larger version (43K):
[in this window]
[in a new window]
  		FIG. 1. Differences in total number of antral follicles (diameter, ≥3 mm) during the first and ovulatory follicular waves of an estrous cycle and during the early stages of the first follicular wave of the next estrous cycle of Holstein cows with low (n ≤ 15), intermediate (n = 16–20), high (n = 21–25), or very high (n > 25) numbers of follicles during follicular waves. Each bar represents the average for the total number of follicles in both ovaries determined at each of two daily ultrasound sessions (0800 and 1800 h). An asterisk above a bar indicates maximal number of follicles during each wave. Arrows indicate ovulation. Lines represent changes in diameter of the dominant and the largest subordinate follicle for the first and ovulatory wave. DNF, Dominant nonovulatory follicle (large open circles); DOF, dominant ovulatory follicle (large solid circles); SF, largest subordinate follicle (small open or solid circles)

In part B, a separate study by another ultrasound operator (F.J.-K.), the maximal number of follicles during waves for five animals ranged from 9 to 39 (n = 18 waves). Repeatability of numbers of follicles during waves for individuals was 0.86.

In part C, for estrous cycles 3 mo apart, the maximal number of follicles during waves ranged from 9 to 33 (n = 21 waves) among animals. Repeatability of the maximal number of follicles during waves was 0.92 in individuals, and the overall means ± SEMs for the maximal number of follicles during waves were similar (20.4 ± 1.9 vs. 21.2 ± 2.3, P > 0.20). For estrous cycles 15 mo apart, the maximal number of follicles during waves ranged from 9 to 36 (n = 53 waves) among animals, and repeatability of the maximal number of follicles during waves was 0.85. However, in contrast to estrous cycles spaced 3 mo apart, the overall mean for the maximal number of follicles during waves was 22% lower (P < 0.01) during estrous cycles of cows compared with the same individuals as heifers (16.4 ± 1 vs. 21.1 ± 1). The decrease in maximal numbers of follicles during waves for each of the seven cows compared with the same individuals as heifers was significant (P < 0.05– 0.01) for five animals (15%, 20%, 24%, 40%, and 46%) but not for the others (0% and 12%).

Regarding overall follicular dynamics and variability and repeatability of maximal numbers of follicles 3 mm or greater in diameter during follicular waves, when the 35 animals in parts A and B were combined, seven (four cows, three heifers) had three follicular waves, whereas 28 (14 cows, 14 heifers) had two follicular waves during an estrous cycle. Others [28–30] also report that most Holsteins have two rather than three waves during estrous cycles. The maximal number of follicles during follicular waves averaged 21.5 ± 0.8 (range, 8–54 follicles) and was similar (P > 0.20) for heifers (20 ± 1.1; range, 8–42 follicles; n = 17 animals) and cows (22.8 ± 1.3; range, = 11–54; n = 18). Nevertheless, as previously reported [31] (also see the summary of 15 studies by Sartori et al. [30]), cows had longer (P < 0.05) intervals between ovulations (23.7 ± 0.6 vs. 21.3 ± 0.8 days), larger (P < 0.05) dominant follicles (15.8 ± 0.3 vs. 14.7 ± 0.5 mm) and longer (P < 0.05) periods of dominance (7.6 ± 0.3 vs. 6 ± 0.6 days) compared with heifers.

When animals in parts A and B of study 1 and of study 3 (described below) were combined (n = 44 animals, 138 waves), maximal number of follicles during waves ranged from 8 to 54 among animals, whereas repeatability of maximal number of follicles during waves for individuals was 0.95 (Table 1). In addition, repeatability of maximal number of follicles during waves in individuals was very high (0.86–0.96) regardless of season of year, number of follicular waves per estrous cycle, stage of lactation, technician who conducted the ultrasound examination, or age of cattle (Table 1). Repeatability of basal or the minimal numbers of antral follicles 3 mm or greater in diameter during waves in individuals (range, 2–31) also was high overall (0.85; n = 68 waves, 30 animals).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Effect of various parameters on repeatability of maximal numbers of antral follicles (≥3 mm in diameter) during follicular waves.a

Although follicle diameters ranged from 3 to 20 mm during follicular waves, the vast majority of the total number of follicles counted on most days during waves for each animal had diameters between 3 and 3.9 mm (data not shown). For example, the peak number of follicles in the 3- to 3.9-mm category during waves was at least three- to fivefold greater than the peak number of follicles in any other size categories. Thus, differences in numbers of follicles during waves among cattle (Fig. 1 and Table 1) were primarily the result of differences in numbers of 3-mm follicles.

Study 2: Relationship of Number of Follicles 3 mm or Greater in Diameter During Waves and Development Dynamics of Dominant and Subordinate Follicles

The numbers of heifers or cows with two or three follicular waves per estrous cycle were equally distributed (P > 0.10) in the low, intermediate, high, or very high classifications for number of antral follicles during waves (data not shown).

Age of cattle, stage of lactation, length of dominance, interval between ovulations, day of emergence, day of deviation, largest diameter of the dominant and subordinate follicles during dominance, and diameter of the dominant and subordinate follicles at deviation were similar (P > 0.10) for cattle with low, intermediate, high, or very high numbers of follicles during waves (data not shown).

Study 3: Association of Patterns of FSH, Estradiol, INHA, and IGF-I Secretion with Number of Follicles 3 mm or Greater in Diameter During Follicular Waves

The three cows in the low group averaged 15.1 ± 0.9 follicles during waves (n = 9 follicular waves; range, 11– 18; age, 3 yr), whereas the four cows in the high group averaged 34.9 ± 1.1 follicles during waves (n = 10 follicular waves; range, 29–44; ages, 3–4 yr). Repeatability of maximal number of follicles during waves in three consecutive estrous cycles was very high for individuals (0.90; n = 19 waves, 7 cows) and similar to the results of study 1.

For statistical analysis, all values for numbers of follicles and hormone or growth factor concentrations were aligned for each cow relative to the peak FSH value during the first postovulatory FSH surge. Hereafter, this peak FSH value (t = 0 on the x-axis in Fig. 2) is referred to as the peak of the postovulatory FSH surge. Because of limited numbers of observations (n = 0–2) per time point, values for follicle numbers or each hormone from 20 to 40 h (pool 1), 44 to 64 h (pool 2), and 68 to 88 h (pool 3) after the peak of the postovulatory FSH surge were pooled for each animal. The midway point for each of the aforementioned blood-sampling periods for pool 1, 2, or 3 is depicted along the x-axis in Figure 2 at 30, 54, and 78 h, respectively.

Although serum LH concentrations were not determined in the present study, timing of the preovulatory LH surge was assumed to be coincident with the peak FSH value occurring 20 ± 0 h before the peak of the postovulatory FSH surge (Fig. 2B), which is similar to results of others [25]. Time of ovulation (estimated to be midway between the time of the ultrasound analysis at which the dominant ovulatory follicle was last observed until it was no longer observed) and emergence of the first nonovulatory follicular wave occurred 8.6 ± 2 and 2.3 ± 3 h, respectively, before the peak of the postovulatory FSH surge, whereas deviation and development of the first-wave dominant nonovulatory follicle occurred 41 ± 5.6 h after the peak of the postovulatory FSH surge (Fig. 2A, arrows). No differences were observed in the aforementioned values when cows with low versus cows with very high numbers of follicles during waves were compared. Numbers of follicles during waves were greater (P < 0.001) (Fig. 2A), whereas FSH was lower (P < 0.02) (Fig. 2B) throughout the sampling period for cows with very high versus cows with low numbers of follicles during waves. The INHA level tended to be higher (P < 0.07) (Fig. 2C) primarily before ovulation for cows with very high versus cows with low numbers of follicles during waves. Cows with low versus cows with very high numbers of follicles during waves had similar (P > 0.50) serum concentrations of estradiol (Fig. 2D) and IGF-I (data not shown). During the sampling period, the number of follicles (P < 0.01) increased from 48 to 0 h before the peak of the first postovulatory FSH surge and then declined thereafter (Fig. 2A). In contrast, serum concentrations of FSH (P < 0.001) (Fig. 2B), INHA (P < 0.02) (Fig. 2C), and estradiol (P < 0.001) (Fig. 2D) decreased from 48 h to approximately 24 h before the peak of the postovulatory FSH surge and then increased thereafter. Serum IGF-I concentrations remained unchanged (P > 0.70, data not shown) during the sampling period.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The remarkably high repeatability of the numbers of antral follicles 3 mm or greater in diameter during follicular waves in individual dairy cattle observed in the present study is indirectly supported by the results of other investigators. For example, numbers of 2- to 6-mm follicles at emergence for two successive follicular waves in individual lactating beef cows are highly positively correlated (r = 0.77) [5]. Numbers of growing antral follicles following serial ultrasound-guided needle aspiration of antral follicles every 7–10 days are repeatable (0.58) in individual cattle [26], and numbers of antral follicles are moderately reproducible in individual human beings from one menstrual cycle to the next [32]. The high repeatability of antral follicle growth probably explains why the overall average for maximal number of antral follicles during waves was similar for young compared to older animals in the present study, despite the permanent and steep loss of follicles as cattle age [1]. Indeed, previous reports indicate that the number of antral follicles in ovaries remains relatively constant until cattle are 8 to 10 yr of age [1, 33] and until humans are 35 to 40 yr of age [32]. Thereafter, coincident with the near exhaustion of primordial follicles, the number of antral follicles decrease in cattle [1] and humans [32]. Taken together, these observations indicate that a chronic compensatory mechanism must exist to maintain the high repeatability of numbers of follicles 3 mm or greater in diameter during follicular waves as cattle age. This compensatory mechanism could explain why classical histological studies in several species [34–38] show that the rate of initiation of growth of primordial follicles is inversely associated with the number of growing follicles. For example, the rate of initiation of growth of primordial follicles (recruitment) may have to increase as the ovarian reserve dwindles during aging to maintain a constant number of antral follicles during follicular waves. It is unknown, however, whether this putative chronic compensatory mechanism is similar to the acute compensatory mechanism that maintains the species-specific ovulation rate after unilateral ovariectomy of multiple-ovulating species [39, 40] or has a role in fertility or reproductive longevity.

The maximal number of follicles 3 mm or greater in diameter during waves was slightly, but significantly, lower in the nearly 2-yr-old cows at their peak stages of lactation compared with the same individuals as 10- to 12-mo-old heifers in the present study. We interpret these seemingly contradictory results to indicate that although follicle numbers during waves are highly repeatable in individuals, different physiological states, such as lactation [41], heat stress [42], pregnancy [43], and/or inadequate nutrition [41], may transiently suppress numbers of follicles during waves. The physiological significance and causes of temporary declines in number of follicles during waves, however, are unknown.

Our findings imply that the marked variation among cattle, primarily in number of 3-mm follicles during follicular waves, does not affect development or function of dominant follicles. However, dominant follicle development and secretion of FSH, estradiol, INHA, and IGF-I were not evaluated throughout the ovulatory wave or during the portion of the first nonovulatory follicular wave when estradiol secretion is maximal [9]. Nevertheless, INHA concentrations tended to be higher in cows with very high versus cows with low numbers of follicles during waves on the last day of development of ovulatory follicles, but not during the first nonovulatory follicular wave. This observation supports the possibility that the number of follicles during waves may influence, or be associated with, alterations in the secretion of growth factors by dominant follicles. It also suggests that small antral follicles make a significant contribution to circulating INHA levels. Further studies will be necessary to determine if the variation in number of follicles during follicular waves is associated with alterations in dominant follicle function.

The general patterns of secretion of FSH, estradiol, and INHA during the later stages of development of the dominant ovulatory follicle and during the early stages of development of the first nonovulatory follicular wave are similar to previous reports for cattle [9, 25, 44, 45]. However, concentrations of FSH were inversely, rather than positively, associated with the number of follicles 3 mm or greater in diameter during follicular waves in the present study, as recently reported for dairy heifers [46] and lactating beef cows [5]. Although estradiol and INHA would be expected to be produced primarily by the largest antral follicles during waves [47], it was somewhat surprising that serum concentrations of these negative-feedback hormones were similar for cows with low versus cows with very high numbers of follicles during waves. This observation supports the speculation that factors other than FSH and its chief negative-feedback hormones, estradiol and INHA, have a role in regulating the number of follicles growing during waves. For example, despite treatment of cattle with a GNRH1 agonist to significantly reduce secretion of FSH and LH [48], antral follicles grow to at least 4 mm in diameter. Growth hormone [49] and IGF-I [50] promote growth of antral follicles. Thus, alterations in secretion of either of these hormones could explain the high variability, primarily in number of 3-mm follicles, during waves among the cattle in the present study. Nevertheless, serum IGF-I concentrations were similar for cows with very high versus cows with low numbers of follicles during waves in the present study, implying that other mechanisms, such as size of the ovarian reserve, may regulate the variation in numbers of follicles during follicular waves.

Indirect evidence indicates that the number of follicles during follicular waves probably reflects the size of the ovarian reserve in humans [32, 51] and cattle [1, 3, 52]. Thus, the cattle with high serum FSH concentrations and relatively low numbers of follicles during waves in the present study also may have had relatively smaller ovarian reserves. In support of this possibility, serum FSH is higher in older women [53] and cows [54] compared to their younger counterparts. Factors that regulate variation in antral follicle numbers during waves may include not only size of the ovarian reserve, differential responsiveness of antral follicles to FSH [55], differential secretion of hormones and growth factors that alter FSH responsiveness (e.g., LH [56]), and genetic mechanisms [52, 55] but also growth factors that regulate recruitment and growth of preantral follicles, such as antimullerian hormone [57–59], KIT ligand [60, 61], INHBA [62], and growth differentiation factor 9 [60, 63, 64]. Moreover, our findings imply that estradiol and INHA may not be the only feedback regulators of FSH secretion during follicular waves. Rather, control of FSH secretion during follicular waves may involve other follicular (or intrapituitary) factors, such as INHBA, which stimulate FSH secretion; FST, which inhibits INHBA action; or inhibin B, which inhibits FSH secretion [15]. In addition, differential secretion of GNRH1, differential sensitivity to GNRH1 or to the negative feedback actions of INHA, and/or estradiol could explain our results. Most importantly, the high repeatability of the number of follicles 3 mm or greater in diameter during waves of individuals, coupled with the high variation in follicular number among cattle, enables use of ultrasound to identify reliably groups of cattle that consistently have low, intermediate, high, or very high numbers of follicles during waves. Consequently, classification of cattle based on the number of antral follicles 3 mm or greater in diameter during waves should provide a novel model not only to elucidate the potentially complex role of the aforementioned factors in regulation of FSH secretion and the dynamics of follicular growth but also to examine the relationship of the variation in numbers of follicles during waves among cattle to size of the ovarian reserve, reproductive life span, superovulation, and fertility.

We conclude the following: First, despite an approximately sevenfold variation in maximal number of follicles 3 mm or greater in diameter during waves among cattle, development of two or three follicular waves in different hormonal milieus during estrous cycles, and a decline in the number of antral follicles during waves in association with aging and lactation, a compensatory mechanism exists to maintain a very highly repeatable (0.95) number of follicles during waves in estrous cycles of individuals. Second, variation in the numbers of follicles 3 mm or greater in diameter during waves and the inverse association of the number of follicles during waves with FSH are not directly explained by alterations in the secretion patterns of estradiol, INHA, or IGF-I. Third, use of ultrasound to identify cattle with consistently low or high numbers of follicles 3 mm or greater in diameter during waves provides a novel experimental model to determine the causes and physiological significance of the high variation in follicle number during follicular waves among single-ovulating species, such as cattle and humans.


   ACKNOWLEDGMENTS
 
We thank Drs. George Smith and Kathy Ernst for their helpful comments in preparation of this manuscript.


   FOOTNOTES
 
1 Supported by National Research Initiative Competitive grants 2000-02391, 2001-02255, and 2004-01697 from the USDA Cooperative State Research, Education, and Extension Service and by funds from the Agricultural Experiment Station at Michigan State University to J.J.I. Back

2 Correspondence. FAX: 517-353-3149; Ireland{at}msu.edu Back

Received: 5 October 2004.

First decision: 29 October 2004.

Accepted: 22 February 2005.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Erickson BH. Development and senescence of the postnatal bovine ovary. J Anim Sci 1966 25:800-805
  2. Kawamata M. Relationship between the number of small follicles prior to superovulatory treatment and superovulatory response in Holstein cows. J Vet Med Sci 1994 56:965-970[Medline]
  3. Cushman RA, DeSouza JC, Hedgpeth VS, Britt JH. Superovulatory response of one ovary is related to the micro- and macroscopic population of follicles in the contralateral ovary of the cow. Biol Reprod 1999 60:349-354[Abstract/Free Full Text]
  4. Taneja M, Bols PE, Van de Velde A, Ju JC, Schreiber D, Tripp MW, Levine H, Echelard Y, Riesen J, Yang X. Developmental competence of juvenile calf oocytes in vitro and in vivo: influence of donor animal variation and repeated gonadotropin stimulation. Biol Reprod 2000 62:206-213[Abstract/Free Full Text]
  5. Singh J, Dominguez M, Jaiswal R, Adams GP. A simple ultrasound test to predict the superstimulatory response in cattle. Theriogenology 2004 62:227-243[CrossRef][Medline]
  6. Oliveira JF, Neves JP, Moraes JC, Goncalves PB, Bahr JM, Hernandez AG, Costa LF. Follicular development and steroid concentrations in cows with different levels of fertility raised under nutritional stress. Anim Reprod Sci 2002 73:1-10[CrossRef][Medline]
  7. Erickson BH, Reynolds RA, Murphree RL. Ovarian characteristics and reproductive performance in aged cows. Biol Reprod 1976 15:555-560[Abstract]
  8. Adams GP, Matteri RL, Kastelic JP, Ko JC, Ginther OJ. Association between surges of follicle-stimulating hormone and the emergence of follicular waves in heifers. J Reprod Fertil 1992 94:177-188
  9. Sunderland SJ, Crowe MA, Boland MP, Roche JF, Ireland JJ. Selection, dominance and atresia of follicles during the estrous cycle of heifers. J Reprod Fertil 1994 101:547-555
  10. Evans ACO, Adams GP, Rawlings NC. Endocrine and ovarian follicular changes leading up to the first ovulation in prepubertal heifers. J Reprod Fertil 1994 100:187-194
  11. Ginther OJ, Wiltbank MC, Fricke PM, Gibbons JR, Kot K. Selection of the dominant follicle in cattle. Biol Reprod 1996 55:1187-1194[CrossRef][Medline]
  12. Ireland JJ, Mihm M, Austin E, Diskin MG, Roche JF. Historical perspective of turnover of dominant follicles during the bovine estrous cycle: key concepts, studies, advancements, and terms. J Dairy Sci 2000 83:1648-1658[Abstract]
  13. Fortune JE. Ovarian follicular growth and development in mammals. Biol Reprod 1994 50:225-232[Abstract]
  14. Turzillo AM, Fortune JE. Suppression of the secondary FSH surge with bovine follicular fluid is associated with delayed ovarian follicular development in heifers. J Reprod Fertil 1990 89:643-653
  15. Knight PG. Roles of inhibins, activins, and follistatin in the female reproductive system. Front Neuroendocrinol 1996 17:476-509[CrossRef][Medline]
  16. Padmanabhan V, Karsch FJ, Lee JS. Hypothalamic, pituitary, and gonadal regulation of FSH. Reprod Suppl 2002 59:67-82[Medline]
  17. Richards JS. Hormonal control of gene expression in the ovary. Endocr Rev 1994 15:725-751[CrossRef][Medline]
  18. Zhou J, Kumar TR, Matzuk MM, Bondy C. Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary. Mol Endocrinol 1997 11:1924-1933[Abstract/Free Full Text]
  19. Gutierrez CG, Campbell BK, Webb R. Development of a long-term bovine granulosa cell culture system: induction and maintenance of estradiol production, response to follicle-stimulating hormone, and morphological characteristics. Biol Reprod 1997 56:608-616[Abstract]
  20. Bame JH, Dalton JC, Degelos SD, Good TE, Ireland JL, Jimenez-Krassel F, Sweeney T, Saacke RG, Ireland JJ. Effect of long-term immunization against inhibin on sperm output in bulls. Biol Reprod 1999 60:1360-1366[Abstract/Free Full Text]
  21. Crowe MA, Padmanabhan V, Hynes N, Sunderland SJ, Enright WJ, Beitins IZ, Roche JF. Validation of a sensitive radioimmunoassay to measure serum follicle-stimulating hormone in cattle: correlation with biological activity. Anim Reprod Sci 1997 48:123-136[CrossRef][Medline]
  22. Prendiville DJ, Enright WJ, Crowe MA, Finnerty M, Hynes H, Roche JF. Immunization of heifers against gonadotropin-releasing hormone: antibody titers, ovarian function, body growth, and carcass characteristics. J Anim Sci 1995 73:2382-2389[Abstract]
  23. Greenwood RH, Titgemeyer EC, Stokka GL, Drouillard JS, Löest CA. Effects of L-carnitine on nitrogen retention and blood metabolites of growing steers and performance of finishing steers. J Anim Sci 2001 79:254-260[Abstract/Free Full Text]
  24. Knight PG, Feist SA, Tannetta DS, Bleach ECL, Fowler PA, O'Brien M, Groome NP. Measurement of inhibin A ({alpha}ßA dimer) during the estrous cycle, after manipulation of ovarian activity and during pregnancy in ewes. J Reprod Fertil 1998 113:159-166
  25. Bleach ECL, Glencross RG, Feist SA, Groome NP, Knight PG. Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid. Biol Reprod 2001 64:743-752[Abstract/Free Full Text]
  26. Boni R, Roelofsen M, Pieterse M, Kogut J, Kruip T. Follicular dynamics: repeatability and predictability of follicular recruitment in cows undergoing repeated follicular puncture. Theriogenology 1997 48:277-289
  27. SAS User's Guide: Statistics. Cary, NC: SAS Institute, Inc.; 1995
  28. Ginther OJ, Knopf L, Kastelic JP. Temporal associations among ovarian events in cattle during estrous cycles with two and three follicular waves. J Reprod Fertil 1989 87:223-230
  29. Townson DH, Tsang PCW, Butler WR, Frajblat M, Griel LC Jr, Johnson CJ, Milvae RA, Niksic GM, Pate JL. Relationship of fertility to ovarian follicular waves before breeding in dairy cows. J Anim Sci 2002 80:1053-1058[Abstract/Free Full Text]
  30. Sartori R, Haughian JM, Shaver RD, Rosa GJM, Wiltbank MC. Comparison of ovarian function and circulating steroids in estrous cycles of Holstein heifers and lactating cows. J Dairy Sci 2004 87:905-920[Abstract/Free Full Text]
  31. Wolfenson D, Inbar G, Roth Z, Kaim M, Bloch A, Braw-Tal R. Follicular dynamics and concentrations of steroids and gonadotropins in lactating cows and nulliparous heifers. Theriogenology 2004 62:1042-1055[CrossRef][Medline]
  32. Scheffer GJ, Broekmans FJ, Dorland M, Habbema JD, Looman CW, te Velde ER. Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility. Fertil Steril 1999 72:845-851[CrossRef][Medline]
  33. Katska L, Smorag Z. Number and quality of oocytes in relation to age in cattle. Anim Reprod Sci 1984 7:451-460[CrossRef]
  34. Krarup T, Pederson T, Faber M. Regulation of oocyte growth in the mouse ovary. Nature 1969 224:187-188[CrossRef][Medline]
  35. Peters H, Byskov AG, Grinsted J. Follicular growth in fetal and prepubertal ovaries of humans and other primates. Clin Endocrinol Metab 1978 7:469-485[CrossRef][Medline]
  36. Driancourt MA. Ovarian features contributing to the variability of PMSG-induced ovulation rate in sheep. J Reprod Fertil 1987 80:207-212
  37. Hirshfield AN. Relationship between supply of primordial follicles and the onset of follicular growth in rats. Biol Reprod 1994 50:421-428[Abstract]
  38. Shirota M, Soda S, Katoh C, Asai S, Sato M, Ohta R, Watanabe G, Taya K, Shirota K. Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats. Reproduction 2003 125:85-94[Abstract]
  39. Hermreck AS, Greenwald GS. The effects of unilateral ovariectomy on follicular maturation in the guinea pig. Anat Rec 1964 148:171-176[CrossRef][Medline]
  40. King BF, Britt JH, Esbenshade KL, Flowers WL, Ireland JJ. Evidence for a local role of inhibin or inhibin {alpha} subunits in compensatory ovarian hypertrophy. J Reprod Fertil 1995 104:291-295
  41. Lucy MC, Staples CR, Michel FM, Thatcher WW. Energy balance and size and number of ovarian follicles detected by ultrasonography in early postpartum dairy cows. J Dairy Sci 1991 74:473-482[Abstract]
  42. Wolfenson D, Thatcher WW, Badinga L, Savio JD, Meidan R, Lew BJ, Braw-Tal R, Berman A. Effect of heat stress on follicular development during the estrous cycle in lactating dairy cattle. Biol Reprod 1995 52:1106-1113[Abstract]
  43. Ginther OJ, Kot K, Kulick LJ, Martin SJ, Wiltbank MC. Relationships between FSH and ovarian follicular waves during the last six months of pregnancy in cattle. J Reprod Fertil 1996 108:271-290
  44. Mihm M, Good TE, Ireland JL, Ireland JJ, Knight PG, Roche JF. Decline in serum follicle-stimulating hormone concentrations alters key intrafollicular growth factors involved in selection of the dominant follicle in heifers. Biol Reprod 1997 57:1328-1337[Abstract]
  45. Kaneko H, Noguchi J, Kikuchi K, Todoroki J, Hasegawa Y. Alterations in peripheral concentrations of inhibin A in cattle studied using a time-resolved immunofluorometric assay: relationship with estradiol and follicle-stimulating hormone in various reproductive conditions. Biol Reprod 2002 67:38-45[Abstract/Free Full Text]
  46. Haughian JM, Ginther OJ, Kot K, Wiltbank MC. Relationship between FSH patterns and follicular dynamics and the temporal associations among hormones in natural and GnRH-induced gonadotropin surges in heifers. Reproduction 2004 127:23-33[Abstract/Free Full Text]
  47. Austin EJ, Mihm M, Evans ACO, Knight PG, Ireland JLH, Ireland JJ, Roche JF. Alterations in intrafollicular regulatory factors and apoptosis during selection of follicles in the first follicular wave of the bovine estrous cycle. Biol Reprod 2001 64:839-848[Abstract/Free Full Text]
  48. Gong JG, Campbell BK, Bramley TA, Gutierrez CG, Peters AR, Webb R. Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist. Biol Reprod 1996 55:68-74[Abstract]
  49. Gong JG, Bramley TA, Webb R. The effect of recombinant bovine somatotrophin on ovarian follicular growth and development in heifers. J Reprod Fertil 1993 97:247-254
  50. Campbell BK, Scaramuzzi RJ, Webb R. Control of antral follicle development and selection in sheep and cattle. J Reprod Fertil Suppl 1995 49:335-350[Medline]
  51. Scheffer GJ, Broekmans FJ, Looman CW, Blankenstein M, Fauser BC, de Jong FH, te Velde ER. The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod 2003 18:700-706[Abstract/Free Full Text]
  52. Cushman RA, Hedgpeth VS, Echternkamp SE, Britt JH. Evaluation of numbers of microscopic and macroscopic follicles in cattle selected for twinning. J Anim Sci 2000 78:1564-1567[Abstract/Free Full Text]
  53. Klein NA, Battaglia DE, Fujimoto VY, Davis GS, Bremner WJ, Soules MR. Reproductive aging: accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women. J Clin Endocrinol Metab 1996 81:1038-1045[Abstract]
  54. Bryner RW, Garcia-Winder M, Lewis PE, Inskeep EK, Butcher RL. Changes in hormonal profiles during the estrous cycle in old lactating beef cows. Domest Anim Endocrinol 1990 7:181-190[CrossRef][Medline]
  55. Spearow JL, Bradford GE. Genetic variation in spontaneous ovulation rate and LH receptor induction in mice. J Reprod Fertil 1983 69:529-537
  56. Richards JS, Ireland JJ, Rao MC, Bernath GA, Midgley AR Jr, Reichert LE Jr. Ovarian follicular development in the rat: hormone-receptor regulation by estradiol, follicle stimulating hormone, and luteinizing hormone. Endocrinology 1976 99:1562-1570[Abstract]
  57. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, Themmen AP. Control of primordial follicle recruitment by anti-mullerian hormone in the mouse ovary. Endocrinology 1999 140:5789-5796[Abstract/Free Full Text]
  58. McGee EA, Smith R, Spears N, Nachtigal MW, Ingraham H, Hsueh AJ. Mullerian inhibitory substance induces growth of rat preantral ovarian follicles. Biol Reprod 2001 64:293-298[Abstract/Free Full Text]
  59. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Kumar TR, Matzuk MM, Rose UM, de Jong FH, Uilenbroek JT, Grootegoed JA, Themmen AP. Anti-mullerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 2001 142:4891-4899[Abstract/Free Full Text]
  60. Hsueh AJ, McGee EA, Hayashi M, Hsu SY. Hormonal regulation of early follicle development in the rat ovary. Mol Cell Endocrinol 2000 163:95-100[CrossRef][Medline]
  61. Reynaud K, Cortvrindt R, Smitz J, Bernex F, Panthier JJ, Driancourt MA. Alterations in ovarian function of mice with reduced amounts of KIT receptor. Reproduction 2001 121:229-237[Abstract]
  62. Liu X, Andoh K, Yokota H, Kobayashi J, Abe Y, Yamada K, Mizunuma H, Ibuki Y. Effects of growth hormone, activin, and follistatin on the development of preantral follicle from immature female mice. Endocrinology 1998 139:2342-2347[Abstract/Free Full Text]
  63. Carabatsos MJ, Elvin J, Matzuk MM, Albertini DF. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol 1998 204:373-384[CrossRef][Medline]
  64. Juengel JL, Hudson NL, Heath DA, Smith P, Reader KL, Lawrence SB, O'Connell AR, Laitinen MPE, Cranfield M, Groome NP, Ritvos O, McNatty KP. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol Reprod 2002 67:1777-1789[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Biol. Reprod.Home page
D. Monniaux, N. d. Clemente, J.-L. Touze, C. Belville, C. Rico, M. Bontoux, J.-Y. Picard, and S. Fabre
Intrafollicular Steroids and Anti-Mullerian Hormone During Normal and Cystic Ovarian Follicular Development in the Cow
Biol Reprod, August 1, 2008; 79(2): 387 - 396.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
P. S Malhi, G. P Adams, R. J Mapletoft, and J. Singh
Oocyte developmental competence in a bovine model of reproductive aging
Reproduction, August 1, 2007; 134(2): 233 - 239.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
JJ. Ireland, F. Ward, F. Jimenez-Krassel, J.L.H. Ireland, G.W. Smith, P. Lonergan, and A.C.O. Evans
Follicle numbers are highly repeatable within individual animals but are inversely correlated with FSH concentrations and the proportion of good-quality embryos after ovarian stimulation in cattle
Hum. Reprod., June 1, 2007; 22(6): 1687 - 1695.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
N. M. Bello, J. P. Steibel, and J. R. Pursley
Optimizing ovulation to first GnRH improved outcomes to each hormonal injection of ovsynch in lactating dairy cows.
J Dairy Sci, September 1, 2006; 89(9): 3413 - 3424.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
73/1/54    most recent
biolreprod.104.036277v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal