| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Minireview |
a Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
estradiol, follicle, follicular development, granulosa cells, growth factors, ovary, theca cells
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
) during its tenure of dominance. The first wave of the cycle is particularly useful for experimental purposes, because it begins at a predictable time, in the absence of the previous dominant follicle (which has just ovulated). This manuscript will review some of the current literature on follicular selection. The most obvious sign that a follicle has been selected as dominant is a significant difference in size, compared to the largest subordinate follicle. This difference in follicular diameter, sometimes referred to as "follicle deviation" [2] is a consequence of an increased growth rate of the dominant follicle relative to the subordinate follicles. It is likely that selection of the dominant follicle is a progressive process and that the initial stages of selection occur before there is a perceptible difference in size. Hence it is difficult, on the basis of current knowledge, to define when selection occurs. For the purposes of this review, selection will mean morphological selection, the detection of an evident difference in diameter between the two largest follicles of a wave. One approach to the question of the mechanisms of follicular selection is to compare the characteristics of follicles of a cohort before selection with the characteristics of selected, clearly dominant follicles. Another approach is to compare the characteristics of dominant and subordinate follicles, from the same animals, at specific times during a follicular wave. Results of studies in which these approaches were used will be reviewed below. These strategies of comparison, while not optimal, have helped to pinpoint key differences between dominant and subordinate follicles. Additionally, it is now possible to sample follicular fluid in vivo from follicles of a cohort to identify characteristics that precede, and hence are predictive of, morphological selection.
|
RECRUITMENT OF FOLLICULAR WAVES |
|---|
|
TOPABSTRACTINTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
|
SELECTION OF FOLLICLES FOR DOMINANCE |
|---|
|
TOPABSTRACTINTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
A defining characteristic of the dominant follicle appears to be its greater capacity for estradiol production. As shown in Table 1, concentrations of estradiol in follicular fluid were much higher in dominant follicles isolated on Day 5 of the estrous cycle than in recruited follicles on Day 3, whereas subordinate follicles on Day 5 had concentrations similar to recruited follicles on Day 3 [3, 6]. More recently, dominant and subordinate follicles were compared at specific times, relative to the appearance of a morphologically dominant follicle. As soon as the dominant follicle was detected as just slightly larger than the largest subordinate follicle, it had higher concentrations of estradiol in the follicular fluid [7–9], and its granulosa cells secreted more estradiol in vitro [8]. It appears that the dominant follicle is the source of the higher circulating concentrations of estradiol and androgen detected in the peripheral (vena cava) circulation during the first follicular wave of the cycle, since concentrations of estradiol, androstenedione, and testosterone increase in the utero-ovarian vein draining the ovary bearing the dominant follicle but not in the contralateral utero-ovarian vein [10]. Secretion of estradiol, and perhaps androgen, by the dominant follicle is associated with termination of the rise in FSH and with maintenance of FSH at basal levels, respectively [10–12]. Although there is evidence that circulating inhibin also regulates FSH during the early luteal phase [13], its role in controlling the interval between successive increases in FSH is not clear, since assays for dimeric inhibin have only recently become available for ruminants [14].
|
What is different about the future dominant follicle that allows it to respond more robustly or earlier than the subordinates to the small rise in FSH that initiates the wave of follicular development? The dominant follicle may be uniquely positioned, by virtue of slightly larger size or a better blood supply, to respond to the rise in FSH and increase its secretion of estradiol. Careful ultrasonographic studies have shown that, early in a follicular wave, the future dominant follicle is, on average, slightly larger than others in the cohort [15, 16]. However, the difference in size is small and not always predictive of future dominance, which suggests that intrafollicular mechanisms within the dominant follicle allow it to amplify the effects of FSH and thus, respond much more robustly than the subordinate follicles to the rise in circulating FSH. Characteristics of the dominant follicle that may subserve its greater capacity for estradiol production have been examined by comparing recruited follicles, before morphological selection, with dominant follicles obtained after selection or by comparing dominant and subordinate follicles at specific times shortly after morphological selection. Those studies are reviewed in the sections that follow.
Characteristics of Recruited Versus Selected Follicles
A number of characteristics of recruited and selected follicles have been examined by reproductive biologists at the University of Missouri and presented in a series of papers (reviewed in [17]). Follicles were obtained every 2 days during the first 10 days of the bovine estrous cycle and mRNAs for steroidogenic enzymes and gonadotropin receptors were examined by in situ hybridization. These studies allowed comparisons of recruited follicles (Days 0–2 of the wave) and selected follicles (Days 4–10), but dominant and subordinate follicles were not compared. As expected, selected follicles had significantly higher concentrations of estradiol in the follicular fluid than recruited or regressing follicles (Table 2). In granulosa cells, levels of mRNA for P450 aromatase (aromatase), which converts androgens to estradiol, increased between 0 and 2 days after initiation of the wave, whereas in theca cells mRNA for P450 17-hydroxylase (17-OH), which converts progestins to androgens, increased between Days 2 and 4, concomitant with higher estradiol in selected follicles on Day 4 than in recruited follicles on Days 0–2 (Tables 2 and 3 [18]). Changes were also observed in mRNAs for enzymes involved in progestin biosynthesis. Levels of mRNA for P450 side chain cleavage enzyme (P450scc) were higher in granulosa cells of selected (dominant) follicles obtained on Day 4 of the wave than in recruited follicles obtained before selection (Table 3 [18]). Expression of mRNA for LH receptor (LHr) was higher in theca and granulosa cells of selected follicles on Day 4 of the wave than in recruited follicles on Days 0–2 (Table 4 [19]).
|
|
|
In a second series of experiments, the Missouri group isolated follicles every 12 h during the first 4 days of the first follicular wave to provide more information about changes specifically associated with selection of the dominant follicle. Expression of mRNA for FSH receptor (FSHr) in granulosa cells and for LHr in theca cells was greater in dominant versus recruited follicles by Day 2 of the wave [20]. Messenger RNA for LHr was not detected in granulosa cells during the first 24 h of the wave, but its expression was detected in one follicle per heifer around the time of selection (36–60 h of the wave) [20]. Additionally, mRNA for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) had increased in theca cells of recruited follicles by Day 1 of the wave, compared with Day 0.5 and later in granulosa cells of selected versus recruited follicles by Days 1.5–2 [21]. Messenger RNA for steroidogenic acute regulatory protein (StAR) was not detected in granulosa cells but was elevated in theca cells of selected versus recruited follicles by Day 2 of the wave [22].
Taken together, these interesting and comprehensive studies show that, early in a wave of follicular development, mRNA for aromatase increases in recruited follicles and that after selection, dominant follicles have higher levels of mRNAs for gonadotropin receptors and enzymes involved in androgen and progestin synthesis (17-OH, P450scc, 3ß-HSD, and StAR) than recruited follicles. It has been hypothesized that the dominant follicle is selected because it acquires LHr on its granulosa cells and that this allows the cells to synthesize estradiol in response to LH, as well as FSH (reviewed in [2, 3]). The findings of the Missouri group lend support to the idea that acquisition of LHr on granulosa cells may be a critical component of selection for dominance.
Characteristics of Dominant Versus Subordinate Follicles
Our laboratory took a different approach and compared characteristics of dominant versus subordinate follicles around the time of morphological selection of the dominant follicle. The dominant and two largest subordinate follicles were obtained on Days 2 and 3 of the first follicular wave of the cycle and levels of mRNA for steroidogenic enzymes and gonadotropin receptors were examined by in situ hybridization. We were particularly interested in comparing mRNAs for gonadotropin receptors in dominant versus subordinate follicles, to test the hypothesis that acquisition of LHr on granulosa cells is associated with selection of the dominant follicle. Contrary to this hypothesis, mRNA for LHr was not detected in granulosa cells of either dominant or subordinate follicles, although it was readily detectable in theca cells of the same follicles (Table 5 [8]). In these experiments, the only difference detected between dominant and subordinate follicles on Day 2 of the follicular wave was that dominant follicles had much higher concentrations of estradiol in their follicular fluid and their granulosa cells secreted considerably more estradiol in culture. By Day 3 of the wave, additional differences were observed; compared to the dominant follicle, subordinate follicles had lower levels of mRNA for LHr and 17-OH in theca cells and for FSHr and aromatase in granulosa cells (Table 5).
|
Therefore, when dominant and subordinate follicles were compared directly, very close to the time of selection (i.e., Day 2 of a follicular wave), the only difference noted, besides the small difference in follicular diameter, was in follicular capacity to produce estradiol. These data suggest that acquisition of LHr by granulosa cells is not a key component of follicular selection, since it appears to occur after, rather than before, selection has occurred. Similarly, Bodensteiner et al. [7] reported that increased estradiol in follicular fluid preceded an increase in gonadotropin receptors detected by radioreceptor assay. It is not clear why granulosa cells develop LHr. It was hypothesized that this allows the granulosa cells to increase aromatase in response to both FSH and LH or allows them to shift from FSH- to LH-dependence, and that this increases, or at least maintains, their capacity to produce more estradiol than subordinate follicles. However, there are no published reports of LH stimulation of estradiol production by bovine granulosa cells. We have cultured bovine granulosa cells, obtained from preovulatory follicles before the LH surge, with a very wide range of doses of LH (0.008–256 ng/ml) and have observed no stimulatory effects on aromatization of androgen to estradiol, although high doses of LH that simulate the LH surge inhibit estradiol production ([23]; unpublished data). In contrast, progesterone secretion by granulosa cells from bovine dominant follicles can be readily stimulated by LH [23]. On the other hand, LH does stimulate aromatization by granulosa cells from human and rat preovulatory follicles [24, 25]. However, in these species the corpora lutea synthesize estradiol, which makes it difficult to determine, without extensive dose-response studies, whether the estradiol production simply is due to luteinization of the granulosa cells in vitro in response to high doses of LH. Another possibility is that LHr develop on granulosa cells of dominant follicles to prepare them for further differentiation in response to the LH surge, rather than to augment or maintain their estradiol-secreting capacity. Further study is needed to determine the purpose of LHr on granulosa cells and to determine whether there are important species differences.
At the same time, experimental evidence derived from studies with primates [26] and sheep [27] supports the hypothesis that LH is critical for the survival of the dominant follicle after the decline in circulating FSH. How LH maintains follicular viability and estradiol-secreting capacity is not as clear. There are at least two potential mechanisms, which need not be mutually exclusive. The theca cells may be the primary target for LH during this period of follicular development, and maintenance of thecal androgen secretion may be the limiting factor for estradiol production once dominance is established. There is evidence that production of progesterone by granulosa cells enhances thecal cell production of androgen by increasing the amount of available precursor [28], so LH could increase progestin production by granulosa cells of the dominant follicle and thus indirectly increase estradiol production.
Potential Role of the Insulin-Like Growth Factor System in Selection of the Dominant Follicle
The findings discussed above suggest that some change(s) in the dominant follicle, other than acquisition of LHr by granulosa cells, drives its greater capacity for estradiol secretion and allows it to pull ahead of the subordinate follicles. Once this happens, the dominant follicle would be able to exert dominance via negative feedback on circulating levels of FSH, but it must also develop mechanisms that enable its continued survival in the face of lower FSH. There is increasing evidence that the insulin-like growth factor (IGF) system may play a critical part in selection of the dominant follicle. IGFs are believed to play an important role in follicular growth by stimulating granulosa cell proliferation and synergizing with gonadotropins to promote differentiation of follicle cells [29, 30]. Targeted deletion of the IGF-I gene in mice leads to the development of an ovarian phenotype characterized by failure of follicles to ovulate, showing that IGF is absolutely required for normal follicular development [31]. The IGF system has a number of components, including two ligands (IGF-I and IGF-II), two receptors (type 1 and type 2), and six different IGF-binding proteins (IGFBP-1, -2, -3, -4, -5, and -6) (reviewed in [29, 30, 32, 33]). The actions of IGFs are exerted mainly through the type 1 receptors, but binding of IGFs to their receptors can be modulated by the IGFBPs. Although both stimulatory and inhibitory effects of the IGFBPs on the actions of IGFs have been described in different target tissues [32, 34], there seems to be consensus that IGFBPs are inhibitory to gonadotropin-induced follicular growth and differentiation [29, 30, 33]. Thus, changes in intrafollicular IGFBP levels may lead to changes in IGF bioavailability and hence, to up- or downregulation of gonadotropin actions on follicle cells.
Most of the components of the IGF system have been identified in the bovine ovary. Messenger RNAs for IGF-I and -II were localized to granulosa and theca cells, respectively, of small antral, subordinate, and dominant follicles by Yuan et al. [35], whereas Armstrong et al. [36] did not detect mRNA for IGF-I in theca or granulosa cells. IGF-I binds to both granulosa and theca cells [37, 38] and stimulates proliferation in vitro of granulosa cells from small antral follicles [37, 39] and estradiol production in vitro by granulosa cells from large antral follicles [37]. Although the expression of mRNAs for IGFs increases in dominant follicles, intrafollicular concentrations of IGFs are not correlated with follicular fluid estradiol concentrations [38, 40–43], suggesting that the actual bioavailability of IGFs at the follicular level is more likely determined by levels of the IGFBPs rather than by IGF gene expression in ovarian tissues. Bovine follicular fluid contains IGFBP-2, -3, -4, and -5 [38, 43], and IGFBP-2 and IGFBP-4 mRNAs were localized to granulosa and theca cells, respectively [35, 44]. Although IGFBP-3 is the predominant species in the blood and in follicular fluid [45], in most species examined, IGFBP-3 is expressed barely or not at all in ovarian tissues. Intrafollicular fluctuations in IGFBP-3 levels are thus, likely a reflection of changes in vascular permeability accompanying follicular development. Of more interest are the intrafollicular levels of low molecular weight (MW; <40 kDa) IGFBPs (IGFBP-2, -4, and -5), as they appear to be developmentally and hormonally regulated. Indeed, follicular fluid concentrations of low MW IGFBPs were higher in subordinate/atretic follicles compared to estrogen-active/dominant follicles [38, 40, 43, 46].
The concentrations of low molecular weight IGFBPs in bovine follicles may be controlled by the level of gene expression in ovarian tissues, the degradation rate by local proteolytic activity, or a combination of both factors. IGFBP-2 and -4 appear to be the major binding proteins produced in ovine and bovine follicles [35, 44, 47]. In bovine follicles, IGFBP-2 mRNA expression was localized by in situ hybridization to granulosa cells of small- and medium-sized antral follicles, but was absent in healthy, large (>8-mm) or dominant follicles. Further evidence in support of hormonal regulation of IGFBP-2 at the level of mRNA expression was provided by the finding that FSH inhibited IGFBP-2 mRNA expression in cultured granulosa cells obtained from medium-sized, bovine follicles [44]. In the same study, IGFBP-4 mRNA was localized to theca tissue of healthy antral follicles, regardless of the size class, and was stimulated by LH in primary cultures of theca cells obtained from medium-sized follicles. These findings suggest that intrafollicular IGFBP-4 is regulated at the level of degradation and indeed, our laboratory has reported increased IGFBP-4 protease activity in follicular fluid of dominant versus subordinate bovine follicles [48]. Additionally, we have recently developed and validated a model for inducing the development of codominant follicles in cattle by injecting small doses of recombinant bovine FSH (rbFSH) during the expected time of dominant follicle selection [5]. Interestingly, size (as assessed by ultrasonography) and concentrations of estradiol and IGFBP-4 proteolytic activity in the follicular fluid were similar for the two codominant follicles of the rbFSH-treated animals (Table 6). Follicular diameter and IGFBP-4 proteolytic activity were also similar to the single dominant follicle of control heifers and greater than the largest subordinate follicle of controls.
|
It is worth emphasizing that all of the studies previously mentioned have evaluated the involvement of the IGF system in bovine follicular development in follicles obtained just after the time of morphological selection or in follicles whose stage of development was undetermined (slaughterhouse ovaries). To determine whether the differences observed are important components of the acquisition of dominance, studies addressing the role of the IGF system at the critical times of follicle selection are needed. In this regard, Mihm et al. [16] used this approach recently and reported that when follicular fluid was sampled in vivo on Day 1.5 of the first follicular wave (Day 3 of the cycle), the follicle with the lowest concentration of IGFBP-4 always became the dominant follicle (Table 7). In contrast, concentrations of the other low MW IGFBPs (IGFBP-2 and -5) were not predictive of future dominance, and IGFBP-4 concentration was more predictive than follicular fluid estradiol or follicular diameter at this early stage of the follicular wave. It is tempting to speculate that the lower concentrations of IGFBP-4 observed in the dominant follicle before morphological selection are the result of elevated levels of IGFBP-4 proteolysis in the future dominant follicle and that these differences, by increasing bioavailable IGF, mediate the greater capacity of the dominant follicle to produce estradiol. Further studies are needed to test this hypothesis, which is outlined in Figure 1.
|
|
|
DIFFERENTIATION OF DOMINANT FOLLICLES |
|---|
|
TOPABSTRACTINTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
-OH and increased androgen secretion, without a change in mRNA for aromatase [49]. Thus, it appears that dominant follicles can "coast" for at least several days after selection and still respond to the increased LH pulse frequency that accompanies luteal regression by an increase in estradiol during the ensuing follicular phase. |
SUMMARY AND CONCLUSIONS |
|---|
|
TOPABSTRACTINTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
|
FOOTNOTES |
|---|
1 Supported by grants from the National Institutes of Health (HD-38276) and the U.S. Department of Agriculture (93-37203-9022). 
2 Correspondence: J.E. Fortune, T6-012B VRT, Cornell University, Ithaca,
NY 14853. FAX: 607 253 3476; jf11{at}cornell.edu
3 Current address: Department of Animal Science and Production, University
College Dublin, Belfield, Dublin 4, Ireland.
4 Current address: Department of Physiology, University of Arizona, Tucson,
AZ 85724-5051.
Accepted: March 19, 2001.
Received: October 13, 2000.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONRECRUITMENT OF FOLLICULAR WAVESSELECTION OF FOLLICLES FOR...DIFFERENTIATION OF DOMINANT...SUMMARY AND CONCLUSIONSREFERENCES |
|---|
ßA dimer) during the oestrous cycle, after manipulation of ovarian activity and during pregnancy in ewes. J Reprod Fertil 1998; 113:159-166[Abstract]-hydroxylase, and cytochrome P450 aromatase in bovine follicles during the first follicular wave. Endocrinology 1995; 136:981-989[Abstract]
4,5 isomerase (3ß-HSD) during recruitment and selection of bovine ovarian follicles: identification of dominant follicles by expression of 3ß-HSD mRNA within the granulosa cell layer. Biol Reprod 1997; 56:1466-1473[Abstract]-hydroxylase, but not P450 aromatase. Endocrinology 1995; 136:5102-5110[Abstract]This article has been cited by other articles:
|
|
 |
|
  A. T. Grazul-Bilska, C. Navanukraw, M. L. Johnson, K. A. Vonnahme, S. P. Ford, L. P. Reynolds, and D. A. Redmer Vascularity and expression of angiogenic factors in bovine dominant follicles of the first follicular wave J Anim Sci, August 1, 2007; 85(8): 1914 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Llewellyn, R Fitzpatrick, D A Kenny, J J Murphy, R J Scaramuzzi, and D C Wathes Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows Reproduction, March 1, 2007; 133(3): 627 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Fayad, R. Lefebvre, J. Nimpf, D. W. Silversides, and J. G. Lussier Low-Density Lipoprotein Receptor-Related Protein 8 (LRP8) Is Upregulated in Granulosa Cells of Bovine Dominant Follicle: Molecular Characterization and Spatio-Temporal Expression Studies Biol Reprod, March 1, 2007; 76(3): 466 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Lucy The bovine dominant ovarian follicle J Anim Sci, March 1, 2007; 85(13_suppl): E89 - E99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sahmi, E. S Nicola, and C. A Price Hormonal regulation of cytochrome P450 aromatase mRNA stability in non-luteinizing bovine granulosa cells in vitro. J. Endocrinol., July 1, 2006; 190(1): 107 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Campbell, J. Dickey, B. Beckman, G. Young, A. Pierce, H. Fukada, and P. Swanson Previtellogenic Oocyte Growth in Salmon: Relationships among Body Growth, Plasma Insulin-Like Growth Factor-1, Estradiol-17beta, Follicle-Stimulating Hormone and Expression of Ovarian Genes for Insulin-Like Growth Factors, Steroidogenic-Acute Regulatory Protein and Receptors for Gonadotropins, Growth Hormone, and Somatolactin Biol Reprod, July 1, 2006; 75(1): 34 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cao, J. Buratini Jr, J. G Lussier, P. D Carriere, and C. A Price Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle Reproduction, January 1, 2006; 131(1): 125 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Buratini Jr, A B Teixeira, I B Costa, V F Glapinski, M G L Pinto, I C Giometti, C M Barros, M Cao, E S Nicola, and C A Price Expression of fibroblast growth factor-8 and regulation of cognate receptors, fibroblast growth factor receptor-3c and -4, in bovine antral follicles Reproduction, September 1, 2005; 130(3): 343 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ndiaye, T. Fayad, D. W. Silversides, J. Sirois, and J. G. Lussier Identification of Downregulated Messenger RNAs in Bovine Granulosa Cells of Dominant Follicles Following Stimulation with Human Chorionic Gonadotropin Biol Reprod, August 1, 2005; 73(2): 324 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J H Hampton, J F Bader, W R Lamberson, M F Smith, R S Youngquist, and H A Garverick Gonadotropin requirements for dominant follicle selection in GnRH agonist-treated cows Reproduction, June 1, 2004; 127(6): 695 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fayad, V. Levesque, J. Sirois, D. W. Silversides, and J. G. Lussier Gene Expression Profiling of Differentially Expressed Genes in Granulosa Cells of Bovine Dominant Follicles Using Suppression Subtractive Hybridization Biol Reprod, February 1, 2004; 70(2): 523 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Quirk, R. G. Cowan, R. M. Harman, C.-L. Hu, and D. A. Porter Ovarian follicular growth and atresia: The relationship between cell proliferation and survival J Anim Sci, January 1, 2004; 82(13_suppl): E40 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-G. Hayashi, T. J. Acosta, M. Tetsuka, B. Berisha, M. Matsui, D. Schams, M. Ohtani, and A. Miyamoto Involvement of Angiopoietin-Tie System in Bovine Follicular Development and Atresia: Messenger RNA Expression in Theca Interna and Effect on Steroid Secretion Biol Reprod, December 1, 2003; 69(6): 2078 - 2084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sisco, L. J. Hagemann, A. N. Shelling, and P. L. Pfeffer Isolation of Genes Differentially Expressed in Dominant and Subordinate Bovine Follicles Endocrinology, September 1, 2003; 144(9): 3904 - 3913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Rivera and J. E. Fortune Proteolysis of Insulin-Like Growth Factor Binding Proteins -4 and -5 in Bovine Follicular Fluid: Implications for Ovarian Follicular Selection and Dominance Endocrinology, July 1, 2003; 144(7): 2977 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bauersachs, H. Blum, S. Mallok, H. Wenigerkind, S. Rief, K. Prelle, and E. Wolf Regulation of Ipsilateral and Contralateral Bovine Oviduct Epithelial Cell Function in the Postovulation Period: A Transcriptomics Approach Biol Reprod, April 1, 2003; 68(4): 1170 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Rivera and J. E. Fortune Selection of the Dominant Follicle and Insulin-Like Growth Factor (IGF)-Binding Proteins: Evidence that Pregnancy-Associated Plasma Protein A Contributes to Proteolysis of IGF-Binding Protein 5 in Bovine Follicular Fluid Endocrinology, February 1, 2003; 144(2): 437 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O.J. Ginther, M.A. Beg |
