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PubMed1978

Cell-to-cell communication and ovulation. A study of the cumulus-oocyte complex.

Cell-to-cell communication was characterized in cumulus-oocyte complexes from rat ovarian follicles before and after ovulation. Numerous, small gap junctional contacts were present between cumulus cells and oocytes before ovulation. The gap junction are formed on the oocyte surface by cumulus cell processes that transverse the zona pellucida and contact the oolemma. The entire cumulus mass was also connected by gap junctions via cumulus-cumulus interactions. In the hours preceding ovulation, the frequency of gap junctional contacts between cumulus cells and the oocyte was reduced, and the cumulus was disorganized. Electrophysiological measurements indicated that bidirectional ionic coupling was present between the cumulus and oocyte before ovulation. In addition, iontophoretically injected fluorescein dye was tranferred between the oocyte and cumulus cells. Examination of the extent of ionic coupling in cumulus-oocyte specimens before and after ovulation revealed that ionic coupling between the cumulus and oocyte progressively decreased as the time of ovulation approached. In postovulatory specimens, no coupling was detected. Although some proteolytic mechanism may be involved in the disintegration of the cumulus-oocyte complex, neither the cumulus cells nor the oocyte produced detectable levels of plasminogen activator, a protease which is synthesized by membrana granulosa cells. In summary, cell communication is a characterisitc feature of the cumulus-oocyte complex, and this communication is terminated near the time of ovulation. This temporal pattern of the termination of communication between the cumulus and the oocyte may indicate that communication provides a mechanism for regulating the maturation of the oocyte during follicular development before ovulation.

Animals↗

PubMed1977

Evidence for an inhibitory dopaminergic and stimulatory noradrenergic hypothalamic influence on PMS-induced ovulation in the immature rat. II. A pharmacological analysis.

Pregnant mare's serum gonadotropin (PMS; 10 IU day 30)-induced ovulation was used as a model to study the effect of drugs interfering with monoamine neuro-transmission on CNS processes controlling ovulation. The drugs were administered during the critical period on day 32 and tubal eggs were counted in the morning of day 33. When injected during the critical period, dopamine (DA) receptor agonists such as apomorphine, ET 495, ergotamine, 2-bromo-alpha-ergocryptine, lergotrile and ergocornine inhibited ovulation, an effect which was counteracted by the DA receptor blocking agent, pimozide. However, by itself pimozide had no significant effect, whereas combined noradrenaline (NA) and DA receptor blocking agents such as chlorpromazine and clozapine inhibited ovulation. alpha- and beta-adrenergic blocking agents and drugs influencing 5-hydroxytryptamine (5-HT) neurotransmission did not affect ovulation. LH-RH removed the ovulatory blockade induced by ET 495 in the same dose-range as it removed pentobarbital-induced blockade of ovulation. Furthermore, ergocornine did not black ovulation after the critical period and was less effective when given prior to the critical period. Therefore it is likely that the DA receptor agonists act via a central action. Thus, the present findings give further support for the existence of a central inhibitory DA and facilitory NA mechanism in the control of PMS-induced ovulation in the immature female rat.

Animals↗

PubMed1977

Fertility, ovulation and maturation of eggs in mares injected with HCG.

Pony mares were observed from January to August for incidence of oestrus, duration of oestrus, length of the oestrous cycle and for ovulation and fertility after injection of HCG. From January to 15 May most mares showed oestrus but the duration of oestrus was quite variable and few mares ovulated in response to HCG. From 15 May to 17 August oestrous cycles were more regular and ovulation was induced within 40-50 h by an intramuscular injection of 1500-5000 i.u. HCG. Pregnancy was established by one mating at a fixed time after HCG in 20 of 69 mares. Degenerate eggs were recovered from the oviducts of anoestrous recently ovulated, mated, unmated and pregnant mares. The first polar body was formed before ovulation in 2 eggs and had not formed in 2 recently ovulated eggs flushed from the oviduct. The second polar body formed after sperm penetration 10-12 h after ovulation. After formation of pronuclei, the first cleavage division occurred at 20 h and the second at 32 h after ovulation. Oestrus was inhibited by progesterone administered by vaginal devices but occurred within 1-3 days in 12 of the 20 mares after withdrawal of the devices.

Animals↗

PubMed1979

[Mechanisms of ovulation in mammalian females].

The aim of this review was to briefly recapitulate the most important mechanisms involved in ovulation in the Mammals. The rabbit served as a model for the study of reflex ovulation. The triggering of ovulation by coitus was shown to be dependent on the activation of the hypothalamo-pituitary axis by sensory signals of multiple origin. The fundamental aspects of the hormonal and nervous machinery that governs spontaneous ovulation have been envisaged. The timing of LH ovulatory release and the mechanisms of action of this hormone at the ovarian level have been defined. Evidence was given that steroid hormones from ovarian and/or adrenal origin could evoke or modulate ovulatory processes. The structures responsible for both the tonic and clonic secretion of LH in subprimate and in primate mammals have been localized in the hypothalamus. The nervous endocrine mechanisms involving interactions between LHRH, neurotransmitters, prostaglandins and steroid hormones have been elucidated. Short loop feed back effects of pituitary hormones were shown to control LHRH secretion. Several examples were given attesting that the limbic system, the thalamus and the neocortex on one hand, and the environmental factors, on the other hand, were capable of modulating the activity of the hypothalamic structures implicated in the control of either ovulation or estrous rhythm regulation. An unitarian conception of the ovulatory mechanisms, based on the fact that coital-induced ovulation and estrogen-induced ovulation could occur in spontaneous and reflex ovulators respectively, has been proposed.

Adrenal Cortex↗

PubMed1979

Ovulation induction in amenorrheic women.

Seventy-six patients with primary or secondary amenorrhea who wished to conceive were treated with clomiphene citrate, 2-Br-alpha-ergocryptine, and/or human menopausal gonadotropins (hMG). Of these 71 patients who received clomiphene citrate, 39 (55%) ovulated. Of these 71 patients, 52 had withdrawal uterine bleeding following IM progesterone, and 38 (73%) ovulated; only 1 of the 19 who did not bleed ovulated (P less than 0.001). Ovulation occurred in the former group of patients whether or not they had galactorrhea. Of the 32 patients who failed to ovulate despite treatment with the maximal dose of clomiphene, 250 mg/day for 5 days, 26 received hMG-hCG. All 26 ovulated and 15 conceived. All 8 patients with amenorrhea-galactorrhea who were treated either primarily or secondarily with bromergocryptine ovulated, and 4 conceived. Therefore, the drug of choice for ovulation induction in amenorrheic patients depends on 1) the presence of withdrawal bleeding after progesterone and 2) the presence of galactorrhea. In all patients with progesterone withdrawal bleeding with or without galactorrhea, the initial treatment of choice is clomiphene citrate. In the absence of withdrawal bleeding, hMG should be administered if galactorrhea is absent, and bromergocryptine should be administered if galactorrhea is present.

Amenorrhea↗

PubMed1978

Hypothalamic and raphe serotonergic systems in ovulation control.

The role of hypothalamic and midbrain serotonergic systems in the control of ovulation in the rat has been investigated using 5,7-dihydroxytryptamine (5,7-DHT) lesioning in conjunction with desmethylimipramine pretreatment. Intracisternal injection of 5,7-DHT (100 or 200 microgram) produced a dose-dependent decrease in the incidence of ovulation induced by PMS gonadotrophin (PMSG; 8 IU sc on day 30). Intraventricular injection of 200 microgram 5.7-DHT via the lateral ventricles completely blocked PMSG-induced ovulation. After injection into either site, nonovulatory animals were in proestrus on day 33 and contained fluid-filled uteri. Intracerebral injection of 5,7-DHT into the dorsal or median raphe significantly decreased the numbers of animals induced to ovulate. The extent and specificity of these chemical lesions were evaluated in the suprachiasmatic (SNR) and arcuate-median eminence regions of PMSG-treated rats using an in vitro uptake model. A general feature of every case of inhibited ovulation was the significant decrease in uptake of serotonin in the SNR, indicating destruction of serotonergic inputs to this region. This suggests that serotonergic SNR input from the dorsal raphe region is essential to ovulation. Median raphe lesions appeared to be more extensive than dorsal raphe lesions, involving serotonergic projections to the arcuate-median eminence region. In addition, ascending noradrenergic projections to the SNR were significantly destroyed, also implicating these systems in ovulation control.

5,7-Dihydroxytryptamine↗

PubMed1977

[Ovulation induction by cyclofenil (author's transl)].

The ovulation-inducing action of cyclofenil was investigated in 135 sexually mature women aged 20--35 years. The patients were only included in the trial if no ovulation in 2 consecutive cycles with the following criteria: basal temperature, cervix score, ascorbic acid retention, basophil count, serum hormone levels, e. g. LH and progesterone and the estrogens in the 24-hour urine could be determined. Ovulation was only considered to have occurred when all the parameters named indicated it. The lack of ovulation was accompanied by amenorrhea in 21 of the 135 patients. The ovulation rate in the 241 cycles observed was 101, corresponding to 42%. In the 114 patients with anovulatory cycles, the ovulation rate in the 184 cycles observed was 95, corresponding to 50%. In the 21 amenorrheic patients, ovulation occurred 6 times in the 57 cycles observed. Nausea or vomiting occurred as side effects in only 2 cases.

Adult↗

PubMed1978

Induced ovulation, development of the corpus luteum, and tubal transport in the striped skunk (Mephitis mephitis).

Ovulatory pattern, development of the corpus luteum (CL), and early tubal transport are described for 6 unmated and 19 mated striped skunks (mephitis mephitis) killed after known copulation times. Ovulation is induced by copulation and occurs around 42 hours (range = 40--50 hours) after first insemination. Seventeen of 19 females killed between 36 hours and 19 days postcoitus had ovulated. Two females killed at 36 hours had not ovulated; however, their follicles showed preovulatory changes and were significantly larger (p less than 0.01) than those of unmated females. Six unmated females, killed during and three weeks after the normal breeding season, had not ovulated. Ovarian events, such as preovulatory changes, ovulation, and development of the corpus luteum (CL), are described for animals killed 36 hours to 19 days post-coitus. Maximum CL size occurred at 11 days post-coitus and coincided with the onset of embryonic migration and enlargement. Embryonic development reflected individual variation in ovulation times. The first polar body was extruded at ovulation and the second at fertilization. Pronuclear stages were predominant at 42 to 48 hours and 3 to 8-cell stages at 72 to 96 hours; morulae (containing up to 95 cells) entered the uterus at seven days. Blastocysts were observed first at 11 days when embryonic spacing and enlargement began. Implantation occurred by 19 days.

Animals↗

PubMed1977

Environmental influence on ovulation and embryonic development in Rana pipiens.

Environmental effects on ovulation and embryogenesis in Rana pipiens were assessed using both freshly-captured fall animals and laboratory-conditioned females which had undergone vitellogenesis in the laboratory. Frogs in both categories were divided into two groups. Ovulation was hormonally induced in one group of females prior to cold exposure and in the second group of animals following an 8-week-period at 4 degrees C with an 8L 16D photoperiod. The incidence of both ovulation and normal embryonic development was increased following exposure of the animals to low temperatures and short daylength. Those animals which only partially ovulated prior to cold treatment did not respond to hormone injections following the period of cold exposure. Examination of the ovaries of these females revealed a much greater degree of oocyte resorption than was found in frogs whose initial ovulation was induced only after exposure to cold temperatures. The administration of ovulation-inducing hormones prior to artificial hibernation may thus have initiated a phase of oocyte resorption which progressed even at 4 degrees C. The incidence of ovulation was similar in wild-caught and laboratory-conditioned females, but eggs from the latter showed a much lower percentage of development to Shumway stage 20. This effect may have been related to differences in the environmental factors to whcih the two groups were exposed during oogenesis.

Animals↗

PubMed1978

Temporal relationships of estrogen, progesterone, and luteinizing hormone levels to ovulation in women and infrahuman primates.

These studies were undertaken to ascertain the interval between the estrogen and LH peaks and ovulation in women, rhesus monkeys, and baboons. Estrogen, progesterone, and LH were measured by RIA. Ovulation was documented by visual examination of the ovaries, histology of the corpora lutea, and recovery of ova. The data for human subjects was based on a group of 23 normal women scheduled for surgical sterilization. Blood was drawn daily between 8:30 and 10:30 P.M. beginning on day 10 of the cycle. Surgery was performed 1 to 5 days after the LH peak. The hormonal findings were correlated with the histology of the corpus luteum. The mean interval from the estrogen peak to ovulation was 34 hours, the interval from the estrogen peak to the LH peak was 24 hours, and that from the LH peak to ovulation was 9 hours. In 46 rhesus monkey cycles and in 53 baboon cycles diagnostic serial laparoscopic examinations were initiated following the estrogen peak and repeated every 24 hours until ovulation was confirmed. The mean interval between the estrogen peak and ovulation was 34 hours in the monkey and 41 hours in the baboon. The intervals from the estrogen peaks to the LH peaks were 12 hours in the monkey and 23 hours in the baboon. The intervals from LH peak to ovulation were 22 hours in the monkey and 18 hours in the baboon. Plasma progesterone levels were significantly increased prior to the LH peak in all three species.

Adult↗

PubMed1975

The use of synthetic luteinizing hormone-releasing hormone in induction of ovulation.

Each of 14 anovulatory patients received a single injection of 150 micrograms of synthetic luteinizing hormone-releasing hormone (LH-RH) in one induced menstrual cycle. In two subsequent cycles, patients were pretreated with clomiphene before LH-RH injection. Four patients received LH-RH after pretreatment with human menopausal gonadotropin (HMG) in another cycle. In each cycle, gonadotropin release and ovulation were recorded. All patients had previously failed to ovulate when treated with large doses of clomiphene. No patient ovulated following injection of LH-RH alone, although five patients exhibited a good pituitary response. Nine patients ovulated when they received LH-RH after pretreatment with clomiphene, and one patient ovulated when pretreated with HMG. The diagnostic value of a single injection of LH-RH is not clear. In the present study, gonadotropin response to LH-RH was not an entirely accurate predictor of a patient's ovulatory response in any of the four cycles. On the other hand, when clomiphene-LH-RH was administered, a good response was associated with ovulation in that cycle. The exact role of LH-RH in inducing ovulation is unclear, but the results of using LH-RH in conjunction with clomiphene are encouraging enough to warrant continued use and further study.

Clomiphene↗

PubMed1978

Effects of hypothalamic deafferentation on ovulation and estrous cyclicity in the female guinea pig.

The effects of hypothalamic deafferentiation on the estrous cycle and ovulation were studied in the mature female guinea pig, a spontaneous ovulator with a true luteal phase. Animals were stereotaxically deafferentated using the Haláxz knife technique. (1) Large complete deafferentation of the medial basal hypothalamus (MBH; arcuate nucleus, median eminence (ME), and a ventral part of the ventromedial nucleus) did not block cyclic ovulation, although the cycle became slightly prolonged. (2) Small complete deafferentation which excluded the ventromedial nucleus from the MBH and partially damaged the arcuate nucleus in anovulation and constant closure of the vaginal membrane. (3) Large anterior deafferentation, which eliminated neural afferent from medial preoptic area (MPO), suprachiasmatic portion of the preoptic nucleus (POSC) and the anterior periventricular area to the MBH, was effective in blocking ovulation and inducing constant vaginal opening. In most of the cases, the knife passed rostral to the suprachiasmatic nucleus (SCN). (4) Small anterior deafferentation at the caudal border of the optic chiasma did not block ovulation if the arcuate nucleus and ME were intact, although the cycle sometimes became irregular. (5) Posterior deafferentation at the level of the mammillary bodies failed to interfere with cyclic ovulation. It is concluded that, in the guinea pig, the deafferentated MBH is capable of sustaining both tonic and phasic secretion of gonadotropins (Gns) necessary for maintenance of normal estrous cycles and ovulation. However, this function of the MBH may also be modulated by facilitatory and inhibitory influences arising from extrahypothalamic areas.

Afferent Pathways↗

PubMed1976

The interrelationship between progesterone and luteinizing hormone during the ovulation cycle of the hen (Gallus domesticus).

The existence of a circadian rhythm in the sensitivity of the hypothalamus of the laying hen to stimulation by progesterone was investigated by injecting 0.5 mg progesterone subcutaneously during the proposed period of maximum insensitivity. Following this treatment increases in plasma concentrations of both LH and progesterone were observed which were comparable to the spontaneous preovulatory rises in the plasma levels of the hormones. The ability of either progesterone or luteinizing hormone releasing hormone (LH-RH) to induce premature ovulation varied according to the stage of follicular development. Neither hormone was more than 28% effective when injected within 6.5 h of the previous ovulation, whereas both hormones were 100% effective approximately 27 h after the terminal ovulation of a clutch sequence. Failure to ovulate in response to LH-RH given 6.5 h after ovulation was associated with a lack of progesterone secretion. Both LH and progesterone were secreted when ovulation was induced by injections of either LH-RH or progesterone, and LH was secreted in response to progesterone given 6.5 h after ovulation. These results demonstrate that progesterone stimulates the secretion of LH and LH stimulates the secretion of progesterone. The precise physiological role of these two hormones, however, was not established.

Animals↗

PubMed1975

The morphology of follicular development and ovulation in non-human primates.

A colony of Macaca fascicularis have been under continuous observation for the past 4 years to ascertain the follicular morphological changes that occur prior to ovulation and during the development of the corpus luteum. Of 609 experimental cycles, laparoscopy was performed at least once in 44-5% of the cycles. Of the 104 cycles where the ovulatory status was definitely known, 89-4% were deemed ovulatory and 10-6% anovulatory. The presence or absence of ovulation in the previous cycle did not have an effect on the cycle length either for the total cycles or when analysing only cycles over 28 days. Similarly, the occurrence of two consecutive ovulations (in consecutive cycles) on the same vs. opposite ovaries did not have a significant effect on the cycle length. Neither laparoscopic stress or anaesthesia effected the normal cyclicity of the animals. The characteristic changes in follicular morphology are most clearly defined in M. fascicularis. In this species the 24 of 36 hr prior to ovulation are accompanied by discrete changes which occur in a fixed sequence, allowing one to predict the time of ovulation with reasonable accuracy. In S. sciureus ovulation is preceded by extensive bulging at the follicular apex and haemorrhaging at the base of the follicle. Due to this haemorrhaging post-ovulatory follicles in S. sciureus are generally more easily discernible than in fascicularis. The formation of clear areas (stigma) is not as evident in either S. sciureus or G. senegalensis as in the macaque. Actual ovulation has been observed four times in M. fascicularis and twice in S. sciureus.

Animals↗

PubMed1979

Precoital single doses of delta9-tetrahydrocannabinol block ovulation in the rabbit.

delta9-Tetrahydrocannabinol (delta9-THC) inhibits pituitary gonadotropin secretion in castrated rhesus monkeys. Also, delta9-THC blocks the ovulatory reflux in rabbits. We report now the dose-response relationship of precoital single doses of delta9-THC on luteinizing hormone (LH) release and ovulation in the rabbit. Forty-five female rabbits in estrous were divided into nine groups of five animals. Groups 1 to 5 received a single intramuscular dose of delta9-THC (5,2.5, 1.25, 0.612, and 0.306 mg/kg, respectively) 2 hours before mating; animals of group 6 received vehicle only. In animals of groups 7 and 8 ovulation was induced with 100 IU of human chorionic gonadotropic (hCG), given intravenously 2 hours after the administration of delta9-THC (5 mg/kg) or vehicle. Rabbit luteinizing hormone (rLH) was measured in plasma 90 to 120 minutes after coitus or hCG administration. After the injection of 5 mg of delta9-THC, luteinizing hormone-releasing factor (LH-RF) (20 microgram intravenously) was administered to the animals of group 9. All animals of groups 6, 7, and 8 ovulated. A dose-response curve was observed in the animals treated with delta9-THC and natural mating. Whereas none of the animals treated with 5 or 2.5 mg/kg ovulated, one of the group treated with 1.25 mg/kg, two of the group treated with 0.612 mg/kg, and all treated with 0.312 mg/kg ovulated. Ovulations correlated with postcoital levels of rLH. All animals of group 9 ovulated, indicating that the site of action of delta9-THC is suprapituitary, probably hypothalamic.

Animals↗

PubMed1978

In vitro reversal of indomethacin-blocked ovulation by prostaglandin F2alpha.

An in vitro perfused ovary preparation was used to study the role of prostaglandin F2alpha (PGF2alpha) in follicle rupture. The administration of PGF2alpha alone has been shown to restore indomethacin-blocked ovulation in rabbits and monkeys. In the model used, ovulation consistently occurred when human chorionic gonadotropin (hCG) was given to the intact rabbit prior to ovarian removal. hCG-induced ovulation was blocked in both perfused and in situ control ovaries by indomethacin (10 mg/kg intravenously 6 hours after hCG) given to the intact animal. The addition of PGF2alpha (1 mg/200 ml) to the perfusion fluid restored ovulation in the isolated ovary as compared with the in situ ovary (P less than 0.005) and with the perfused, untreated ovary (P less than 0.01). Following removal and perfusion of both ovaries from rabbits treated with indomethacin, ovulation occurred following the addition of PGF2alpha to the perfusate, but did not occur without PGF2alpha (P less than 0.05). These data indicate that indomethacin can block ovulation and that ovulation can be restored by the addition of PGF2alpha to the perfusion system, further supporting the significance of PGF2alpha in the process of follicular rupture.

Animals↗

PubMed1975

Current research in coitus-induced ovulation: a review.

Against the background of renewed interest in the existence of reflex ovulation in many animal species and the possibility of its existence in man, this review on current research efforts embraces the multitude of nervous influences and stimuli accompanying cohabitation. Species showing reflex ovulation are not restricted to those using this as the sole ovulatory mechanism, but include also so-called facultative ovulators, which seem to use this mechanism as a last resort to assure reproductive capacity under adverse situations (rat); and species which for the length of the standing heat period become temporarily induced ovulators for the optimal coordination of all necessary steps to assure fertility (cattle, pig, sheep); and species in which frequent cohabitation (rat) or a single coitus after artificial insemination (sheep) assures either optimal ovulation or conception rates. Copulation might not always be essential; some of the cohabitation-related reflexes might be transmitted by olfactory, ocular, tactile and acoustic stimuli; emotions may play a role. These stimuli are transmitted to the CNS from the periphery by afferent nervous pathways, and are translated in the thalamic-hypothalamic-pituitary complex into neurohormonal phenomena, causing ovulation; or may cause, mainly by LH and/or oxytocin discharge, an acceleration or augmentation of processes involved in spontaneous ovulation. Intensive biochemical and pharmacological studies have unveiled some of the neurohormonal mechanisms involved in the hypothalamus and how these stimuli are transmitted to the pituitary or received at the ovarian level, as hormonal or neurohormonal phenomena.

Amenorrhea↗

PubMed1977

Plasma hormones in human gonadotropin induced ovulation.

Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone (E1), estradiol-17beta(E2), progesterone (P), androstenedione (A), and testosterone (T) were analyzed in daily plasma samples of seven cycles of human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) induced ovulation. Plasma FSH rose gradually and remained at a higher level (20 to 30 mlU/ml) during hMG injection while LH stayed at a low tonic level. The FSH/LH ratio of plasma gonadotropins was consistently higher than 1 in spite of injecting an hMG preparation with FSH/LH ratio of 1. A pharmacologically induced high RSH/LH ratio in the late follicular phase is contradictory to the low ratio seen in the normal ovulatory cycle. This may be one of the causes of multiple follicular maturation and ovulation frequently encountered in the hMG-hCG induced ovulation. Higher than normal levels of plasma progesterone commonly seen in the hMG-hCG induced cycle is attributed to the multiple ovulation. Plasma androgen levels, both A and T, in these therapy cycles stayed consistently within normal range. This is a strong contrast to the clomiphene induced cycle in which A and T were frequently elevated in parallel with elevated LH. No significant differences in plasma hormones were observed between the pregnant and nonpregnant patient following hMG-hCG induced ovulation. A consistent and similar ovarian response to hMG-hCG was noted in 1 individual who had 3 consecutive therapy cycles studied. The plasma hormone levels in the multiple ovulation did not show a significant difference from those in the single ovulation with the exception of a higher plasma P level in the former.

Adult↗