Effect of reduced ovarian tissue on cyclicity, basal hormonal levels and follicular development in old rats

Reduction of the number of growing follicles was proposed to contribute to the decline in reproductive performance with aging (Butcher and Page, 1981). To investigate the effects of a reduced number of follicles, rats which maintained regular estrous cycles at greater than 1 yr of age had either unilateral ovariectomy (ULO) or control surgery. Irregular estrous cycles and periods of constant estrus were more frequent during a period of 90 days after ULO than in controls. Follicle-stimulating hormone (FSH) concentration in plasma collected at 0900-1100 h of the metestrus nearest to 20, 50, and 90 days after surgery was increased by ULO; in both treatment groups, FSH increased between 20 and 90 days. Compensation in ovarian weight and number of corpora lutea had occurred by 90 days after ULO. Estradiol, estrone and luteinizing hormone (LH) concentrations did not change with time or treatment. Numbers of small, medium and large antral follicles per ovary at metestrus were increased by ULO, while the number of follicles per rat was decreased. It was concluded that the reduction in ovarian tissue (which decreased the number of growing follicles) resulted in an elevation of basal FSH followed by irregularity in estrous cycles.     

Compensatory ovarian hypertrophy in the long-term hemicastrate rat: size distribution of growing and atretic follicles

In the intact rat, on estrus, the follicle-stimulating hormone (FSH) surge recruits nearly twice the correct number of follicles for ovulation, then, on metestrus, the excess follicles undergo atresia. In contrast, in the long-term hemicastrate rat, the FSH surge recruits fewer antral follicles on estrus, but there is little atresia on metestrus. To determine if fewer follicles are recruited by the FSH surge of long-term hemicastrates because the pool of follicles capable of responding to the FSH is smaller than in intact rats, preantral, antral, atretic, and healthy follicles were counted in ovaries of rats killed on each day of the estrous cycle. In general, there were only half as many healthy preantral follicles per rat in hemicastrates compared with intacts. There were an equal number of large antral follicles per rat in hemicastrates compared with intacts. Thus, compensatory hypertrophy did not extend to preantral follicles but was evident in large preovulatory follicles. These results suggest that fewer follicles are recruited on estrus in hemicastrate rats because fewer follicles are at the appropriate stage of development to respond to the FSH surge.     

Unilateral ovariectomy increases loss of primordial follicles and is associated with increased metestrous concentration of follicle-stimulating hormone in old rats.

The primary objective of these studies was to determine whether unilateral ovariectomy (ULO) would affect rate of loss of primordial follicles. In experiment 1, retired breeder rats, unilaterally ovariectomized and maintained on the experiment for 90 days after surgery, had fewer (p less than 0.01) primordial follicles per ovary than sham-operated controls of the same age. The purpose of experiment 2 was to determine whether time after ULO or age of rats was the critical factor necessary for increased loss of primordial follicles found after ULO in experiment 1. It was found that age was more important than time: when ULO was performed at 30 days of age, the number of primordial follicles did not decrease in ULO rats compared to controls (p greater than 0.05) before 250 days of age. Concentrations of FSH during metestrus were not greater (p greater than 0.05) in ULO rats than in controls until rats were 250 days old. There were also fewer (p less than 0.05) growing follicles per ovary in ULO than in sham-operated rats at 250 days of age. It is concluded that ULO can increase the loss of primordial follicles, but only in old rats (greater than or equal to 250 days of age).     

Compensatory responses after unilateral ovariectomy in rabbits

Compensatory ovarian and gonadotropic responses to unilateral ovariectomy (ULO) were examined in the rabbit doe, an induced ovulator. On Days 2, 4, 5, 6, 8, 10, 15 and 20 after ULO, ovaries from 3 hemiovariectomized does and 1 sham-hemiovariectomized doe were examined macro- and microscopically for number, size and signs of atresia of follicles. The number of surface follicles increased initially to 7 or 8 follicles 2 days after ULO, followed by an increase to 10 or more follicles by Day 15 (control ovaries had 5.7 +/- 0.4 follicles). Total numbers of antral follicles and the proportion of follicles which were atretic did not vary relative to day after ULO. However, distributions of antral follicles in classes of 0.2-mm increments were significantly different between sham-ovariectomized and hemiovariectomized does after Day 2 due to shifts of follicles into larger size classes. Peripheral serum concentrations of follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), increased temporarily during the 48 h after ULO. Follicular compensation after ULO in the doe entailed nonlinear increases in numbers of preovulatory follicles, due to increased growth within the antral population of follicles, probably the result of an acute surge of FSH. A period of more than 10 days was necessary to restore the number of preovulatory follicles after ULO. Exogenous human chorionic gonadotropin (hCG) induced ovulation of recruited follicles.     

Influences of age and ovarian follicular reserve on estrous cycle patterns, ovulation, and hormone secretion in the Long-Evans rat

This study examined the influences of aging and reduced ovarian follicular reserve on estrous cyclicity, estradiol (E(2)) production, and gonadotropin secretion. Young virgin and middle-aged (MA) retired breeder female rats were unilaterally ovariectomized (ULO) or sham operated (control). Unilateral ovariectomy of young rats reduced the ovarian follicular reserve by one-half, to a level similar to that found in MA controls. Unilateral ovariectomy of MA females reduced the follicular pool further, to one half of MA controls. The incidence of regular cyclicity was significantly lower in MA ULO females than in young controls, with intermediate cycle frequency in young ULO and MA controls. Among cyclic rats, the magnitude of the proestrous LH surge was highest in young controls, intermediate in young ULO rats and MA controls, and lowest in MA ULO females. Similarly, ovulation rates were highest in young controls, intermediate in young ULO rats and MA controls, and lowest in MA ULO females. While young ULO rats exhibited augmented secondary FSH surges on estrous morning, middle-aged ULO females displayed secondary FSH levels comparable to young controls. The effects of age and reduced follicle number on estrous cyclicity and gonadotropin secretion were not due to altered E(2) secretion, as preovulatory E(2) levels were similar among all groups. Thus, experimental reduction in the follicular reserve exerts acute effects on the preovulatory LH surge, ovulation rate, and estrous cyclicity in both young and MA rats. However, decreased follicle number increases FSH levels only in young rats, indicating aging-related alterations in the feedback regulation of FSH.     

The differing responsiveness of the anterior- and the middle-anterior hypothalamic area to estradiol benzoate implant: inhibition of compensatory ovarian hypertrophy.

Estradiol benzoate (E2) was chronically implanted, unilaterally or bilaterally, for about 30 days in the anterior (A-AHA) or the middle (M-AHA) portion of the anterior hypothalamic area (AHA) of unilaterally ovariectomized (ULO) and intact cyclic rats. E2 unilaterally implanted in the A-AHA partially blocked and bilaterally implanted totally blocked compensatory ovarian hypertrophy (COH) in response to ULO. E2 implanted in the M-AHA induced ovarian atrophy in ULO rats. In M-AHA E2 implanted rats, ovulation was completely inhibited, vaginal smears became persistently cornified, serum FSH was drastically suppressed to 23-24% of the estrous level, LH was unremarkably changed. These effects were less pronounced when the implant was place in the A-AHA, i.e., ovulation was partially blocked only with bilateral implantation, vaginal cycles were irregular, serum FSH was suppressed to 66% and 44% of the estrous level after unilateral and bilateral implantation, respectively, LH was rather unchanged. Uteri were neither atrophic whether the implants was placed in the A-AHA or in the M-AHA. In normal cyclic rats, the effects of E2 implantation in the two areas were similar to those observed in ULO rats, except that the effects were evident even after unilateral implantation since the brain had not been compensated. The results allowed to indicate a functional subdivision of the ventral AHA, at least into the A-AHA and the M-AHA. The M-AHA was experimentally elucidated to be more estrogen sensitive than the A-AHA for monitoring of serum FSH, and was suggested to be involved in the episodic secretion of FSH. The inhibitory effect of estrogen on COH may primarily be mediated through the M-AHA and secondarily through the A-AHA.     

Effect of unilateral ovariectomy on compensatory ovarian hypertrophy, peripheral concentrations of follicle-stimulating hormone and luteinizing hormone, and ovarian venous concentrations of estradiol-17 beta in prepuberal gilts

A study was designed to characterize the compensatory ovarian response to unilateral ovariectomy (ULO) in prepuberal gilts and to investigate further the mechanisms involved in compensatory ovarian hypertrophy (COH). Forty-eight crossbred gilts were sham ovariectomized (Sham) or unilaterally ovariectomized at 130 days of age (Day 0). Remaining ovaries in ULO gilts were removed and Sham gilts were bilaterally ovariectomized 2, 4 or 8 days later. A peripheral blood sample was taken before surgery and ovarian venous blood samples were taken before removal of each ovary. Serum estradiol-17 beta (E2) concentrations were determined. Mean wet and dry ovarian weights per ovary on Day 2 for ULO and Sham gilts were 3.4 versus 2.8 and 0.26 versus 0.24 g, respectively. Those weights on Days 4 and 8 were greater (P less than 0.01) for ULO than Sham gilts. Follicular fluid weight per ovary was greater (P less than 0.05) for ULO than Sham gilts on Days 2, 4 and 8. Ovarian venous E2 concentrations were greater (P less than 0.01) for ULO than for Sham gilts on Days 2 and 4 but were similar on Day 8. In a second experiment, 42 prepuberal gilts 130 days of-age were subjected to Sham (n = 18), ULO (n = 18) or bilateral ovariectomy (BLO; n = 6) to evaluate follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion immediately after surgical treatment. Release of FSH within the first 24 h was greater for BLO than ULO and for ULO than Sham gilts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of unilateral ovariectomy and subsequent ovum implantation in mice.

Unilateral ovariectomy (ULO) was done on any stage of the cycle and the animals were mated within day 1 to day 21 to observe the acute and long term effect of ULO on ovum implantation. Implantation reduced in proportion to single ovary if the animals were mated within 24 hr of ULO. Increase in ovarian weight along with an increase in implantation number continued in mated mice and reached at peak on day 19-21 of ULO (sacrificed after 6 days i.e., 25-27 days of ULO). After ULO the remaining ovary compensated within day 5-6 of ULO even during pregnancy. Ovarian histology showed stimulation of small antral follicles in mice mated on day 3 of ULO (sacrificed after 6 days i.e., day 9 of ULO) along with a decrease of large antral follicles and pre-antral follicles. Preantral follicles were at peak on day 12-14. Large antral follicles attained a peak on day 4 which slowly decreased. The occurrence of implantation in such ULO conditions are discussed.     

Hysterectomy in the rat: surgical disruption of the vascular channels reduces number of ova shed.

Cycling rats were hysterectomized and/or unilaterally ovariectomized (ULO) on day 2 (metestrus). Collateral blood supply to the remaining ovary via the uterine artery was left intact or disrupted. Animals were killed in metestrus after one complete estrous cycle. Control rats were also killed at this time. Counts of tubal ova revealed that intact rats ovulated an average of 4.4 +/- 0.4 eggs per ovary (N = 8). Following ULO, rats (N = 8) ovulated 9.6 +/- 0.2 EGGS. Ligation of the uterine artery decreased the number of eggs ovulated in ULO rats (N = 8) to 5.4 +/- 1.1. Hysterectomized rats (N = 8) ovulated 4.8 +/- 0.5 eggs per ovary. If the blood supply was disrupted, a reduction to 2.7 +/- 0.2 eggs per ovary occurred (N = 8). Hysterectomized and ULO rats (N = 8) ovulated 10.3 +/- 0.4 eggs from the remaining ovary but only 5.0 +/- 1.0 eggs if the collateral blood supply of the uterine artery was not intact (N = 10). The results demonstrate that disruption of the vascular channels during the surgical procedures of hysterectomy and/or ULO results in a reduction of the expected ovulation number.     

Ovarian follicle dynamics in immature rats treated with a luteinizing hormone-releasing hormone antagonist (Org. 30276)

The high concentrations of gonadotropins present in immature female rats by the end of the second week of life were suppressed by treatment with an antagonist against luteinizing hormone-releasing hormone (LHRH-A; Org. 30276) on Days 6, 9, 12, and 15 of life. Differential ovarian follicle counts were made on Days 15, 22, 28, and on the day of first estrus of all growing follicles and follicles greater than or equal to 100 x 10(5) microns 3 (mostly antral). In LHRH-A-treated rats, a retardation of follicle growth was noted on Day 15, followed by a gradual loss of growing follicles that amounted to 20% on Day 22 and 40% on Day 28; at first estrus, the total population of growing follicles was only 50% of that present in control rats. Antral follicles, first present at 22 days of age, were lower in number at 28 days of age and at first estrus in LHRH-A-treated rats; this was true for both healthy and atretic follicles. Ovarian weights were significantly reduced in LHRH-A-treated rats at 15 and 28 days of age and on the day of first estrus. However, the numbers of corpora lutea following the first, and normally timed, ovulation were the same in both groups. It was concluded that for early recruitment of follicles to reach a full-sized pool of growing follicles at the age of puberty, high concentrations of gonadotropins early in life have a significant role.     

Follicular recruitment in long-term hemicastrate rats

In the long-term hemicastrate rat, the total number of ova shed during estrus is the same as in the intact rat. To determine if the dynamics of follicular development are the same in the hemicastrate rat as in the intact control rat, the remaining ovary was removed from rats 20 to 30 days after hemiovariectomy. Complete serial sections of each ovary were prepared for histological examination. All follicles greater than or equal to 300 micrometers were counted, measured, and examined for signs of atresia. Long-term hemicastrate rats had a total complement of half as many healthy antral follicles compared to intact rats at estrus. At metestrus, there were half as many small and medium antral follicles in long-term hemicastrates as in controls. However, the total number of large antral follicles was the same in hemicastrate and intact rats. Thus, by metestrus, the appropriate number of follicles for ovulation appears to have been achieved in both animals, with all these large antral follicles located in the one remaining ovary of the hemicastrate rat, while they are distributed between both ovaries of the intact rat. Ovaries of the long-term hemicastrate rats contained far fewer attretic follicles than ovaries of intact rats. These findings suggest that the process of follicular recruitment differs greatly between intact and long-term hemicastrate rats. Atresia of small and medium antral follicles (300-400 micrometers in diameter) is apparently a necessary step in achieving the correct number of ovulatory follicles in the intact rat, yet the hemicastrate rat arrives at the correct number of ovulatory follicles without atresia.     

Effect of a low dose of pregnant mare's serum gonadotropin on follicular recruitment and atresia in cycling rats

Atresia appears to play a central role in selecting the correct number of follicles for ovulation in the rat. A wave of atresia, apparent by noon on metestrus, reduces the number of large healthy follicles to the appropriate quota for ovulation. The purpose of this study was to test the hypothesis that falling levels of gonadotropin on the morning of estrus precipitate the wave of atresia of large follicles seen on metestrus. Endogenous concentrations of follicle-stimulating hormone (FSH) were augmented by a single injection of pregnant mare's serum gonadotropin (PMSG; 0.025 IU/gram body weight) administered at different times during the periovulatory period. Animals given PMSG at 0800 h on estrus (when the endogenous FSH surge was waning) had a supernormal number of large healthy follicles in their ovaries at 1200 h on metestrus. This increase in large healthy follicles was accompanied by a decrease in large atretic follicles in the ovaries. The same dose of PMSG, when administered at other times during the periovulatory period, did not affect any of the parameters measured. These observations suggest that the wave of atresia normally seen in large follicles on metestrus is triggered by the decline in the concentration of FSH during the morning of estrus and can be prevented by prolonging the surge of FSH with administration of PMSG.     

The effects of food restriction and hypophysectomy on numbers of primordial follicles and concentrations of hormones in rats

Three experiments were done to examine the effects of food restriction, beginning at 21 days of age, on loss of primordial follicles and on concentrations of gonadotropins and sex steroids in rats. In Experiment 1, food restriction (FR) from 21 to 51-55 days of age had no effect on number of primordial follicles, but increased the plasma concentration (p less than 0.05) of follicle stimulating hormone (FSH). (p less than 0.05). In Experiment 2, comparisons were made of groups of rats (1) fed ad libitum (AL) (2) hypophysectomized at 21 days of age and fed ad libitum (AL-HY), (3) food restriction from 21 to 52-58 days of age (FR), and (4) food restriction with twice-daily injections of follicular fluid (FR-FF). Hypophysectomy was the only treatment that decreased the loss of primordial follicles (p less than 0.001). Concentrations of FSH were decreased in AL-HY and increased in FR and FR-FF rats (144 +/- 13, 53 +/- 15, 275 +/- 30 and 359 +/- 56 ng/ml in AL, AL-HY, FR and FR-FF rats, respectively). Concentrations of luteinizing hormone (LH) were lower (p less than 0.05) in AL-HY, FR and FR-FF rats than in AL rats. In Experiment 3, AL and FR rats were unilaterally ovariectomized (ULO) at 30 days of age. Blood samples were taken 5 days prior to ULO, at ULO and at 12 h, 5 days, and 22-28 days after ULO.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of frozen ovarian autografts on compensatory ovulation and steroid production in unilaterally ovariectomized rats.

In the present study rats were unilaterally ovariectomized (ULO) and the surgically removed ovary was frozen for 13 days. After allowing the remaining ovary to compensate with respect to number of ova shed, the frozen graft was thawed and transplanted subcutaneously to determine the effect on ovulation number, cycle length, uterine weight, ovarian weight and plasma levels of estradiol-17beta (E2) and progesterone. Rats ULO at 45 days of age, which received an autograft 13 days later, had a decrease in the number of eggs shed as compared to control ULO rats (6.4 +/- 0.8 vs. 11.1 +/- 0.9 eggs, respectively) and a decrease in plasma E2 (14.5 +/- 1.7 VS. 21.0 +/- 1.5 PG/ML, respectively). No differences were observed in progesterone concentration, uterine weight, ovarian weight or cycle length. In contrast, rats ULO at 31 days of age, which received an autograft 13 days later, showed no differences in comparison to control ULO rats. Castrates which received ovarian autografts developed cycling vaginal smears and had increased E2 (31.9 +/- 4.3 pg/ml) and decreased progesterone (18.3 +/- 1.9 ng/ml) levels. Since ULO animals with autografts shed fewer ova, the present study demonstrates that the amount of ovarian tissue influences ovulation number either by utilization of gonadotropins or by an, as yet, undefined mechanism.     

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.     

Effects of a luteinizing hormone-releasing hormone antagonist in late-juvenile female rats: blockade of follicle growth and delay of first ovulation following suppression of gonadotropin concentrations

Subcutaneous injections of an antagonist against luteinizing hormone-releasing hormone (LHRH-A, Org, 30276) were administered to late-juvenile female rats. The effects on timing of vaginal opening and first ovulation on serum gonadotropin concentrations and on follicle growth were studied. The dose of 100 micrograms LHRH-A/100 g body wt, given on Days 28, 31, and 34, did not influence timing of first ovulation. After administration of 500 micrograms LHRH-A/100 g body wt, ovulation was retarded by 4.7 days if injections were given on Days 28 and 31; by 6.7 days if given on Days 28, 31, and 34; and by 11.5 days if given on Days 28, 31, 34, and 37. Serum LH and FSH concentrations 3 days after the first, second, and third injections of 500 micrograms LHRH-A were significantly (p less than 0.01) lower than in saline-treated controls. Ovarian follicle counts showed decreased numbers of (antral) Class 2, 3, and 4 follicles 3 days after injection of 500 micrograms LHRH-A/100 g body wt on Day 28; a significantly higher number of Class 1 follicles and a further decrease in Class 2, 3, and 4 follicles 3 days after the second LHRH-A injection; and total absence of Class 3, 4, and 5 follicles 3 days after the third LHRH-A injection. Six days after the third LHRH-A injection, Class 3 and 4 follicles reappeared in the ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal induction of ovulation stimulates atresia of antral follicles in a vespertilionid bat, Scotophilus heathi

Scotophilus heathi is a seasonally monoestrous subtropical vespertilionid bat found at Varanasi, India. Although the antral follicles remain present in the ovaries of S. heathi from November till March, ovulation is delayed in this species until early March. In order to understand the mechanism of ovulation suppression during this period of delayed ovulation, the effects of human chorionic gonadotropin (hCG), pregnant mare's serum gonadotropin (PMSG), follicle stimulating hormone (FSH) and gonadotropin releasing hormone agonist (GnRH agonist) on ovarian morphology and steroid concentration were investigated. Hormonal treatments were given as a single i.p. dose 24 h after capture. The bats were sacrificed 48 h after the injection. Treatment with hCG, PMSG, FSH and GnRH agonist failed to induce ovulation in S. heathi, although these hormones produced a high degree of ovarian stimulation. The administration of hCG and PMSG induced ovarian enlargement, intense hyperemia, marked changes in the interstitial cells (ICs), development of several antral follicles and a varying degree of abnormalities in the oocytes of most of the antral follicles. In the bats treated with hCG, PMSG and GnRH agonist, androstenedione concentration increased significantly to extraordinarily high levels, whereas estradiol concentration decreased. Administration of FSH caused regression of ICs and pyknosis of granulosa cells in the majority of antral follicles. FSH did not enhance androstenedione concentration. The results of the present study suggest that the failure of hormonal treatments to induce ovulation during the period of delayed ovulation might be due to a seasonal desensitization of ovarian follicles in S. heathi. The hormonal treatment instead stimulated the ICs to produce a high level of androstenedione resulting in atretic changes of the antral follicles.     

Effect of buffalo follicular fluid treatment on follicle population and ovulation rate in guinea pigs

A number of workers have studied the effect of follicular fluid (FF) on the secretion of follicular stimulating hormone (FSH) but little is known about its potential as a regulator of ovarian activity, including ovulation rate. This paper describes the effect of charcoal treated-buffalo follicular fluid (buFF) treatment on follicular growth and ovulation rate in guinea pigs. Eighteen guinea pigs in three groups of 6 each were given 0.2 ml buFF at 12 hr interval for 3 days at different stages of estrous cycle viz., early-luteal, mid-luteal or follicular phase. One control group received equal volume of saline. Estrus was monitored every morning and evening by inspection of the opening of vaginal membrane and its cytology. All animals were sacrificed at 24 hr after the onset of estrus. Both the ovaries were dissected out, weighed and number of ovulation points recorded. One ovary from each animal was processed for histological examination to determine the population of healthy and atretic follicles. In early-luteal and follicular phase-treated animals the onset of estrus was delayed (P < 0.01) and ovulation rate was not affected. However, estrus occurred at normal when the treatment was initiated at midluteal stage and 50% animals failed to ovulate in this group. The total follicle population at metestrus increased significantly in all treated animals because of increase in number of follicles of size class II (400 to < 600 microns diam.). Atresia was also declined due to treatment. These results demonstrated that the buFF contained some inhibitory substances that delayed the onset of estrus in guinea pigs.     

Follicle stimulating hormone secretion and compensatory ovarian hypertrophy in prepubertal ewes

A study was conducted to determine the effect of unilateral ovariectomy (ULO) on follicle stimulating hormone (FSH) secretion and compensatory ovarian hypertrophy in prepubertal ewes. Thirty-three ewe lambs were allotted according to age and weight to a control (C) or ULO group. In the C group, a sham ovariectomy was performed on day 0 and both ovaries were removed on day 7. In the ULO group, one ovary was removed on day 0 and the remaining ovary was removed on day 7. Blood samples were collected from the jugular vein via venipuncture at 0, 6, 12 and 24 hours after the time of sham surgery or ULO (day 0). Subsequent samples were collected daily until day 7, and all samples were assayed for FSH and LH. Unilateral ovariectomy increased (P<0.01) ovarian weight and follicular fluid weight; however, lyophilized ovarian weight was similar for both groups. Within the ULO group, removal of the ovary having the largest follicle(s) did not prevent an increase in ovarian weight or follicular fluid weight of the remaining ovary. Unilateral ovariectomy had no effect on the total number of follicles (1 to 6 mm) per ovary; however, the number of large (5 to 6 mm) follicles per ovary was increased (P<0.05) following ULO. By 12 hours after ULO there was a transient increase (P<0.05) in the circulating concentrations of FSH. Circulating concentrations of luteinizing hormone (LH) were either low or undetectable in these prepubertal ewes and no LH response was observed following ULO. These results indicate that compensatory ovarian hypertrophy in ULO prepubertal ewes is accompanied by a transient rise in circulating FSH concentrations.     

A possible dual mechanism of the anovulatory action of antiprogesterone RU486 in the rat

The purpose of these experiments was to investigate the mechanism of the anovulatory action of antiprogesterone RU486 (RU486) in rats by studying its effects on follicular growth, secretion of gonadotropins and ovarian steroids, and ovulation. Rats with 4-day estrous cycles received injections (s.c.) of either 0.2 ml oil or 0.1, 1, or 5 mg of RU486 at 0800 and 1600 h on metestrus, diestrus, and proestrus. At the same times, they were bled by jugular venipuncture to determine serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 beta-estradiol (E), and progesterone (P). On the morning of the day after proestrus, ovulation and histological features of the ovary were recorded. Rats from each group were killed on each day of ovarian cycle to assess follicular development. Rats treated similarly were decapitated at the time of the ovulatory LH surge and blood was collected to measure LH. The serum levels of LH increased and those of FSH decreased during diestrus in rats treated with RU486. Neither E nor P levels differed among the groups. Treatment with RU486 caused both a blockade of the ovulation and an increase in ovarian weight in a dose-dependent manner. At the time of the autopsy (the expected day of ovulation), rats treated with 1 mg RU486 had ovaries presenting both normal and post-ovulatory follicles and unruptured luteinized follicles. Rats treated with 5 mg RU486 presented post-ovulatory follicles without signs of luteinization. The number of follicles undergoing atresia increased in rats treated with RU486. Rats treated with 5 mg RU486 exhibited a significant decrease in ovulatory LH release. The mechanism by which RU486 produces the ovulatory impairment in rats seems to be dual: first, by inducing inadequate follicular development at the time of the LH surge and second, by reducing the amount of ovulatory LH released. The physiological events-decreased basal FSH secretion and follicular atresia-that result from use of RU486 cannot be elucidated from these experiments and should be investigated further.