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BOR - Papers in Press, published online ahead of print March 19, 2003.
Biol Reprod 2003, 10.1095/biolreprod.102.012179
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BIOLOGY OF REPRODUCTION 69, 218–223 (2003)
DOI: 10.1095/biolreprod.102.012179
© 2003 by the Society for the Study of Reproduction, Inc.

Ovary

Relationship Between Endogenous Progesterone and Follicular Dynamics in Lactating Dairy Cows with Ovarian Follicular Cysts1

T.B. Hatler, S.H. Hayes, L.F. Laranja da Fonseca, and W.J. Silvia2

Animal Sciences Department, University of Kentucky, Lexington, Kentucky 40506-0033


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Two experiments were conducted to examine circulating concentrations of progesterone (P4) in cows with ovarian follicular cysts (OFCs) and to relate differing levels of P4 to subsequent follicular events. In experiment 1, peripheral concentrations of P4 were determined in cows diagnosed with OFCs. Nonpregnant, lactating Holstein and Jersey cows (n = 32) were diagnosed as having OFCs by rectal palpation. Ovarian follicular cysts were then examined by transrectal ultrasonography to confirm the presence of OFCs (follicle diameter, ≥17 mm; absence of luteal tissue). At confirmation, a blood sample was collected for quantification of P4. The concentration of P4 at confirmation was classified as low (<0.1 ng/ml), intermediate (0.1–1.0 ng/ml), or high (1.0–2.0 ng/ml). More OFCs were associated with intermediate (66%) than with either low (28%) or high (6%) concentrations of P4. In experiment 2, the fate of follicles (diameter, ≥10 mm) that formed in the presence of an OFC was determined and related to circulating concentrations of P4 during follicular development. Follicles (n = 59) that formed in the presence of an OFC ovulated (n = 19), formed a cyst (n = 30), or underwent normal growth and regression (NGR; n = 10). Endogenous P4 in the 7-day period during follicular development was classified as low (if P4 dropped to <0.1 ng/ml for 1 day or longer), intermediate (if P4 averaged between 0.1 and 1.0 ng/ml and never dropped to <0.1 ng/ml), or high (if P4 averaged >1.0 ng/ml and never dropped to <0.1 ng/ml). In the presence of intermediate P4, 75% of observed follicles formed cysts, compared with 10% that ovulated and 15% that experienced NGR. In the presence of low P4, 53%, 41%, and 6% of follicles ovulated, formed a follicular cyst, or experienced NGR, respectively. Thus, an association between intermediate P4 and the formation of OFCs was established.

follicle, lactation, ovary, ovulation, progesterone


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Ovarian follicular cysts are aberrant follicular structures that reach ovulatory size, fail to ovulate, and alter normal ovarian cyclicity. Cysts are a major contributor to reduced reproductive efficiency of lactating dairy cows. The incidence of ovarian follicular cysts in dairy cattle has been reported to be from 5.6% to 18.8% [1]. Each incidence of ovarian follicular cyst formation increases the calving interval by 22–64 days [2, 3].

Traditionally, cysts have been defined as anovulatory, follicular structures (diameter, >25 mm) that persist for 10 or more days in the absence of a functional corpus luteum [1]. However, recent data using ultrasonography indicate that follicles typically ovulate at 17 mm in diameter, so follicles that persist at that diameter or greater may be considered to be "cystic." Eyestone and Ax [4] showed that considerable variability exists among follicular cysts with respect to their steroidogenic capacity. In general, cows with follicular cysts have greater estradiol concentrations in follicular fluid [5] and in the circulation [6–9] than do cows without follicular cysts or with normal follicles.

Cysts appear to form because of an "endocrine imbalance." The vast majority of data suggest that cysts form because of a failure of the preovulatory LH surge to occur at the appropriate time in follicular maturation [10]. Injections of GnRH are able to stimulate the release of an LH surge from the anterior pituitary gland in cows with follicular cysts, indicating that it is functioning normally [11, 12]. In cows with follicular cysts, high endogenous levels of estradiol [10] and estradiol injections [13] are unable to induce a surge of LH. Thus, the positive-feedback mechanism of estradiol on the LH surge may not be functioning properly in cows with follicular cysts. This malfunction appears to reside at the hypothalamic level. Hypothalamic responsiveness to estradiol injections in cows with follicular cysts was restored 6 wk after the removal of ovaries with follicular cysts [14]. This implies that the factor responsible for blocking the LH surge in cows with follicular cysts may be of ovarian origin. Progesterone, an ovarian steroid present in the fluid from follicular cysts [5], may contribute to the cystic condition by blocking the LH surge. Follicular dynamics can be disrupted by administration of progesterone during the follicular phase. If progesterone is administered at intermediate levels (0.5–2 ng/ml), it will block the LH surge, prevent ovulation, and result in formation of a follicle with a greater diameter and persistency than those of normal dominant follicles [15, 16].

The extent to which follicular cysts secrete progesterone is unknown. The fluid from ovarian follicular cysts contains progesterone [5, 17–19]. Peripheral concentrations of progesterone in cows with follicular cysts frequently appear to fall in the intermediate (0.1–1.0 ng/ml) range [10, 20–22]. To our knowledge, the extent to which intermediate concentrations of progesterone may contribute to the formation of ovarian follicular cysts has not been investigated.

The objectives of the present study were to determine how often cows diagnosed with ovarian follicular cysts have intermediate concentrations of progesterone and to relate the fate of follicles that form in the presence of a follicular cyst to circulating concentrations of progesterone during their development.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Experiment 1: Progesterone at Follicular Cyst Confirmation

Ovarian follicular cysts were identified in lactating Holstein and Jersey cows during routine reproductive examinations of the University of Kentucky Dairy Research Herd. Ovaries of all cows in the breeding herd were palpated per rectum at 9- to 14-day intervals for detection of cysts beginning at least 40 days postpartum. Bred cows were also palpated per rectum 50–60 days after breeding for pregnancy determination or cyst detection. When a cyst was diagnosed by palpation, the cystic structure was re-examined by transrectal ultrasonography. For a follicle to be classified as an ovarian follicular cyst, the follicle had to measure at least 17 mm in diameter and be free of tissue that had ecogenic characteristics similar to luteal tissue, and ovaries had to be free of corpora lutea. This size criterion (diameter, ≥17 mm) was chosen because Ginther et al. [23] reported that normal ovulatory follicles in dairy cattle reach an average diameter of 16 ± 0.4 mm or 13.9 ± 0.4 mm at ovulation (two vs. three waves of follicle growth, respectively). In our experience, persistent follicles often fail to reach 25 mm in diameter, which is the diameter traditionally chosen to define cysts. Gümen et al. [24] have reported a similar observation. The absence of luteal tissue on either ovary implied that the cyst was functional at diagnosis and that normal cycles were not occurring.

Once the presence of a follicular cyst was confirmed by transrectal ultrasonography (n = 32 cows), a blood sample was then collected via jugular or coccygeal venipuncture to determine the circulating concentration of progesterone. The concentration of progesterone at cyst confirmation was then classified as low (<0.1 ng/ml), intermediate (0.1–1.0 ng/ml), or high (1.0–2.0 ng/ml). After cyst confirmation, blood samples were collected daily, and ultrasonography of ovaries continued for the next 7 days to ensure that cysts were identified correctly as follicular (cysts maintained a diameter of ≥17 mm) and that ovulation did not occur. If ovulation occurred within 7 days after cyst confirmation, the cow was removed from the experiment.

Differences in the number of cows in each progesterone classification at the day of cyst confirmation were determined by chi-square analysis [25].

Experiment 2: Influence of Progesterone on Follicular Dynamics in Cows with Follicular Cysts

Cows confirmed as having ovarian follicular cysts in experiment 1 were moved to a tie-stall research barn for experiment 2. Cows were fed a lactating cow ration and had free access to water. Cows were milked twice each day and were released from the tie-stall barn into a dirt paddock to receive approximately 3 h of exercise each day.

Ovaries were examined via transrectal ultrasonography between 0800 and 1200 h three times each week (Monday, Wednesday, and Friday). The ultrasound technician would scan each ovary in several different planes to become oriented with the position and size of each follicle/cyst. The technician then measured all dominant follicles (diameter, ≥10 mm) and cysts at their greatest diameter and noted the relative position of each follicle/cyst. After each examination, a diagram of the position and size of each follicle/cyst on each ovary was made. Once data collection from a cow ended, the pattern of growth and regression of individual follicles/cysts was retrospectively identified from the ovarian diagrams made after each ultrasound examination. This method of follicle tracking allowed the growth and regression of an individual follicle/cyst to be mapped. Blood samples were collected daily via jugular or coccygeal venipuncture to quantify circulating concentrations of progesterone. Blood sampling and ultrasonographic procedures were approved by the University of Kentucky Institutional Animal Care and Use Committee.

The fate of follicles (diameter, ≥10 mm) that formed in the presence of an existing ovarian follicular cyst was examined. Follicles were classified into one of three categories: cyst formation, ovulation, or normal follicle growth and regression. Cyst formations were defined as follicles that obtained a diameter of 17 mm or greater and that persisted at that diameter or greater for three or more consecutive ultrasonographic scanning sessions (i.e., 5–6 days). Ovulation was defined as the emergence and then disappearance of a follicle 10 mm or greater in diameter and subsequent corpus luteum formation based on ultrasonographic scanning accompanied by an increase in circulating concentrations of progesterone. Normal follicle growth and regression was defined as a follicle that was detectable for three or more consecutive ultrasonographic imaging sessions (i.e., 5–6 days) and that did not persist or ovulate. Ultrasound scanning and blood sampling ceased once ovulation was confirmed, the cow received treatment to correct the cystic condition, or other management decisions dictated.

For follicles that ovulated in the presence of an ovarian follicular cyst, concentrations of progesterone were examined for the 7-day period before the day of ovulation. For follicles that formed cysts in the presence of an ovarian follicular cyst, concentrations of progesterone were examined for the 7-day period before the first day that the follicle attained a diameter of 17 mm or greater. For follicles that underwent normal growth and regression in the presence of an ovarian follicular cyst, concentrations of progesterone were examined for the 7-day period before the follicle attained maximum diameter. The progesterone environment associated with the development of each follicle in the presence of a follicular cyst was classified into one of three categories. Progesterone was classified as high if the endogenous progesterone level averaged greater than 1.0 ng/ml and never dropped to less than 0.1 ng/ml during the 7-day period. Progesterone was classified as intermediate if the endogenous progesterone level averaged between 0.1 and 1.0 ng/ml and never dropped to less than 0.1 ng/ml during the 7-day period. Progesterone was classified as low if the endogenous progesterone level dropped to less than 0.1 ng/ml for one or more days during the 7-day period. The physiological basis for these classifications was as follows: The presence of a follicular cyst is commonly associated with progesterone levels of less than 1.0 ng/ml [20]. Ovulation typically occurs when progesterone drops to less than 0.1 ng/ml [26]. To our knowledge, the follicular events that occur when progesterone concentrations are between 0.1 and 1.0 ng/ml have not been thoroughly investigated.

Statistics

A chi-square analysis was performed to detect differences in the frequency of the fates of follicles (cyst formation, ovulation, and normal growth and regression) that formed in the presence of an existing follicular cyst. The FREQ procedure of SAS [27] was used to determine if follicle fate and progesterone classification were independent. Chi-square analyses were then performed to detect differences in the frequency of follicle fate (cyst formation, ovulation, or normal growth and regression) within progesterone class (low, intermediate, or high) and in the frequency of follicles in each progesterone class (low, intermediate, or high) within each follicle fate (cyst formation, ovulation, or normal growth and regression).

Ultrasonography and Blood Sampling

Ultrasonographic examinations of ovaries were conducted with a real-time, B-mode instrument equipped with a 7.5-MHz, linear-array intrarectal transducer. Follicle diameter was measured to the nearest 0.1 mm using the internal caliper function of the ultrasound instrument.

Blood samples were collected daily via jugular or coccygeal venipuncture into tubes containing 100 µl of EDTA (6 mg/100 µl for 5 ml of blood). Immediately after collection, samples were centrifuged at 2500 rpm. Plasma was separated and stored in 7 ml scintillation vials at -20°C. Radioimmunoassay was performed using a solid-phase radioimmunoassay kit (Coat-A-Count Progesterone; Diagnostic Products Corporation, Los Angeles, CA) as previously described [28]. Inter- and intraassay coefficients of variation were 12% and 9%, respectively. The sensitivity of the assay was 2.0 pg/assay tube at 95% of maximum binding.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Experiment 1: Progesterone at Follicular Cyst Confirmation

Thirty-two cows were diagnosed as having follicular cysts. The distribution of cows with follicular cysts in the three progesterone categories was not random (P < 0.01) (Fig. 1). Twenty-one of these 32 cows (66%) had plasma concentrations of progesterone that were intermediate (range, 0.1–0.93 ng/ml; average, 0.5 ng/ml) at the time of cyst detection. Nine of the 32 cows (28%) had low plasma progesterone concentrations (range, 0.02–0.08 ng/ml; average, 0.05 ng/ml). Only two cows (6%) had high plasma progesterone concentrations (range, 1.44–1.71 ng/ml; average, 1.58 ng/ml). On average, follicular cysts in cows were first detected at 188 days in lactation (range, 47–343 days). Of the 32 cows diagnosed as having follicular cysts, 17 had only one cyst, 12 had two cysts, and 3 had three cysts on the day of cyst detection.



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  		FIG. 1. Number of cows with serum concentration of progesterone classified as low (<0.1 ng/ml), intermediate (Int; 0.1–1.0 ng/ml), or high (>1.0 ng/ml) at the time of cyst detection. Bars with different letters are significantly different (P < 0.01)

Experiment 2: Influence of Progesterone on Follicular Dynamics in Cows with Follicular Cysts

The fates of 59 follicles that formed in 26 of the cows with follicular cysts from experiment 1 were determined. Thirty-four of these follicles were the first large follicle that formed following initial detection of the cyst. The remaining 25 follicles were from subsequent cohorts that emerged in the presence of either the initial cyst or another cyst that formed later. Fates of the follicles did not occur at equal frequencies (P < 0.01). More follicles formed cysts (30 of 59 [51%]) than experienced normal growth and regression (10 of 59 [17%]; P < 0.01). Ovulation occurred at a frequency that was intermediate (32%) and not significantly different from that of either cyst formation or normal growth and regression.

The fate of follicles that formed in the presence of ovarian follicular cysts was influenced by the concentration of progesterone during the maturation of those follicles. Follicle fate and progesterone classification were not independent (P < 0.01). In the presence of intermediate progesterone (0.1–1.0 ng/ml), the large majority of follicles (15 of 20 [75%]) (Fig. 2, see representative animals in Figs. 3 and 4) formed cysts (P < 0.01). A much smaller number of follicles experienced either normal growth and regression (3 of 20 [15%]) or ovulation (2 of 20 [10%]). This is in contrast to follicles that formed in the presence of low progesterone (<0.1 ng/ml), in which the frequency of ovulation (17 of 32 [53%]) did not differ from that of cyst formation (13 of 32 [41%]). The vast majority of ovulations (17 of 19 is equal to 90%) occurred in this low category of progesterone (P < 0.01) (Fig. 5, see representative animal in Fig. 6). The only exception occurred in one cow classified as intermediate, in which circulating concentrations of progesterone dropped to only 0.12 ng/ml before the cow ovulated two follicles. Ovulation never occurred in the presence of high progesterone (>1.0 ng/ml).



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  		FIG. 2. The number of follicles that formed in the presence of an ovarian follicular cyst that either formed a follicular cyst (Cyst), ovulated (Ov), or experienced normal growth and regression (NGR) in an environment with high (>1.0 ng/ml), intermediate (Int; 0.1–1.0 ng/ml), or low (<0.1 ng/ml) progesterone level. Follicle fate and progesterone classification were not independent (P < 0.01). Bars with different letters within each classification of progesterone (high, intermediate, or low) are significantly different (P < 0.01)



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  		FIG. 3. Diameter of a newly formed follicular cyst ({circ}), of the originally detected cystic follicle ({diamondsuit}), and circulating concentrations of progesterone ({square}) for a representative cow with intermediate progesterone (0.1–1.0 ng/ml) during cyst formation. The first day on which the newly formed cystic follicle reached the cystic diameter (≥17 mm) is indicated ({uparrow})



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  		FIG. 4. Diameter of the newly formed follicular cyst ({circ}), of the originally detected cystic follicle ({diamondsuit}), and circulating concentrations of progesterone ({square}) for a representative cow with intermediate progesterone (0.1–1.0 ng/ml) during cyst formation. The first day on which the newly formed cystic follicle reached the cystic diameter (≥17 mm) is indicated ({uparrow})



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  		FIG. 5. The number of follicles that formed in the presence of an ovarian follicular cyst that either formed a follicular cyst (Cyst), ovulated (Ov), or experienced normal growth and regression (NGR) in an environment with high (>1.0 ng/ml), intermediate (Int; 0.1–ng/ml), or low (<0.1 ng/ml) progesterone. This figure contains the same data as Figure 2, but the data are divided here by fate of follicle, not by progesterone classification. Follicle fate and progesterone classification were not independent (P < 0.01). Bars with different letters within follicle fate (Cyst, Ov, and NGR) are significantly different (P < 0.01)



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  		FIG. 6. Diameters of 2 newly formed ovulatory follicles ({circ}), of originally detected cystic follicles ({diamondsuit}, {blacktriangleup}), and circulating concentrations of progesterone ({square}) in a representative cow with low progesterone (<0.1 ng/ml for at least 1 day) during ovulatory follicle formation. The last day on which the newly formed ovulatory follicles were detected is designated by an asterisk. Days in which corpora lutea were detected are indicated by the two bold bars

Ovulation occurred at an average of 19.3 days (range, 6–46 days) after initial cyst confirmation. Because the precise time of initial cyst formation could not be determined, the initial cyst effectively suppressed ovulation for at least 19.3 days. Ovulation of a single follicle occurred in a majority of the cows (8 of 13), whereas some cows (5 of 13) ovulated multiple follicles. Double ovulations occurred in four of these cows, and one cow ovulated three follicles.

The phenomenon of cyst turnover was evident in this experiment. Overall, 51% (30 of 59) of traceable follicles formed ovarian follicular cysts. These 30 cysts were observed in 19 cows. In 75% of the cases of cyst formation, a single cyst formed; in the remaining 25%, two cysts developed within 3 days of each other. In cases of multiple cyst formation, cysts apparently formed from the same cohort of follicles. Cysts formed in all three progesterone categories (Fig. 5). Half of these cysts (15 of 30, observed in eight cows) formed in the presence of intermediate concentrations of progesterone (see representative animals in Figs. 3 and 4). Another large proportion of the cysts (13 of 30 [43%], observed in nine cows) developed in the presence of low concentrations of progesterone (see representative animal in Fig. 7). Only two cysts (7%, observed in two cows) developed in the presence of high circulating levels of progesterone.



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  		FIG. 7. Diameters of newly formed follicular cysts ({circ}, {triangleup}), of originally detected cystic follicle ({diamondsuit}), and circulating concentrations of progesterone ({square}) in a representative cow with low progesterone (<0.1 ng/ml) during cyst formation. The first day on which the newly formed cystic follicles reached the cystic diameter (≥17 mm) is indicated ({uparrow})

Only 10 of the 59 traceable follicles were classified as undergoing normal follicle growth and regression (observed in seven cows). Normal follicle growth and regression occurred in all three progesterone categories (Fig. 5) at a similar frequency.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Experiment 1 clearly demonstrated that the majority of ovarian follicular cysts (66%) were associated with an intermediate concentration of progesterone at the time of their detection. Only 28% of ovarian follicular cysts had low concentrations of progesterone. Thus, an intriguing association between an intermediate concentration of progesterone and the cystic condition was established. Experiment 2 suggests that this intermediate concentration of progesterone may predispose subsequent follicles to form cysts. Whether cysts initially formed because of the intermediate level of progesterone, or whether the intermediate level of progesterone is the result of the presence of the cyst, could not be determined in this experiment. The physiological significance of high plasma concentrations of progesterone in cows with follicular cysts could not be evaluated in our studies because of the rarity of occurrence.

The mechanism by which progesterone may contribute to cyst formation has not been determined. Subluteal levels of progesterone administered during the follicular phase can disrupt cyclic ovarian events. When circulating concentrations of progesterone are maintained at subluteal levels, the LH surge and subsequent ovulation can be prevented [15, 16]. These levels of progesterone were not associated with continuous follicular waves but, instead, prolonged the life span of the dominant follicle. This persistent follicle reached a greater maximum diameter (17 vs. 14 mm) and had a longer dominance period (11 vs. 5 days) than the ovulatory follicle of untreated controls. In nonlactating heifers, Duchens et al. [29, 30] reported that progesterone maintained at just 0.3 ng/ml during the follicular phase would delay ovulation and maintain the size of dominant follicles.

Formation of persistent follicles is associated with high LH pulse frequency. Subluteal levels of progesterone (1–2 ng/ml), maintained with progesterone-releasing intravaginal devices, do not inhibit LH pulsatility [19, 31], allowing the LH pulse frequency to reach a level comparable to that observed during the follicular phase [32]. Small doses of progesterone that result in subluteal concentrations of progesterone are capable of blocking the estradiol-induced preovulatory LH surge but do not slow the frequency of LH pulses [33]. This pattern of LH secretion may be an important contributor to the development of persistent follicles [34]. Persistent ovarian follicles have greater populations of LH receptors in granulosa and theca cells than the same cell types of dominant follicles [35]. Persistent follicles also contain more granulosa cells and have a larger thecal mass than dominant follicles contain [36]. This higher LH pulse frequency may promote follicular androgen production, leading to increased synthesis of estradiol [37].

Ovarian follicular cysts are similar in many ways to persistent anovulatory follicles induced by progesterone. First, both aberrant structures form because of a disruption in the follicular phase. Despite the fact that estradiol is secreted at a level that can induce an LH surge, estradiol does not induce an LH surge in cows with follicular cysts [10] or in cows with persistent follicles [15]. Second, both persistent follicles and ovarian follicular cysts are associated with high LH pulse frequency. Suppressing LH pulse frequency by administration of exogenous progesterone leads to regression of both persistent follicles maintained with progesterone and ovarian follicular cysts. Lastly, both follicular cysts and persistent follicles have been regressed by treatment with either a single injection of progesterone [38] or by several days of exposure to progesterone-releasing devices [15, 22].

The source of the intermediate level of progesterone found in cows with follicular cysts in these experiments is not known. Many investigators have examined intrafollicular fluid concentrations of progesterone in follicular cysts. Some cystic follicles contain high concentrations of progesterone in the follicular fluid [5, 18, 19]. Borromeo et al. [18] reported that follicular fluid of follicular cysts could be subdivided into an estradiol- or progesterone-dominant class. The reason why some follicular cysts have a relatively high concentration of intrafollicular progesterone and the extent to which progesterone is secreted are not known.

Ovaries with follicular cysts may be responsible for maintaining the cystic condition. Zaied et al. [13] reported that an estradiol injection was unable to induce a surge-like release of LH in cows with follicular cysts. DeSilva and Reeves [14] removed cystic ovaries and then injected estradiol 6 wk postovariectomy. This injection of estradiol induced a surge of LH. Whether the substance responsible for blocking the estradiol-induced LH surge is an ovarian factor, possibly progesterone, is presently unknown.

To our knowledge, this is the first comprehensive examination of follicular development in the presence of naturally occurring follicular cysts. Results from experiment 2 demonstrate the dynamic nature of the cystic condition. Only follicles that obtained a diameter of 10 mm of greater for 5 or 6 days were examined. Therefore, the follicles in the present study were most likely dominant follicles of a follicular wave. Only 17% (10 of 59) of these follicles experienced normal growth and regression. Our failure to detect more follicles in this group may result from the relatively infrequent ultrasound imaging schedule (three times per week) employed in this experiment. More than half of the follicles that were monitored in this experiment formed new cysts. This phenomenon is generally referred to as cyst turnover. Cook et al. [17] reported that 57% of all cystic follicles are replaced because of turnover. In experiment 2, 32% (19 of 59) of the traceable follicles ovulated. This frequency of ovulation is similar to that reported by Cook et al. but is somewhat less than that reported by Hamilton et al. [10]. Both Cook et al. [17] and Hamilton et al. [10] followed follicle dynamics in a mixed population of cows with both steroid-induced and spontaneously occurring cysts. The reason why cysts are frequently replaced by new cysts is unknown. One possibility is that the physiological condition that led to the formation of the original cyst is still present. Alternatively, the presence of a cyst may predispose new follicles to form cysts.

Not all cases of cyst formation can be attributed to the presence of intermediate progesterone concentrations. Forty-three percent of cysts formed in the presence of low progesterone. Thus, other mechanisms for cyst formation must exist. Recently, Gümen et al. [24, 39] have shown that premature induction of a preovulatory surge of LH, before development of an ovulatable follicle, resulted in persistent hypothalamic refractoriness to estradiol. Neither exogenous nor endogenous follicular estradiol were able to elicit an LH surge. Follicles that reached ovulatory size in this environment failed to ovulate and grew to an abnormally large size. This refractoriness to estradiol was overcome after cows were administered progesterone. Progesterone administration appeared to "reset" the hypothalamic surge center. Clearly, cyst-like structures can develop through multiple mechanisms.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Results from experiment 1 revealed that a majority of cows with follicular cysts had an intermediate concentration of progesterone at cyst diagnosis. In experiment 2, many of dominant follicles that emerged in the presence of a follicular cyst developed into a follicular cyst. Most follicles that developed in the presence of an intermediate concentration of progesterone formed new cysts. Ovulation typically occurred when the progesterone concentration fell to less than this intermediate level. Therefore, intermediate levels of progesterone commonly associated with cysts may predispose subsequent follicles to form cysts and contribute to the phenomenon of cyst turnover.


   ACKNOWLEDGMENTS
 
The authors would like to thank F. Button and the University of Kentucky farm crew for assistance in the care of the cows on these experiments along with A. Nugent and D. Yelton for assistance in data collection.


   FOOTNOTES
 
1 Supported by the U.S. Department of Agriculture (00-35203-9174), Kentucky Artificial Breeders Association, and the Kentucky Agriculture Experiment Station, and published with the approval of the director (publication number 02-07-153). Back

2 Correspondence: W.J. Silvia, Animal Sciences Department, 409 W.P. Garrigus Building, University of Kentucky, Lexington, KY 40506-0033. FAX: 859 257 7537; wsilvia{at}uky.edu Back

Received: 13 October 2002.

First decision: 5 November 2002.

Accepted: 26 February 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Garverick HA. Ovarian follicular cysts in dairy cows. J Dairy Sci 1997 80:995-1004[Abstract]
  2. Lee LA, Ferguson JD, Galligan DJ. The use of survival analysis to quantitate days open: advantages and implications. Acta Vet Scand Suppl 1988 84:433-435[Medline]
  3. Borsberry S, Dobson H. Periparturient diseases and their effect on reproductive performance in five dairy herds. Vet Rec 1989 124:217-219[Abstract]
  4. Eyestone WH, Ax RL. A review of ovarian follicular cysts in cows, with comparisons to the condition in women, rats, and rabbits. Theriogenology 1984 22:109-125
  5. Boryczko Z, Bostedt H, Hoffmann B. Comparison of hormonal and chemical composition of the fluid from bovine ovarian follicles and cysts. Reprod Domest Anim 1995 30:36-38
  6. Dobson H, Rankin JE, Ward WR. Bovine cystic ovarian disease: plasma hormone concentrations and treatment. Vet Rec 1977 101:459-461[Abstract]
  7. Farin PW, Youngquist RS, Parfet JR, Garverick HA. Diagnosis of luteal and follicular ovarian cysts in dairy cows by sector scan ultrasonography. Theriogenology 1990 34:633-642
  8. Farin PW, Youngquist RS, Parfet JR, Garverick HA. Diagnosis of luteal and follicular ovarian cysts by palpation per rectum and linear-array ultrasonography in dairy cows. J Am Vet Med Assoc 1992 200:1085-1089[Medline]
  9. Jeffcoate IA, Ayliffe TR. An ultrasonographic study of bovine cystic ovarian disease and its treatment. Vet Rec 1995 136:406-410[Abstract]
  10. Hamilton SA, Garverick HA, Keisler DH, Xu ZZ, Loos K, Youngquist RS, Salfen BE. Characterization of ovarian follicular cysts and associated endocrine profiles in dairy cows. Biol Reprod 1995 53:890-898[Abstract]
  11. Kittok RJ, Britt JH, Convey EM. Endocrine response after GnRH in luteal phase cows and cows with ovarian follicular cysts. J Anim Sci 1973 37:985-989
  12. Cantley TC, Garverick HA, Bierschwal CJ, Martin CE, Youngquist RS. Hormonal response of dairy cows with ovarian follicular cysts to GnRH. J Anim Sci 1975 41:1666-1673
  13. Zaied AA, Garverick HA, Kesler DJ, Bierschwal CJ, Elmore RG, Youngquist RS. Luteinizing hormone response to estradiol benzoate in cows postpartum and cows with ovarian cysts. Theriogenology 1981 16:349-358
  14. DeSilva MJ, Reeves JJ. Hypothalamic pituitary function of chronically cystic and regularly cycling dairy cows. Biol Reprod 1988 38:264-269[Abstract]
  15. Stock AE, Fortune JE. Ovarian follicular dominance in cattle: relationship between prolonged growth of ovulatory follicle and endocrine parameters. Endocrinology 1993 132:1108-1114[Abstract]
  16. Sirois J, Fortune JE. Lengthening the bovine estrous cycle with low levels of exogenous progesterone: a model for studying ovarian follicular dynamics. Endocrinology 1990 127:916-925[Abstract]
  17. Cook DL, Smith CA, Parfet JR, Youngquist RS, Brown EM, Garverick HA. Fate and turnover rate of ovarian follicular cysts in dairy cattle. J Reprod Fertil 1990 90:37-46[Abstract]
  18. Borromeo V, Bramani S, Berrini A, Sironi G, Finazzi M, Cremonesi F, Seccgi C. Growth hormone but not prolactin concentrations in the fluid of bovine ovarian cysts are related to the cystic stage of luteinization. Theriogenology 1996 46:481-489
  19. Ireland JJ, Roche JF. Effect of progesterone on basal LH and episodic LH and FSH secretion in heifers. J Reprod Fertil 1982 64:295-302[Abstract]
  20. Carroll DJ, Pierson RA, Hauser ER, Grummer RR, Combs DK. Variability of ovarian structures and plasma progesterone profiles in dairy cows with ovarian cysts. Theriogenology 1990 34:349-370
  21. Yoshioka K, Suzuki C, Shozo A, Iwamura S, Hirose H. Gonadotropin-releasing hormone in the third ventricular cerebrospinal fluid of the heifer during the estrous cycle. Biol Reprod 2001 64:563-570[Abstract/Free Full Text]
  22. Calder MD, Salfen BE, Bao B, Youngquist RS, Garverick HA. Administration of progesterone to cows with ovarian follicular cysts results in a reduction in mean LH and LH pulse frequency and initiates ovulatory follicular growth. J Anim Sci 1999 77:3037-3042[Abstract/Free Full Text]
  23. Ginther OJ, Knopf L, Kastelic JP. Temporal association among ovarian events in cattle during oestrous cycles with two and three follicular waves. J Reprod Fertil 1989 87:223-230[Abstract]
  24. Gümen A, Sartori R, Costa FMJ, Wiltbank MC. A GnRH/LH surge without subsequent progesterone exposure can induce development of follicular cysts. J Dairy Sci 2002 85:43-50[Abstract]
  25. Snedecor GW, Cochran W. Statistical Methods, 7th ed. Ames, IA: The Iowa State University Press; 1980:288–292
  26. Chenault JR, Thatcher WW, Kalra PS, Abrams RM, Wilcox CJ. Transitory changes in plasma progestins, estradiol, and luteinizing hormone approaching ovulation in the bovine. J Dairy Sci 1975 58:709-717
  27. SAS User's Guide: Statistics, 1999, Version 8. Cary, NC: SAS Institute
  28. Patterson DJ, Hall JB, Bradley NW, Schillo KK, Woods BL, Kearnan JM. Improved synchrony, conception rate, and fecundity in postpartum suckled beef cows fed melengestrol acetate prior to prostaglandin F2 alpha. J Anim Sci 1995 73:954-959[Abstract]
  29. Duchens M, Forsberg M, Edqvist LE, Gustafsson H, Rodriguez-Martinez H. Effect of induced suprabasal progesterone levels around estrus on plasma concentrations of progesterone, estradiol-17ß, and LH in heifers. Theriogenology 1994 42:1159-1169
  30. Duchens M, Maciel M, Gustafsson H, Forsberg M, Rodriguez-Martinez H, Edqvist LE. Influence of perioestrous suprabasal progesterone levels on cycle length, oestrous behaviour and ovulation in heifers. Anim Reprod Sci 1995 37:95-108[CrossRef]
  31. Roberson MS, Wolfe MW, Stumpf TT, Kittok RJ, Kinder JE. Luteinizing hormone secretion and corpus luteum function in cows receiving two levels of progesterone. Biol Reprod 1989 41:997-1003[Abstract]
  32. Imakawa K, Day ML, Zalesky DD, Garcia-Winder M, Kittok RJ, Kinder JE. Regulation of pulsatile LH secretion by ovarian steroids in the heifer. J Anim Sci 1986 63:162-168
  33. Kinder JE, Kojima FN, Bergfeld EMG, Wehrman ME, Fike KE. Progestin and Estrogen regulation of pulsatile LH release and development of persistent ovarian follicles in cattle. J Anim Sci 1996 74:1424-1440[Abstract]
  34. Cupp AS, Garcia-Winder M, Zamudio A, Mariscal V, Wehrman M, Kojima N, Peters K, Bergfeld E, Hernandez P, Sanchez T, Kittok R, Kinder J. Two concentrations of progesterone in circulation have a differential effect on pattern of ovarian follicular development in the cow. Biol Reprod 1992 46:suppl 1106 (abstract)
  35. Cupp A, Garcia-Winder M, Zamudio A, Mariscal V, Wehrmanm M, Kojima N, Peters K, Bergfeld E, Hernandez P, Sanchez T, Kittok R, Kinder J. Concentrations of progesterone in circulation have a differential effect on biochemical characteristics of dominant follicles in cows. J Anim Sci 1993 71:suppl 1211 (abstract)
  36. Bigelow KL, Fortune JE. Characteristics of prolonged dominant versus control follicles: follicle cell numbers, steroidogenic capabilities, and messenger ribonucleic acid for steroidogenic enzymes. Biol Reprod 1998 58:1241-1249[Abstract/Free Full Text]
  37. Fortune JE. Bovine theca and granulosa cells interact to promote androgen production. Biol Reprod 1986 35:292-299[Abstract]
  38. Anderson LH, Day ML. Acute progesterone administration regresses persistent dominant follicles and improves fertility in cattle in which estrus was synchronized with melengestrol acetate. J Anim Sci 1994 72:2955-2961[Abstract]
  39. Gümen A, Wiltbank MC. An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle. Biol Reprod 2002 66:1689-1695[Abstract/Free Full Text]



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