Recombinant FSH-induced follicle development in immature rats treated with an LHRH antagonist: a direct effect of RU486 on follicular atresia

1996 ◽  
Vol 150 (1) ◽  
pp. 85-92 ◽  
Author(s):  
J Th J Uilenbroek ◽  
P Kramer ◽  
E C M van Leeuwen ◽  
B Karels ◽  
M A Timmerman ◽  
...  
Keyword(s):  
Direct Effect ◽  
Ovarian Function ◽  
Female Rats ◽  
Follicle Development ◽  
Follicular Atresia ◽  
Antral Follicles ◽  
Serum Lh ◽  
Tenfold Increase ◽  
Immature Rats ◽  
Lhrh Antagonist

Abstract To investigate whether the progesterone antagonist RU486 has a direct effect on ovarian function, it was administered to immature female rats rendered hypogonadotrophic by administration of an LHRH antagonist and in which follicle development was stimulated by recombinant human FSH (recFSH). In the first experiments the effects of LHRH antagonist and recFSH on follicle growth were evaluated. Female rats of 22 days of age were injected with an LHRH antagonist (Org 30276; 500 μg/100 g body weight) every other day. This treatment resulted in a tenfold decrease in serum LH concentrations and a twofold decrease in serum FSH concentrations at day 30 and caused a reduction in the number and size of antral follicles. Treatment with recFSH (Org 32489) twice daily from day 26 for 4 days in a total dose ranging from 5 to 20 IU/animal increased the number and size of antral follicles in a dose-related manner and resulted after 20 IU recFSH in a tenfold increase in the concentration of inhibin in serum and ovaries at day 30. Once it was established that LHRH antagonist treatment in immature rats could be used to study the effects of gonadotrophins or steroids on follicle function, this animal model was used to study the effects of RU486 on the ovary. RU486 was administered (twice daily for 4 days, 1 mg/injection) to LHRH antagonist-treated rats in which follicular growth and differentation were stimulated by 10 IU recFSH or by 10 IU recFSH plus 0·5 IU human chorionic gonadotrophin (hCG). RU486 had no effect on circulating levels of LH and FSH, but stimulated follicular atresia both in rats treated with recFSH alone and in rats treated with recFSH and hCG. Inhibin concentrations both in serum and ovaries were significantly increased after hCG treatment. RU486, however, did not increase inhibin in the rats treated with recFSH and in those treated with recFSH and hCG. In summary, the present study has demonstrated that (1) immature rats treated with an LHRH antagonist can be used to study the effects of gonadotrophins and steroids on follicular function and (2) RU486 has a direct stimulatory effect on follicular atresia. Journal of Endocrinology (1996) 150, 85–92

SERUM GONADOTROPHINS AND FOLLICULAR DEVELOPMENT IN IMMATURE RATS AFTER EARLY ANDROGEN ADMINISTRATION

1976 ◽  
Vol 68 (3) ◽  
pp. 461-468 ◽  
Author(s):  
J. TH. J. UILENBROEK ◽  
E. ARENDSEN DE WOLFF-EXALTO ◽  
M. A. BLANKENSTEIN
Keyword(s):  
Testosterone Propionate ◽  
Follicle Stimulating Hormone ◽  
Follicular Development ◽  
Female Rats ◽  
Vaginal Opening ◽  
Follicular Growth ◽  
Antral Follicles ◽  
Follicular Maturation ◽  
Immature Rats ◽  
Plasma Oestradiol

SUMMARY Follicular development and serum gonadotrophin levels were studied in female rats after neonatal androgen administration. After injection of 1250 μg testosterone propionate (TP) on day 5 after birth the composition of the follicular population was altered: at nearly all ages the number of pre-antral follicles (follicular volume 2–20 × 105 μm3) was lower than in oil-treated rats, in some cases the number of small antral follicles (21–249 × 105 μm3) was also lower. Furthermore levels of serum follicle-stimulating hormone and luteinizing hormone were decreased from day 7 to day 20 suggesting that the high gonadotrophin levels before day 20 are of importance for normal follicular development. In contrast, final follicular maturation in TP-treated rats was enhanced; at day 35 more large antral follicles (follicular volume ≥ 500 × 105μm3) were present in TP-treated rats than in oil-treated rats. The presence of more large antral follicles was accompanied by higher plasma oestradiol concentrations, higher uterine weights and advanced vaginal opening. These results demonstrate an inhibition of normal follicular growth and an acceleration of ovarian maturation after neonatal androgen administration.

scholarly journals Follicle development, endocrine profiles and ovulation rate in adult Merino ewes: effects of early nutrition (pre- and post-natal) and supplementation with lupin grain

Reproduction ◽  
2014 ◽  
Vol 147 (1) ◽  
pp. 101-110 ◽  
Author(s):  
C Viñoles ◽  
B L Paganoni ◽  
K P McNatty ◽  
D A Heath ◽  
A N Thompson ◽  
...  
Keyword(s):  
Early Life ◽  
Ovarian Function ◽  
Ovulation Rate ◽  
Aromatase Activity ◽  
Follicle Development ◽  
Short Term ◽  
Antral Follicles ◽  
Cell Numbers ◽  
Metabolic Hormones ◽  
The Third

In adult ewes, we tested whether ovarian function, including the response to short-term supplementation, was affected by the nutrition of their mothers during the pre-/post-natal period. A 2×2 factorial design was used with nutrition in early life (low or high) and a 6-day supplement (with or without) as factors. All ewes received three prostaglandin (PG) injections 7 days apart, and the supplement (lupin grain) was fed for 6 days from 2 days after the second until the third PG injection. We measured reproductive and metabolic hormones, studied follicle dynamics (ultrasonography), and evaluated granulosa cell numbers, aromatase activity and oestradiol (E2) concentrations in follicular fluid in healthy follicles at days 3 and 7 of supplementation. Ovulation rate was increased by 25% by exposure to high pre-/post-natal nutrition (1.5 vs 1.2; P<0.05), in association with a small decrease in FSH concentrations (P=0.06) and a small increase in insulin concentrations (P=0.07). The number of healthy antral follicles was not affected. Acute supplementation increased the number of granulosa cells (3.7±0.2 vs 3.0±0.2 million; P<0.05) in the largest follicle, and the circulating concentrations of E2 (4.6±0.3 vs 3.9±0.3 pmol/l; P<0.05) and glucose (3.4±0.03 vs 3.3±0.03 mmol/l; P<0.01). Both early life nutrition and acute supplementation appear to affect ovulation rate through changes in glucose–insulin homoeostasis that alter follicular responsiveness to FSH and therefore E2–FSH balance.

Inhibition of first ovulation: administration of an LHRH antagonist to immature female rats

1987 ◽  
Vol 112 (3) ◽  
pp. 407-415 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
W. A. van Cappellen ◽  
G. A. Schuiling
Keyword(s):  
Chronic Administration ◽  
Female Rats ◽  
High Dose ◽  
Corpora Lutea ◽  
Vaginal Opening ◽  
Immature Female ◽  
Subcutaneous Injections ◽  
Antral Follicles ◽  
Preovulatory Follicles ◽  
Lhrh Antagonist

ABSTRACT Subcutaneous injections of an LHRH antagonist (ALHRH; Org.30093) were administered to immature female rats. Neither a single high dose (50 μg) nor repeated daily doses of 5–30 μg ALHRH/day, administered between 28 and 38 days of age, influenced the age and body weight at the time of vaginal opening or first ovulation. If repeated daily doses of 2 × 10 μg ALHRH were given from 32 to 42 or from 37 to 47 days of age, first ovulation was delayed by 3·0 and 6·3 days respectively. Administration of 10 μg ALHRH at 09.00 h and again at 17.00 h on the day of first pro-oestrus was found to be sufficient to block the expected first ovulation in 36 out of 38 rats. This effect could be repeated by administering the same doses of ALHRH at pro-oestrus and again on the next day: ovulation was blocked in eight out of eight rats. A single dose of 10 μg ALHRH, administered on the morning of pro-oestrus, blocked ovulation in five out of twelve rats. Both the preovulatory LH and FSH surge, as measured at 16.00 h on pro-oestrus, were found to be inhibited by ALHRH treatment. On the day after pro-oestrus no recruitment of new small antral follicles had occurred in rats with ovulatory blockade. Delayed ovulation took place 2–5 days after ALHRH injection at pro-oestrus; until 3 days after injection rats were able to ovulate their original preovulatory follicles, thereafter newly developed follicles ovulated and large ovarian cysts were found in the ovaries, next to fresh corpora lutea. Chronic administration of two injections daily of 10 μg ALHRH from 34 days of age until the morning of first pro-oestrus had marginal effects on the timing of first pro-oestrus and on follicle dynamics. It was concluded that with the ALHRH compound used, and in chronic as well as in acute experiments, first ovulation could only be delayed by its administration on the day of first pro-oestrus and that the effect was due to acute inhibition of the preovulatory gonadotrophin surge. J. Endocr. (1987) 112, 407–415

Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats

1984 ◽  
Vol 105 (3) ◽  
pp. 308-313 ◽  
Author(s):  
David R. Mann ◽  
Michael S. Blank ◽  
R. Sridaran ◽  
V. Daniel Castracane ◽  
Charles Eldridge ◽  
...  
Keyword(s):  
Serum Testosterone ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Constant Infusion ◽  
Simultaneous Treatment ◽  
Serum Lh ◽  
Gonadotrophin Secretion ◽  
Immature Rats ◽  
Lh Secretion

Abstract. The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25–26 days of age, and an Alzet osmotic minipump containing ACTH (1–24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 μg/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 μg of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 ± 94 vs 443 ± 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats. These data suggest that the inhibitory effect of ACTH on LH secretion in immature rats is mediated by an oestrogenic steroid, since this action can be blocked by simultaneous treatment with a low dose of the anti-oestrogen, nafoxidine.

Neonatal superior ovarian nerve transection inhibits follicle development by enhancing follicular atresia and suppressing granulosa cell proliferation in rats

2010 ◽  
Vol 22 (7) ◽  
pp. 1148 ◽  
Author(s):  
Xiaoxin Zhang ◽  
Lei Zhang ◽  
Shuying Huo ◽  
Jianlin Wang ◽  
Sheng Cui
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Sympathetic Nerve ◽  
Ovarian Function ◽  
Hormone Secretion ◽  
Neonatal Rat ◽  
Ovary Development ◽  
Follicle Development ◽  
Follicular Atresia ◽  
Superior Ovarian Nerve

The ovarian sympathetic nerves participate in the regulation of mammalian ovarian function, but it is still not known whether the neonatal ovarian sympathetic nerve is involved in follicular development and related mechanisms. In the present study, the superior ovarian nerve (SON) of the neonatal rat was transected on postnatal day (PD) 2, and follicle development, ovarian hormone secretion, ovulation rate, granulosa cell proliferation and apoptosis were analysed on PD 30 and PD 90. The results demonstrate that SON transection decreases follicle number and size, reduces ovulation induced by gonadotrophin and enhances follicular atresia. Bromodeoxyuridine (BrdU) and cleaved caspase-3 immunohistochemistry staining provide evidence that SON transection inhibits granulosa cell proliferation and promotes granulosa cell apoptosis. In addition, SON transection increases serum oestradiol levels, but has no influence on serum progesterone levels. These results suggest that the sympathetic nerve supply to the ovaries is important in regulating follicle development and ovary function. These results are critical for further understanding of the neuroendocrine regulation of ovary development and function, although the mechanism needs to be elucidated in future studies.

The ovary and sexual maturation of the brain

Development ◽  
1967 ◽  
Vol 17 (1) ◽  
pp. 1-10
Author(s):  
W. N. Adams Smith
Keyword(s):  
Corpus Luteum ◽  
Direct Effect ◽  
Sexual Maturation ◽  
Ovarian Function ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Female Rats ◽  
Corpora Lutea ◽  
Litter Mate ◽  
The Brain

Pfeiffer (1935, 1936) reported the induction of constant oestrus in female rats following the transplantation of testes from litter-mate males just after birth and noted that the ovaries of these animals did not contain corpora lutea. These changes remained after removal of the testis transplants. The same effects were obtained by Bradbury (1941) following the administration of multiple doses of testosterone propionate. Barraclough & Leathern (1954) found that a single injection of 1 mg of testosterone propionate at 5 days of age led to permanent sterility in female mice, with no corpus luteum formation in their ovaries. Similar results were obtained in rats by Barraclough (1961) with the administration of a single injection of 1·25 mg of testosterone propionate. This permanent change in ovarian function does not appear to be a direct effect upon the ovary (Bradbury, 1941).

scholarly journals Regulation of Follicular Atresia by WIP1-Mediated Apoptosis and Autophagy

2021 ◽  
Author(s):  
Su Zhou ◽  
Yueyue Xi ◽  
Yingying Chen ◽  
Wei Yan ◽  
Meng Wu ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Granulosa Cells ◽  
Ovarian Reserve ◽  
Ovarian Function ◽  
Signal Pathway ◽  
Follicle Development ◽  
Follicular Atresia ◽  
Wip1 Phosphatase

Abstract Female endocrine homeostasis and reproductive success depend on the number and quality of follicles. The follicle is the basic functional unit within mammalian ovaries. Excessive follicular atresia is responsible for the accelerated ovarian aging process. Therefore, exploring the molecular mechanism of follicle development and atresia is essential for protecting ovarian function. In this study, we interrogate the striking correlation between follicular atresia and wild-type p53-induced phosphatase 1 (WIP1) expression in mouse ovaries to understand how WIP1 phosphatase activity regulates follicle development. WIP1 is mainly expressed in granulosa cells of healthy growing follicles, and atretic follicles exhibit significantly weaker WIP1 expression compared with the healthy ones. Our in vivo study indicates that inhibition of WIP1 phosphatase activity causes endocrine disorder, fertility decline and decreased ovarian reserve by triggering excessive follicular atresia through promoting autophagy and apoptosis. By in vitro follicle culture, we determine that inhibiting the WIP1 activity impairs the follicle development, causing more follicular atresia and decreased oocyte quality. Besides, downregulating WIP1 expression in granulosa cells in vitro also promotes apoptosis and autophagy via WIP1-p53 and WIP1-mTOR signal pathway. Our findings from the in vitro and in vivo experiments revealed that appropriate Wip1 expression is required for follicle development. Downregulation of WIP1 expression accelerates follicle atresia via WIP1-p53 and WIP1-mTOR signal pathway related apoptosis and autophagy. It is speculated that moderate up-regulation of WIP1 expression may help delaying the decline of ovarian reserve.

scholarly journals Ovarian function in ewes made hypogonadal with GnRH antagonist and stimulated with FSH in the presence or absence of low amplitude LH pulses

1998 ◽  
Vol 156 (1) ◽  
pp. 213-222 ◽  
Author(s):  
BK Campbell ◽  
H Dobson ◽  
RJ Scaramuzzi
Keyword(s):  
Gnrh Antagonist ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Venous Blood ◽  
Hormone Secretion ◽  
Follicle Development ◽  
Ovarian Follicle Development ◽  
Antral Follicles ◽  
Low Amplitude ◽  
Experimental Group

This study examined the effect of LH pulses, of similar amplitude and frequency to those found in the luteal phase, on the pattern of hormone secretion and follicle development in GnRH antagonist-suppressed ewes stimulated with exogenous FSH. This experiment was conducted on ewes with ovarian autotransplants in a continuous study. Follicle development was suppressed in 18 ewes by 3 weeks of GnRH antagonist treatment (50 micrograms/kg per 4 days s.c.), and was then stimulated by infusion of ovine (o)FSH (5 micrograms NIADDK-oFSH-16/h i.v.) for 3 days. In addition to FSH, 10 animals received pulses of LH (2.5 micrograms NIADDK-oLH-26 i.v.) every 4 h for the entire period of the FSH infusion. The follicle population was determined by daily ultrasound. Samples of ovarian and jugular venous blood were collected at 4-h intervals over the period of the FSH infusion and there were three periods of intensive blood sampling (15-min intervals for 2.5 h at 24, 48 and 72 h after the start of the FSH infusion) when the steroidogenic capacity of the follicles in all 18 ewes was tested around an LH challenge (2.5 micrograms i.v.). GnRH antagonist treatment resulted in a 57% decrease in FSH concentrations and prevented ovarian follicle development beyond 3 mm in diameter. Infusion of FSH resulted in a 60% increase in FSH concentrations and stimulated the development of large antral follicles and a coincident increase in ovarian androstenedione, inhibin and oestradiol secretion in both experimental groups. In the absence of 4-hourly LH pulses basal steroid secretion was negligible (< 1 ng/min; P < 0.001). Daily LH challenges, however, revealed no difference in the steroidogenic capacity of the follicle population in either experimental group. Similarly, LH pulses had no effect on the growth rate and number of antral follicles stimulated by FSH infusion, or the pattern of ovarian inhibin secretion. In conclusion, these results show that while FSH alone can stimulate the development of ovulatory sized follicles in ewes made hypogonadal with GnRH antagonist, physiological patterns of LH stimulation have no deleterious effects on FSH-stimulated follicle development and are essential for normal steroidogenesis.

Changes in the characteristics of pulsatile luteinizing hormone secretion during the oestrous cycle and after ovariectomy and oestrogen treatment in female rats

1982 ◽  
Vol 94 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Takashi Higuchi ◽  
Masazumi Kawakami
Keyword(s):  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Luteinizing Hormone Secretion ◽  
Oestrogen Treatment ◽  
Serum Lh ◽  
Lh Release

Changes in the characteristics of LH secretory pulses in female rats were determined in different hormonal conditions; during the oestrous cycle and after ovariectomy and oestrogen treatment. The frequency and amplitude of the LH pulses were stable during the oestrous cycle except at oestrus when a pattern could not be discerned because of low LH concentrations. These were significantly lower than those measured during other stages of the cycle. Mean LH concentrations and LH pulse amplitudes increased with time up to 30 days after ovariectomy. The frequency of the LH pulse was unchanged 4 days after ovariectomy when mean LH levels had already increased. The frequency increased 10 days after ovariectomy and then remained stable in spite of a further increase in mean serum LH concentrations. Oestradiol-17β injected into ovariectomized rats caused a decrease in LH pulse amplitude but no change in pulse frequency. One day after treatment with oestradiol benzoate no LH pulse was detectable, probably because the amplitude was too small. A generator of pulsatile LH release is postulated and an oestrogen effect on its function is discussed.

scholarly journals Involvement of hyaluronan synthesis in ovarian follicle growth in rats

Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Noriyuki Takahashi ◽  
Wataru Tarumi ◽  
Bunpei Ishizuka
Keyword(s):  
Ovarian Follicle ◽  
Primary Site ◽  
Corpora Lutea ◽  
Follicular Atresia ◽  
Follicle Growth ◽  
Adult Rats ◽  
Antral Follicles ◽  
Cell Layers ◽  
Ha Synthase

Most of the previous studies on ovarian hyaluronan (HA) have focused on mature antral follicles or corpora lutea, but scarcely on small preantral follicles. Moreover, the origin of follicular HA is unknown. To clarify the localization of HA and its synthases in small growing follicles, involvement of HA in follicle growth, and gonadotropin regulation of HA synthase (Has) gene expression, in this study, perinatal, immature, and adult ovaries of Wistar-Imamichi rats were examined histologically and biochemically and byin vitrofollicle culture. HA was detected in the extracellular matrix of granulosa and theca cell layers of primary follicles and more advanced follicles. Ovarian HA accumulation ontogenetically started in the sex cords of perinatal rats, and its primary site shifted to the intrafollicular region of primary follicles within 5 days of birth. TheHas1–3mRNAs were expressed in the ovaries of perinatal, prepubertal, and adult rats, and the expression levels ofHas1andHas2genes were modulated during the estrous cycle in adult rats and following administration of exogenous gonadotropins in immature acyclic rats. TheHas1andHas2mRNAs were predominantly localized in the theca and granulosa cell layers of growing follicles respectively. Treatments with chemicals known to reduce ovarian HA synthesis induced follicular atresia. More directly, the addition ofStreptomyceshyaluronidase, which specifically degrades HA, induced the arrest of follicle growth in anin vitroculture system. These results indicate that gonadotropin-regulated HA synthesis is involved in normal follicle growth.

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