Relationship among the status of the human oocyte, the 17 beta-estradiol concentration in the antral fluid and the follicular size

We studied the relationship among the status of the human oocytes, the E2 concentration in the antral fluid and the follicular size in the different phases of the menstrual cycle, in order to determine the microenvironment of the follicles with healthy or degenerative oocytes in the human ovary. In the follicular phase of the menstrual cycle, follicles which contained a healthy but not degenerative oocyte had a significantly higher level of 17 beta-estradiol (E2). In the late follicular phase, the larger follicles (greater than or equal to 13 mm, in diameter) had only health oocytes. It seems that the follicle containing a degenerative oocyte does not develop physiologically until maturation of the preovulatory follicle. In the luteal phase, there were no relationships among the status of the oocyte, E2 concentration in the antral fluid and the follicular size. However, the E2 levels of the antral follicles with healthy oocytes in an ovary with corpus luteum were significantly lower than those in the contralateral ovary. The results suggest that the corpus luteum may exert an influence on the adjacent follicles.     

Evolution of the diameters of the largest healthy and atretic follicles during the human menstrual cycle

Analysis of ovaries from 31 women with normal ovarian function permitted study of the diameter of the largest healthy and atretic follicles during the menstrual cycle. The follicle destined to ovulate is selected during the early follicular phase (Days 1-5). Throughout the cycle the diameter of the largest healthy follicles, with the exception of the dominant follicle, did not exceed, on average, 6 mm during the follicular phase and 4 mm during the luteal phase. Consequently, excluding the dominant follicle during the second half of the follicular phase, the largest follicles present in the human ovary are atretic. From these data, it was concluded that a new ovulation could not occur very soon after a spontaneous or experimentally induced premature disappearance of the dominant follicle or the corpus luteum of the cycle.     

Local regulatory factors in regulation of ovarian function: role of prorenin-renin-angiotensin-system

During reproductive life in the female, there is a continuous flow of growth, maturation and demise of ovarian follicles, unless pregnancy occurs. Although ovarian function is primarily controlled by the hypothalamus-pituitary-axis, there is no doubt that a hormonal microenvironment specific for each individual follicle is established, that finally determines whether a follicle ovulates and becomes a corpus luteum or undergoes atresia. In this respect, autocrine and paracrine factors that act alone or modulate gonadotropins action are of paramount importance. In this article, we want to introduce the ovarian prorenin-renin-angiotensin-system (PRAS) and summarize what is actually known about its involvement in ovarian physiology and pathology.     

Effect of enucleation of the corpus luteum at different stages of the luteal phase of the human menstrual cycle on subsequent follicular development

To investigate the mechanism of suppression of follicular development during the luteal phase of the human menstrual cycle, the corpus luteum was enucleated surgically from 10 women at various times after ovulation. In the 24 h after CL enucleation there was an immediate and rapid fall in the concentration of oestradiol and progesterone and a temporary decline in the concentration of FSH and LH. Within 3 days, however, all 10 women showed evidence of renewed follicular activity as indicated by a progressive rise in the concentration of oestradiol. This rise was preceded by a rise in the concentration of FSH and LH, and ovulation, as indicated by a mid-cycle surge in LH and rise in the concentration of plasma progesterone, occurred 16-19 days after enucleation. There was no significant difference in the time to ovulation following enucleation at different times of the luteal phase. The post-operative follicular phase, measured from the time of enucleation, was 3 days longer than that observed pre-operatively from the first day of menstrual bleeding. In the follicular phase of post-operative cycles the concentration of FSH was higher and that of oestradiol lower than the corresponding values before surgery. These results indicate that the absence of healthy antral follicles in the luteal phase of the cycle is due to the inhibitory effects of the corpus luteum. The fact that, after CL enucleation, emergence of the dominant follicle was always preceded by a rise in the concentration of FSH and LH suggests that suppression of gonadotrophins by ovarian steroids secreted by the corpus luteum is responsible for the inhibition of follicular development during the luteal phase of the cycle.     

Intraovarian relationships among dominant and subordinate follicles and the corpus luteum in heifers

Previous studies demonstrated that waves of follicular activity develop approximately every 9 d in cattle during the estrous cycle and early pregnancy. A dominant follicle develops from each wave and the remaining follicles (subordinates) begin to regress after a few days. In this study, intraovarian luteal and follicular interrelationships were examined during the follicular waves of the estrous cycle and pregnancy using data obtained by ultrasonography. During the estrous cycle, no intraovarian relationships were found between the ovary containing the corpus luteum and the ovary containing the dominant follicle (n = 165), or between the location of the corpus luteum and the characteristics of the dominant follicle. During pregnancy, however, the frequency distribution for the number of follicular waves with the dominant follicle and corpus luteum on the same or opposite ovaries differed (P<0.05) among Waves 1 to 10. The two structures (dominant follicle and corpus luteum) were more often in opposite ovaries during Waves 3 to 10 (combined frequency, 75%) than during Waves 1 and 2. During pregnancy, dominant follicles of consecutive waves differed (P<0.05) among Waves 1 to 8 in the frequency with which they appeared in the same versus the opposite ovary. The difference seemed primarily due to an increased frequency of consecutive follicles on the same ovary for Waves 4 to 8 (combined frequency, 80%). During both the estrous cycle and pregnancy, there was no significant intraovarian effect of the dominant follicle on the day of detection of the next dominant follicle, on the growth rate of the largest subordinate follicle, or on the length of the interval from wave origin to cessation of growth of the largest subordinate; these results indicate that previously postulated suppressive effects between follicles are exerted through systemic channels.     

Morphological changes of the ovary and hormonal changes through the ovarian cycle of the common marmoset (Callithrix jacchus)

Laparoscopic observations of morphological changes of the ovary during the ovarian cycle in conjunction with radioimmunoassay of serum progesterone and estradiol-17β was investigated as a method of monitoring the ovarian cycle in the common marmoset. In the common marmoset, plural follicles first appeared in each ovary five days prior to ovulation. At three to four days prior to ovulation one or two follicles developed into translucent blisters on the surface of the ovary. As the follicles filled with follicular fluid, they became larger and clearer until one to two days prior to ovulation, at which time they formed well defined, transparent bubbles protruding from the surface of the ovary. After ovulation, the ovulation point could be detected at the center of the follicle, sometimes surrounded by a corpus of engorged blood vessels. Ovulations of the plural follicles were not simultaneous, and due to the time lag ovulations took at least 12 to 20 hrs in four out of seven animals examined. After two to five days of ovulation the corpus hemorragicum, a bright red protrusion made of tissue and blood disrupted by ovulation, was found. Subsequently, the color of the formatted corpus luteum changed from dark-red to yellow then to yellow white. While the corpus luteum remained reddish in color serum progesterone was maintained at as high levels as in the luteal phase. There was no mature follicle or corpus luteum in subordinate female ovaries.     

Short- and long-term effects of unilateral ovariectomy in sheep: causative mechanisms

The mechanisms of ovulatory compensation following unilateral ovariectomy (ULO) are still not understood. In the present study, we investigated the short- and long-term effects of ULO in sheep using transrectal ovarian ultrasonography and hormone estimations made during the estrous cycle in which surgery was done, the estrous cycle 2 mo after surgery, and the 17-day period during the subsequent anestrus. The ULOs were done when a follicle in the first follicular wave of the cycle reached a diameter > or =5 mm, leaving at least one corpus luteum and one ovulatory-sized follicle in the remaining ovary. Ovulation rate per ewe was 50% higher in the ULO ewes compared with the control ewes at the end of the cycle during which surgery was performed, but it did not differ between groups at the end of the cycle, 2 mo later. This compensation of ovulation rate in ULO ewes was due to ovulation of follicles from the penultimate follicular wave in addition to those from the final wave of the cycle. Ovulation from multiple follicular waves appeared to be due to a prolongation of the static phase of the largest follicle of the penultimate wave of the cycle. Interestingly, the length of the static phase of waves was prolonged in ULO ewes compared with control ewes in every instance where the length of the static phase could be determined. Changes in follicular dynamics due to ULO were not associated with alterations in FSH and LH secretion. In conclusion, ovulatory compensation in ULO sheep involves ovulation from multiple follicular waves due to the lengthened static phase of ovulatory-sized follicles. These altered antral follicular dynamics do not appear to be FSH or LH dependent. Further studies are required to examine the potential role of the nervous system in the enhancement of the life span of the ovulatory-sized follicles leading to ovulatory compensation by the unpaired ovary in ULO sheep.     

Insulin like growth factor 1 and regulation of ovarian function in mammals

Various growth factors have been proposed to play endocrine and/or paracrine role in mammalian ovarian follicular development. The insulin like growth factor 1 (IGF-1) is one such factor. More and more reports now support the existence of an intra-ovarian IGF system including receptors and binding proteins. The role of IGF-1 in ovary is to amplify gonadotropin hormone action in terms of increased steroidogenesis by ovarian granulosa cell and granulosa cell proliferation. The synthesis and proteolysis of insulin like growth factor binding proteins, under the control of follicle stimulating hormone, regulate the intra-follicular availability of IGF-1, which further determines the sensitivity of granulosa cells to gonadotropins. Besides gonadotropins, IGF-1 has been implicated in somatotropin hormone action in the ovarian function. Exact mechanism of IGF-1 action in the ovarian follicles needs to be worked out to elucidate whether or not IGF-1 is indispensable in addition to know endocrine factors like gonadotropic and ovarian steroid hormones. This will pave the way for better understanding of control(s) which ensure final development of dominant follicle(s) and atresia of other follicles of the cohort.     

Effects of ovarian tissue reduction on the menstrual cycle: persistent normalcy after near-total oophorectomy

These experiments were designed to evaluate whether removal of approximately 95% visible ovarian tissue would interrupt the short- or long-term regulation of cyclic ovarian function. On cycle Days 2 4 (onset of menses = Day 1), the entire left ovary and approximately 90% of the right ovary were removed from three cycling cynomolgus monkeys. After approximately 95% ovariectomy, there was an acute elevation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which lasted 11 +/- 2 days. A midcycle-like gonadotropin surge occurred 20 +/- 3 days following approximately 95% ovariectomy; the next menses occurred 19 +/- 1 days later. Follicular phase patterns of estradiol preceded the midcycle gonadotropin surge, and luteal phase progesterone levels indicated subsequent ovulation. Two of three monkeys resumed normal menstrual cyclicity in the following cycle with follicular phase, luteal phase, and menstrual cycle lengths similar to pretreatment levels. Histological examination of the ovarian remnant removed on Day 21 of the next cycle revealed a morphologically normal corpus luteum and many small follicles. A second group of 6 rhesus monkeys also underwent approximately 95% ovariectomy for long-term evaluation of menstrual cyclicity; typical 28-day menstrual cycle patterns were observed in 4 of the 6 monkeys for 5 mo, with 2 of these 3 animals maintaining regular menstrual cycles for 1 yr. In summary, our data suggest that normal ovarian function, i.e. recruitment, selection, and dominance of the ovulatory follicle, ovulation, and subsequent corpus luteum function, is maintained with only approximately 5% of functional ovarian tissue remaining.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post partum patterns of circulating FSH, LH, prolactin, estradiol, and progesterone in nonsuckling cynomolgus monkeys.

Circulating levels of FSH, LH, prolactin (Prl), estradiol (E), and progesterone (P) were determined by RIA in four intact and four monkeys luteectomized (CLX) at parturition in order to a) characterize the patterns of these hormones during the puerperium, and b) examine a possible inhibitory role of the "rejuvenated" corpus luteum (CL) on the resumption of follicle growth post partum. In both groups during the first four weeks, FSH and LH were at tonic levels typical of ovulatory cycles. Recurrent puerperal "surges" of FSH, but not LH, unaccompanied by increments in serum E, were observed in both intact and CLX monkeys. No consistent pattern of serum Prl was apparent. CLX was followed by a prompt fall in serum P levels, which were elevated above typical follicular phase levels into the second week post partum in intact monkeys. Menstrual cycles resumed 2-4 months after delivery. Hormonal patterns during the first menstrual cycle post partum were indistinguishable from those observed in pregravidic ovulatory cycles. The findings indicate that in nonsuckling cynomolgus monkeys a) although it secretes progesterone, the puerperal CL does not inhibit the resumption of the ovarian cycle post partum, b) the puerperal ovary is not absolutely refractory to gonadotropins, since initial trials with Pergonal + hCG stimulated ovarian function, and c) ovarian activity during the puerperium may be limited by factors other than the tonic supply of gonadotropins.     

Effects of FGA and PMSG on follicular growth and LH secretion in Suffolk ewes

The effects of fluorogestone acetate (FGA) and/or pregnant mare serum gonadotrophin (PMSG) on follicular growth and LH secretion in cyclic ewes were determined. Suffolk ewes (n = 40), previously synchronized with cloprostenol were divided into 4 experimental groups (n = 10 ewes per group). Group I served as the control, while groups II, III and IV received FGA, PMSG, FGA and PMSG respectively. Four ewes of each group underwent daily laparascopy for 17 d. All the ovarian follicles >/= 2 mm were measured, and their relative locations were recorded on an ovarian map in order to follow the sequential development of each individual follicle. Comparisons were made of the mean day of emergence and the mean number of small, medium and large follicles, the atresia rate and the ovulation rate. For each group, 3 waves of follicular growth and atresia were observed during the cycle. During luteal phase, FGA treatment accelerated the mechanisms of follicular growth but reduced the number of large follicles and increased the atresia rate. In the follicular phase, FGA treatment was detrimental to both the number of large follicles and the ovulation rate. By contrast, PMSG enhanced recruitment of small follicles and the ovulation rate. Serial blood samples were collected during the luteal and follicular phases to study LH secretion. None of the treatments had any effect on LH secretion patterns.     

The temporal relationship between patterns of LH and FSH secretion, and development of ovulatory-sized follicles during the mid- to late-luteal phase of sheep

The aim of the present study was to investigate the temporal relationship between the secretory pattern of serum LH and FSH concentrations and waves of ovarian antral follicles during the luteal phase of the estrous cycle in sheep. The growth pattern of ovarian antral follicles and CL were monitored by transrectal ultrasonography and gonadotropin concentrations were measured in blood samples collected every 12 min for 6 h/d from 7 to 14 d after ovulation. There were two follicular waves (penultimate and final waves of the cycle) emerging and growing during the period of intensive blood sampling. Mean and basal LH concentrations and LH pulse frequency increased (P < 0.001) with decreasing progesterone concentration at the end of the cycle. Mean and basal FSH concentrations reached a peak (P < 0.01) on the day of follicular wave emergence before declining to a nadir by 2 d after emergence. None of the parameters of pulsatile LH secretion varied significantly with either the emergence of the final follicular wave or with the end of the growth phase of the largest follicle of the penultimate wave of the cycle. However, mean and basal LH concentrations did increase (P < 0.05) after the end of the growth phase of the largest follicle of the final follicular wave of the cycle. Furthermore, the end of the growth phase of the largest follicle of the final wave coincided with functional luteolysis. In summary, there was no abrupt or short-term change in pulsatile LH secretion in association with the emergence or growth of the largest follicle of a wave. We concluded that the emergence and growth of ovarian antral follicles in follicular waves do not require changes in LH secretion, but may involve changes in sensitivity of ovarian follicles to serum LH concentrations.     

Role of the double luteinizing hormone peak, luteinizing follicles, and the secretion of inhibin for dominant follicle selection in Asian elephants (Elephas maximus)

Elephants express two luteinizing hormone (LH) peaks timed 3 wk apart during the follicular phase. This is in marked contrast with the classic mammalian estrous cycle model with its single, ovulation-inducing LH peak. It is not clear why ovulation and a rise in progesterone only occur after the second LH peak in elephants. However, by combining ovarian ultrasound and hormone measurements in five Asian elephants (Elephas maximus), we have found a novel strategy for dominant follicle selection and luteal tissue accumulation. Two distinct waves of follicles develop during the follicular phase, each of which is terminated by an LH peak. At the first (anovulatory) LH surge, the largest follicles measure between 10 and 19.0 mm. At 7 ± 2.4 days before the second (ovulatory) LH surge, luteinization of these large follicles occurs. Simultaneously with luteinized follicle (LUF) formation, immunoreactive (ir) inhibin concentrations rise and stay elevated for 41.8 ± 5.8 days after ovulation and the subsequent rise in progesterone. We have found a significant relationship between LUF diameter and serum ir-inhibin level (r(2) = 0.82, P < 0.001). The results indicate that circulating ir-inhibin concentrations are derived from the luteinized granulosa cells of LUFs. Therefore, it appears that the development of LUFs is a precondition for inhibin secretion, which in turn impacts the selection of the ovulatory follicle. Only now, a single dominant follicle may deviate from the second follicular wave and ovulate after the second LH peak. Thus, elephants have evolved a different strategy for corpus luteum formation and selection of the ovulatory follicle as compared with other mammals.     

Seasonal variation in ovarian histology of the viviparous lizard Sceloporus torquatus torquatus

Changes in ovarian histology during the reproductive cycle of the viviparous lizard Sceloporus torquatus torquatus are described. In general, the variation in follicular histology observed during the seasonal cycle is similar to that of other lizards. Sceloporus t. torquatus exhibits a cycle in which small, previtellogenic follicles exist in the ovary from December to August. Vitellogenesis occurs between September and November, followed by ovulation from late November to early December. Parturition occurs the following spring. After ovulation, the remaining follicular cells form the corpus luteum and luteolysis did not occur until April-May. Follicular atresia is commonly observed in previtellogenic follicles with polymorphic granulosa, but occurs less frequently in follicles during late vitellogenesis. There are two germinal beds in each ovary. The yolk nucleus is evident in young oocytes as is a vacuolated ooplasma prior to vitellogenesis. Extensive polymorphism is observed in yolk platelets. Mast cells and secretory cells are observed in the thecal layer of the follicular wall as are melanocytes in the ovarian stroma. © 1995 Wiley-Liss, Inc.     

The ability of subordinate follicles of the second follicular wave to become dominant is lost by day 15 of the estrous cycle in cattle

Generally, unilateral ovariectomy before a critical period in the latter part of the estrous cycle induces a transitory increase in plasma FSH, which causes subordinate follicles to develop and maintain ovulation rates characteristic of the species. A limiting period for subordinate follicles to assume dominance and from which ovulation occurs has not been shown for cattle. Growth and/or regression of subordinate follicles were characterized following removal of the dominant follicle at different days of the luteal phase of the estrous cycle in cattle in this study. In the mid-luteal phase (Day 13 or 15), the ovary with the dominant follicle of the second wave was ablated via unilateral ovariectomy; the corpus luteum also was removed. In the late luteal phase (Day 17 or 19), the dominant follicle was ablated with an ultrasonically guided 20 gauge needle. When the dominant follicle was removed on Day 13, the largest subordinate follicle of the second wave of follicular development became dominant and ovulation occurred from this follicle in 4 of 4 animals. However, when the dominant follicle was removed on Day 15, 17 or 19, a new wave of follicular development was induced in 14 of 15 animals. Moreover, the recovered subordinate follicle of the second wave of follicular development had similar growth characteristics to naturally occurring dominant follicles. In conclusion, the subordinate follicle in the second follicular wave in cattle retained the ability to become dominant, but this ability was lost by Day 15 of the estrous cycle. However, cattle then were able to maintain ovulation by developing a new wave of follicular growth.     

Expression of follicle stimulating hormone and luteinizing hormone receptors during follicular growth in the domestic cat ovary

In order to better understand the pituitary regulation of follicular growth in the domestic cat, follicle stimulating hormone (FSH) and luteinizing hormone (LH) receptors (R) were localized and quantified in relation to follicle diameter and atresia using in situ ligand binding on ovarian sections. Expression of FSHR was homogeneous and restricted to follicle granulosa cells from the early antral stage onwards, whereas expression of LHR was heterogeneous on theca cells of all follicles from the early antral stage onward, and homogeneous on granulosa cells of healthy follicles larger than 800 microm in diameter and in corpora lutea. LHR were also widely expressed as heterogeneous aggregates in the ovarian interstitial tissue. Atretic follicles exhibited significantly reduced levels of both FSHR and LHR on granulosa cells, compared with healthy follicles whatever the follicular diameter, whereas levels of LHR on theca cells were lower only for atretic follicles larger than 1,600 microm in diameter. In healthy follicles, levels of FSHR and LHR in all follicular compartments increased significantly with diameter. Although generally comparable to that observed in other mammals, the expression pattern of gonadotropin receptors in the cat ovary is characterized by an early acquisition of LHR on granulosa cells of growing follicles and islets of LH binding sites in the ovarian interstitial tissue.     

Pattern of growth of dominant follicles during the oestrous cycle of heifers

Ovarian follicular development was studied in 13 heifers by daily ultrasound examination during 2 complete and consecutive natural oestrous cycles. In 21 cycles (81%) 3 dominant follicles were identified, in 4 cycles (15%) 2 and in the remaining cycle 1 (4%). Consistently, the first dominant follicle was detected on average on Day 4, reached a maximum size on Day 6, went through a period of relative stability between Days 6 and 10, then began to decrease in size and was undetectable by Day 15. The second dominant follicle was detected by Day 12, reached maximum size on Day 16 (or 19 in the 4 cycles in which the 2nd dominant follicle was the ovulatory follicle) and was undetectable by Day 19. The 3rd (ovulatory) follicle was identified on average by Day 16 (range Days 10 to 19) and maximum size was reached on Day 21. The ovulatory follicles were larger (P less than 0.05) than the previous ones and the stage of the cycle at which maximum size was reached was significantly different for each dominant follicle (P less than 0.05). The analysis of the rates of growth and atresia suggest that the rate of growth is slowest during mid-cycle. The number of dominant follicles that developed in the ovary ipsilateral to the corpus luteum was greater (P less than 0.05) than in the contralateral ovary.     

Time of ovarian follicular recruitment in cyclic pony mares

An experiment was carried out on pony mares to establish the time of the oestrous cycle at which ovarian follicles are recruited for ovulation. In one group (n=7), the cycle was interrupted at the preovulatory stage by removing the preovulatory follicle; in another group (n=13) the cycle was interrupted at day 6 of the luteal phase by inducing luteolysis with a prostaglandin injection (PG). In a subgroup (n=7) of those given PG, the ovary not bearing the corpus luteum was removed at the time of injection. A further group (n=6) served as surgical controls. The interval to the next ovulation and blood concentrations of FSH were observed. Anaesthesia alone induced in preovulatory mares was followed by normal ovulation 2.5+/-1 days later. Removal of the preovulatory follicle delayed the next ovulation (14.6+/-2.1 days; P < 0.01). Following PG injection, the interval to ovulation was similar regardless of whether an ovary was removed (12.8+/-4.3 days) or not (10+/-4.1 days). This similarity occurred despite a large and prolonged rise in plasma FSH levels that occurred only in the hemiovariectomized group. In addition, the intervals found after PG injection did not differ from those found after ablation of the preovulatory follicle. These observations indicate that 1) in the presence of the early active corpus luteum or dominant follicle, follicles grow to a similar stage of development; 2) recruitment of the follicle due to ovulation occurs 12 to 14 days before ovulation; 3) limiting new follicular growth to one ovary does not affect the time course to ovulation; and 4) prolonged high FSH levels do not alter the time course or ovulation rate.     

Ascorbic acid in buffalo ovary in relation to oestrous cycle.

Concentration of ascorbic acid was determined in different parts of buffalo ovary at four different stages of oestrous cycle viz. early luteal, mid luteal, late luteal and follicular. The stages were decided from the physical and morphological examinations of corpora lutea. The ovary was dissected in three components viz. corpus luteum, follicular fluid and ovarian stromal tissue for ascorbic acid assay. Corpus luteum showed significant change in concentration of ascorbic acid with the advancement of oestrous cycle, value being highest in late- luteal stage. Follicular fluid and ovarian stromal tissue did not show significant changes in ascorbic acid at any stage of the oestrous cycle. Small follicles, irrespective of the stage of oestrous cycle had, however, significantly higher ascorbic acid content than large follicles.     

Role of intrafollicular regulators and FSH in growth and development of large antral follicles in sheep

Manipulation of circulating concentrations of hormones and ovarian follicle status was carried out on Day 11-12 of the oestrous cycle in sheep. All follicles visible on the ovary were ablated by cautery and ewes were treated with oestradiol or ovine follicular fluid (oFF) to suppress FSH or with PMSG to increase circulating gonadotrophic activity. One group underwent unilateral ovariectomy which greatly increased endogenous FSH and was the only treatment which significantly affected LH pulse frequency. The size distribution of antral follicles, the extent of atresia and the mitotic index of granulosa cells of follicles on Day 15 showed that (a) treatment with oFF inhibited the growth of follicles beyond 2 mm diameter by suppressing the mitotic index of the granulosa cells and (b) the concentration of FSH in peripheral plasma was related to the ability of small antral follicles to grow during the late luteal-early follicular phase of the cycle. Subsequently, it was demonstrated that oFF inhibits, in a dose-dependent manner, folliculogenesis sustained by PMSG in ewes on Days 12-15. Inhibition of folliculogenesis was represented by a decrease in those follicles greater than 4 mm, an increase in the relative proportion of follicles less than 2 mm, and minimal change in the average number of follicles visible on the ovarian surface, and a decrease in the mitotic index of granulosa cells of follicles less than 2 mm. There was no change in the extent of atresia.(ABSTRACT TRUNCATED AT 250 WORDS)