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PubMed1978

A scanning electron microscopic study of the luteo-follicular complex. III. Repair of ovulated follicle and the formation of the corpus luteum.

As observed by SEM, the repair of an ovulated mammalian follicle is accompanied by a sequence of morphogenetic processes. In the initial phase, a mass of cells and coagulated fluids forms at the site of rupture. Shortly thereafter, connective cells, recruited from the adjacent and subjacent connective tissue stroma begin to proliferate and to migrate over this mass such that in the rabbit, the entire site of disruption is covered by a layer of connective cells by approximately 2 days following ovulation. Coincident with the migration of the connective tissue, superficial cells from undisturbed lateral and basal areas of an ovulated follicle also proliferate and begin to migrate over the newly established connective tissue matrix. By approximately 4 days following ovulation in the rabbit, the surface of an ovulated follicle is repopulated by elements of the superficial epithelium. The formation of the underlying corpus luteum (corpora lutea) involves characteristic morphological changes as granulosa cells transform into steroid secreting luteal cells. The luteal cells become organized into cords of cells which usually surround capillary vessels. When examined by SEM, the smooth-surfaced endoplasmic reticulum of the luteal cell is quite apparent and is observed to form a three-dimension network of anastomosing tubules which are continuous with the nuclear membrane. Variations in the appearance of the surface of the ovary which directly overlies corpora lutea were observed when the mouse, rat and rabbit were compared. The regression of corpora lutea involves the infiltration of the luteal mass by connective tissue and both degeneration and vacuolization of the luteal cells. The regressing corpus luteum is a honey-comb-like structure in which each space is occupied by a degenerating luteal cell.

Animals↗
PubMed1993

Inhibition of ovulation by a triphasic gestodene-containing oral contraceptive.

The minimal effective dose of gestodene for inhibition of ovulation was studied in 30 female volunteers. Daily doses of 10 micrograms to 50 micrograms gestodene were given orally for 21 days. A control cycle prior to treatment and a treatment cycle were monitored for LH, FSH, estradiol, progesterone and cervical score. At a daily dose of 40 micrograms of gestodene, 6/7 volunteers exhibited inhibition of ovulation and 1/7 had a cycle with luteal insufficiency. Ovulation was inhibited in all volunteers on 50 micrograms gestodene, suggesting that the minimum dose required to inhibit ovulation was 40 micrograms gestodene. Cervical score was blunted even at 10 micrograms gestodene. Similarly, 20 volunteers were treated with coated tablets containing ethinylestradiol/gestodene at 30/50 micrograms for 6 days, 40/70 micrograms for 5 days and 30/100 micrograms for 10 days. This triphasic gestodene-containing preparation inhibited ovulation in all 20 females. In one cycle in which follicle development was observed only 43 pg estradiol/ml was secreted. Data from this investigation suggest that this triphasic gestodene-containing OC has a high contraceptive efficacy.

Adult↗
PubMed1995

Genetic evidence that ovulation reduces sexual receptivity in Drosophila melanogaster females.

Drosophila females start ovulation shortly after mating, and at the same time they become unreceptive to courting males. Both physiological changes are induced by the "sex-peptide" derived from the male accessory glands. It is conceivable, therefore, that the first effect of the peptide is to induce ovulation, and some signal derived from ovulated eggs makes females unreceptive. To test this hypothesis, I examined the mating receptivity of virgin D. melanogaster females homozygous for lozenge mutants that showed a high-frequency spontaneous ovulation. These females were reluctant to mate. However, when mature eggs were genetically deprived using nonallelic female sterile mutants, their receptivity increased significantly, although mating speed was still slower than that of normal virgin females. Essentially the same was found with the females that were ectopically expressing the sex-peptide gene. The results indicate that ovulation induced by the sex-peptide has an effect of reducing the sexual receptivity of mated females.

Animals↗
PubMedDate not supplied

Naltrexone effect on pulsatile GnRH therapy for ovulation induction in polycystic ovary syndrome: a pilot prospective study.

The aim of the present study was to analyze the opioid influence on LH pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the effectiveness of a long-term opioid antagonist (naltrexone) treatment in improving the pulsatile GnRH therapy which is successful in this syndrome. Ten obese women affected by PCOS participated in the study. Patients were hospitalized during the early follicular phase and underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since pregnancies did not occurr in any patient, after spontaneous or progestin-induced menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally for 8 weeks and during treatment repeated the basal protocol study and the ovulation induction cycle with the same modalities. The naltrexone treatment significantly reduced the insulin response to OGTT and the LH response to GnRH bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning the ovulation induction by pulsatile GnRH, naltrexone treatment was able to improve, although not significantly, the ovulation rate (60% pre-treatment vs 90% post-treatment). Furthermore, the maximum diameter of the dominant follicle and the pre-ovulatory estradiol concentration were higher after long-term opioid blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post-treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs 986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile GnRH co-treatment two pregnancies occurred. In conclusion, our data show that naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian responsiveness to ovulation induction in obese PCOS patients when compared to pulsatile GnRH alone. This action seems to be related to a decrease of insulin secretion. Further randomized studies should be performed in order to obtain significant conclusions on the possible clinical application.

Adult↗
PubMed1981

The effect of prostaglandin synthesis inhibition by indomethacin on ovulation and ovum maturation in the in vitro perfused rabbit ovary.

Prostaglandins (PGs) have been implicated in the mechanism of ovulation in several species through the use of PG synthesis inhibitors such as indomethacin. Studies of ovulation in the in vitro perfused rabbit ovary have aided in the delineation of the process of ovulation. This study was designed to determine the effects of indomethacin on follicle rupture and ovum development in the in vitro perfused rabbit ovary preparation. Indomethacin treatment (0.5 microgram/ml) significantly reduced the occurrence of ovulation in gonadotropin-treated ovaries. The percentage of in vitro ovulated ova and ova recovered from unruptured follicles during ovarian perfusion which achieved Metaphase II did not significantly differ between indomethacin-treated and control ovaries (hCG alone). However, increased degeneration of Metaphase II ova was associated with indomethacin treatment. In in vitro culture experiments this degeneration could be prevented by supplemental PGF2 alpha. These results indicate that inhibition of PG synthesis by indomethacin prevents follicle rupture but does not affect ovum maturation, thus providing further evidence that these two processes are distinct phenomena in vitro.

Animals↗
PubMed1979

Dissociation of spontaneous and mating induced ovulation by frontal hypothalamic deafferentations in the rat.

Different types of anterior hypothalamic deafferentations have been used to investigate the nervous pathways involved in spontaneous and mating-induced ovulation in the rat. Knife cuts which circumscribed the suprachiasmatic nuclei on all but their ventral surface and either their rostral or caudal poles prevented spontaneous ovulation, but the rats were sexually receptive (copulation plugs and sperm in the smear), and mating induced ovulation. Similar types of cut extended dorsally so as to sever the continuity between the preoptic area and the mediobasal hypothalamus also prevented spontaneous ovulation, and although these rats were also receptive, mating did not induce ovulation. Two possible explanations are considered: either (i) that difference between the effects of the two types of cut is a direct function of the differing proportions of gonadotrophic hormone-containing axons severed, or (ii) cuts in the region of the suprachiasmatic nuclei specifically impair a mechanism for the maintenance of diurnal rhythms, to which the abnormality in gonadotrophin control is secondary.

Afferent Pathways↗
PubMedDate not supplied

Plasma progesterone levels during oestrous cycle and their relationship with the ovulation rate in Red Sokoto (Maradi) goats.

Twenty-five 2-3-year-old cycling does weighing 17-25 kg were obtained from semi-nomadic farmers and managed under controlled conditions while simulating the traditional management system. Oestrus was synchronized using progestogen impregnated vaginal pessaries. Blood samples were collected daily for progesterone assay from the day of pessary withdrawal up to one complete oestrous cycle. Oestrus was checked twice daily using vasectomized bucks. Ovulation rate was determined by direct observation of the ovaries following laparotomy on day 5-7 of the oestrous cycle. Following oestrus synchronization, mean ovulation rate was 1.68 +/- 0.13. Mean oestrous cycle length and duration of oestrus were 21.30 +/- 0.28 days and 21.37 +/- 0.24 hours respectively. Plasma progesterone concentrations ranged from non-detectable levels on the day of oestrus to 5.2 +/- 0.28 ng ml at mid-cycle. The duration of elevated progesterone level (greater than 2 ng/ml) was about 12 days. The peak progesterone values did not differ between animals with different ovulation rates. However, the plasma progesterone concentration during the early cycle (days 0-6) was significantly lower in the single ovulators compared with others. There were no major differences in plasma progesterone levels during the oestrous cycle of Red Sokoto does with different ovulation rates.

Animals↗
PubMed1994

Review of ovulation return upon discontinuation of once-a-month injectable contraceptives.

Once-a-month combined injectable preparations draw their contraceptive efficacy from continuous ovulation suppression. When their use is discontinued, ovulation resumes within a few weeks or a few months, depending on the formulation. After use of the dihydroxyprogesterone acetophenide 150 mg/estradiol enanthate 5 mg combination for one to two years, ovulation returns in most subjects 3-4 months after discontinuation of treatment. Similarly, recent data show that after 2-year use of the depot-medroxyprogesterone acetate 25 mg/estradiol cypionate 5 mg or the norethisterone enanthate 50 mg/estradiol valerate 5 mg combination, approximately 70% women have resumed ovulation by the third month post-treatment. This is shorter than the time for return of ovulation experienced by ex-users of progestogen-only injectable contraceptives.

Contraceptive Agents, Female↗
PubMed1986

Ultrasonic and endocrinologic investigation of ovarian follicle and free fluid in cul-de-sac for monitoring follicular development and ovulation.

The accuracy of ultrasound as a means of monitoring follicular development and ovulation detection was studied in 31 infertile women. The follicular diameter measured by ultrasound correlated well actual diameter found during laparotomy (r = 0.88), and estradiol-17 beta (E2) and progesterone in follicular fluid aspirated from large follicles (greater than or equal to 16 mm) indicated high levels. Furthermore, in 23 out of the 55 cycles, ultrasound examinations demonstrated free fluid in cul-de-sac at ovulation, and concentrations of E2 and progesterone (P) in peritoneal fluid by the puncture of cul-de-sac dramatically increased after ovulation. We suggested that ultrasound monitoring provided a reliable measure of follicular growth and prediction of ovulation, and a combined use of ultrasound and puncture of cul-de-sac could be developed into a new tool for the study of the mechanism of human ovulation.

Adult↗
PubMed1988

Gonadotropin-releasing hormone (GnRH) inhibits ovulation induced with luteinizing hormone (LH) in proestrous hypophysectomized rats.

In this paper we present evidence that a single low dose of the natural synthetic gonadotropin-releasing hormone (GnRH), inhibits ovulation induced by LH in proestrous-hypophysectomized rats. Rats hypophysectomized by the parapharyngeal route in the morning of proestrus received an intravenous injection of 100 or 300 ng GnRH at 1400 h immediately followed by 1.0 microgram LH per 100 g bw. In control groups, either one or both hormones were replaced with 0.9% NaCl. Ovulation was assessed the following morning by counting the ova present in oviductal flushings. All the rats treated with LH alone ovulated, and the addition of GnRH reduced significantly the number of ovulating rats and the number of ova per ovulating rat. In other groups of rats hypophysectomized in the morning of proestrus and treated in the same way, ovarian or adrenal secretory rates of estradiol and/or progesterone were measured after cannulation of the corresponding vein, in the afternoon of proestrus. In these animals, GnRH failed to inhibit either the ovarian progesterone surge observed 2 h after LH administration, or the adrenal progesterone secretion. All hypophysectomized rats showed lower ovarian secretory rate of estradiol than intact rats; this rate was not affected by treatment with LH or LH plus GnRH. The systemic estradiol levels in plasma of hypophysectomized rats were distributed within a range of 20 pg/ml to 50 pg/ml. The number of rats whose levels were above 21 pg/ml on estrus day was significantly higher in rats receiving 300 ng GnRH as compared to those receiving 100 ng GnRH, reaching values that surpassed the concentration found in intact, untreated animals at the same time of estrus. This effect did not depend on LH administration.

Adrenal Glands↗
PubMed1983

Induction of ovulation with human urinary follicle-stimulating hormone: endocrine pattern and ultrasound monitoring.

Nine infertile patients, suffering from polycystic ovaries, were treated with human urinary FSH and hCG (eight cases) to induce ovulation. Oestrone, oestradiol, 17 alpha-hydroxyprogesterone, testosterone and androstenedione serum levels increased during the treatment. A decrease in luteinizing hormone serum levels was noticed, and in five cases a spontaneous peak was observed. No changes were noted in 5 alpha-dihydrotestosterone serum levels. Ultrasound scanning of the ovaries often revealed multiple follicles at different speeds and stages of growth and their marked turnover was observed. The beginning of the LH spontaneous surge was precocious compared to the normal ovulating follicular sizes: it does not appear that an optimum size exists but when the LH peak occurred too prematurely, ovulation did not take place. Administration of hCG seems to be necessary as spontaneous peaks of LH are not always followed by rupture of the follicle. Ultrasound scanning plays an important role in monitoring ovulation induction, while oestradiol and 17 alpha-hydroxyprogesterone serum levels are not good indicators of follicular maturity in multifollicular growth. Ovulation occurred in eight patients; four conceptions were obtained, one of which resulted in abortion. No ovarian hyperstimulations were observed.

Adolescent↗
PubMed1994

Increased incidence of high-order and singleton conceptions after ovulation induction in winter.

The possible relationship between the season of conception after ovulation induction and high-order multifetal pregnancies, was investigated. From 1975 to 1989, 111 high-order multiple births after ovulation induction were recorded at the Chaim Sheba Medical Center. This group was compared with 142 singleton pregnancies that resulted from induction of ovulation during 1989. Composite monthly cohorts of high-order multifetal pregnancies were constructed for each month of the year, and the probability of such pregnancies was estimated. The period of ovulation induction and the day of presumed conception were noted. A statistically-significant increase in the probability of high-order and singleton conceptions occurred during the winter. Our observation indicates a seasonal pattern in high order and singleton conceptions after ovulation induction.

Adolescent↗
PubMed1986

Chronic gonadotropin-releasing hormone agonist treatment suppresses ovulation and sexual behavior in group-living female rhesus monkeys.

The sexual behavior of six adult rhesus females was observed with each of four males prior to, during, and following a 90 day treatment with 20 micrograms/day of a gonadotropin releasing-hormone (GnRH) agonist (WY-40972). All females ovulated, approached males and copulated during an untreated cycle. No ovulations occurred during agonist treatment and all females showed reduced sexual interest during the last 25 treatment days. Three females showed elevated estradiol and copulated during the first 10 days of agonist treatment, but never showed similar levels of estradiol or copulation during the rest of treatment. Within 34 days after agonist treatment, all females initiated proximity to males, copulated, and ovulated. All females became pregnant on their second ovulation after agonist treatment. This demonstration that inhibition of ovulation with a GnRH agonist decreased rhesus female sexual initiation, demonstrates the importance of ovarian hormones to female sexual motivation and suggests that the changes in human female sexual interest should be evaluated during the development of agonist-based contraceptives.

Animals↗
PubMedDate not supplied

Ovarian secretion of pregnane compounds at first ovulation in rats treated with pregnant mare's serum gonadotropin.

Progesterone, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH), 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-DHP), 20 alpha-hydroxy-5 alpha-pregnan-3-one (20 alpha, 5 alpha), and 5 alpha-pregnane-3 alpha, 20 alpha-diol (DIOL) in ovarian venous plasma at first ovulation in female rats treated on day 30 with 10 IU of pregnant mare's serum gonadotropin (PMSG) were assayed using gas chromatography. Progesterone peaked at late proestrus before ovulation (day 32) and at early diestrus after ovulation (day 34). With the first peak, 5 alpha-DHP and 3 alpha-OH increased. The 20 alpha-DHP level peaked at early diestrus after ovulation (day 34) and remained high thereafter. The 20 alpha, 5 alpha and DIOL peaked at estrus after ovulation (day 33) and then fell slowly. Injection of 2 micrograms of luteinizing hormone (LH) before sample collection increased secretion of 20-keto-pregnane compounds, except when they were at peak levels. The secretion of 20 alpha-hydroxy-pregnane compounds was unaffected by LH at all times tested. These results suggest that rat ovaries without corpora lutea secrete 20-keto-pregnane compounds in response to LH, but that 20 alpha-hydroxy-pregnane compounds are secreted only from ovaries with corpora lutea.

Animals↗
PubMed1987

Reduced estradiol production by a substituted triazole results in delayed ovulation in rats.

Ovulation in the rat is delayed by a single administration of the substituted triazole R151885 (1,1-di(4-fluorophenyl)-2-(1,2,4-triazol-1-yl)-ethanol). This delay results from a 24-hr shift in the preovulatory luteinizing hormone (LH) surge since administration of chorionic gonadotrophin on proestrus restores ovulation. Plasma levels of estradiol are markedly reduced (42-45%) 6-12 hr after administration of R151885. The restoration of ovulation in R151885-pretreated rats, by administration of exogenous estradiol benzoate, indicates that the reduced estradiol levels play a pivotal role in the delay of ovulation. Granulosa cells isolated from rat ovaries produce estradiol and progesterone in vitro in the presence of both follicle-stimulating hormone and testosterone. The addition of R151885 to such cultures results in a dose-dependent inhibition of estradiol production (69% by 1 microM) without a significant effect on progesterone production. This inhibition occurs at concentrations of R151885 similar to those measured in vivo. R151885 is a competitive inhibitor of human placental aromatase (apparent Ki with androstenedione substrate of 410 nM) and produces a type II spectral perturbation of cytochrome P-450 from placental microsomes. Pituitaries isolated from R151885-treated rats have reduced LH output in response to gonadotrophin-releasing hormone stimulation compared with those of controls. It is proposed that R151885 competitively inhibits aromatase activity in developing ovarian follicles. The resultant temporary reduction of plasma estradiol levels at a critical time in the estrous cycle, and consequent inadequate pituitary sensitization, produces a 24-hr delay in the preovulatory LH surge and hence ovulation is delayed by 24 hr.

Animals↗
PubMed1975

Effectiveness of prostaglandin f 2 alpha in restoration of HMG-HCG induced ovulation in indomethacin-treated rhesus monkeys.

Six mature female rhesus monkeys were treated with HMG-HCG in control cycles at doses adjusted to induce ovulation while avoiding superovulation. Occurrence of ovulation was determined by observation of fresh ovulation points at laparotomy 48 to 120 hours following HCG. In subsequent cycles animals were treated with indomethacin (treatment days 4 through 10) together with the established dose of HMG-HCG. In 8 cycles indomethacin 5 mg/kg was given i.m. once daily; in 9 cycles 10 mg/kg i.m. was administered in 2 divided doses. Following this, PGF2alpha (3 mg t.i.d. s.c.) was administered for 3 days together with indomethacin 10 mg/kg and HMG-HCG, beginning on the day prior to HCG. Determinations of progesterone were performed by RIA on treatment days 4, 7, 10, and 11. Eleven of the 13 control cycles were ovulatory. With indomethacin 5 mg/kg/day, 5 of 8 cycles were ovulatory but ovulation was delayed in 2 instances. Of 9 cycles using indomethacin 10 mg/kg/day only 1 was ovulatory. When PGF2alpha was administered in susequent cycles along with indomethacin (10 mg/kg) and HMG-HCG, ovulation occurred in 13 of 19 cycles. These data suggest that local ovarian PGF2alpha may be essential in the mechanics of follicle rupture in gonadotropin-treated rhesus monkeys.

Animals↗
PubMed1978

Effects of prostaglandin E2 and DL204 IT, an inhibitor of prostaglandin degradation, on ovulation and ovum transport in the hamster.

The effects of 2(3-ethoxyphenyl)-5,6-dihydro-s-triazole-[5,1-a]isoquinoline (L-11204 or DL 204 IT and PGE2 on ovulation and ova transport were studied. DI 204 IT was administered in doses of 0.2-25 mg/kg s.c. on the day of estrus. A smal reduction in ovulating follicles was observed 96 hours later, but only at the 5 mg/kg dose level. At all dose levels, however, DL 204 IT caused a dose-related reduction in the number of ova in the oviducts. PGE2 at a total dose of 2 mg/animal s.c., administered in 4 divided doses over the second and third day of the cycle did not affect ovulation or ova transport. PGE2 plus DL 204 IT (5 mg/kg), however, completely blocked ovulation in all but one animal. That animal had one ovulated follicle and a single ova was recovered from its oviduct.

Animals↗
PubMed1983

Ovarian and plasma PGE and PGF levels in naturally ovulating brook trout (Salvelinus fontinalis) and the effects of indomethacin on prostaglandin levels.

Plasma and ovarian levels of PGE and PGF were measured by radioimmunoassay in naturally ovulating brook trout (Salvelinus fontinalis). At 12 hours post-ovulation, PGF levels in plasma and ovarian tissue were significantly elevated over levels in gravid controls. Plasma PGF levels were still elevated 5-7 days post-ovulation. Indomethacin treatment (10 micrograms/gm body weight) of ovulatory brook trout significantly decreased plasma and ovarian PGF levels by 12 hours post-ovulation. No significant differences were observed in plasma PGE levels, though gravid controls contained significantly elevated ovarian PGE levels as compared to ovulated fish.

Animals↗