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A role for thyroid hormone in the induction of ovulation and corpus luteum function.

We have previously demonstrated that thyroid hormone synergizes with follicle-stimulating hormone (FSH) to exert stimulatory effects on granulosa cell differentiation and function, suggesting that it plays a physiological role in amplifying FSH-mediated differentiation of granulosa cells. The adequate differentiation of these cells, followed by normal follicle development, is indispensable for ovulation and subsequent corpus luteum formation. Thus, in the present studies, the clinical implications of thyroid hormone in the induction of ovulation and corpus luteum function were investigated. Serum levels of total 3,5,3'-triiodothyronine (T3) and total thyroxine (T4) as well as free T3 and T4 were significantly lower in patients with weight loss amenorrhea compared to normal cycling women. Although no ovulation was induced by clomiphene therapy when the serum T3 levels were less than 80 ng/dl, the rate of ovulation induced by clomiphene increased in parallel with the augmentation of serum T3 levels. This suggests that an adequate circulating level of thyroid hormone is one of the factors responsible for successful induction of ovulation by clomiphene citrate. Furthermore, the short luteal phase and insufficient progesterone secretion observed in patients with subclinical hypothyroxinemia were not improved by clomiphene therapy alone, but were improved markedly by combined treatment with thyroid hormone replacement and clomiphene citrate. These data imply that concomitant clomiphene treatment with thyroid hormone replacement therapy is of a great value not only for ovulation induction, but also for the treatment of luteal-phase defect in patients with subclinical hypothyroxinemia.

Adolescent↗

Induction of ovulation with the sole use of clomiphene citrate in late-onset 21-hydroxylase deficiency.

Late-onset 21-hydroxylase deficiency (21-OHD) is a congenital enzymatic defect in the glucocorticoid and mineralocorticoid steroidogenic pathways. The manifestations, including hirsutism and infertility, usually occur at puberty or young adulthood. In infertile, anovulatory women with late-onset 21-OHD, the usual therapy is glucocorticoids for ovulation induction. In this case, we report the sole use of clomiphene citrate to induce ovulation in a patient with late-onset 21-OHD. A hirsute and oligomenorrheic woman was diagnosed as having polycystic ovary syndrome at age 25. Her hirsutism responded to oral contraceptives. At age 31, she was given clomiphene citrate alone for ovulation induction and conceived in her fourth cycle. At age 36, because of increased hirsutism she was diagnosed with late-onset 21-OHD by an ACTH stimulation test. The induction of ovulation in late-onset 21-OHD patients has been with glucocorticoids. Given the success in inducing ovulation with clomiphene citrate alone in this patient with well-documented late-onset 21-OHD, it may be worthwhile to study the sole use of clomiphene citrate for ovulation induction in these patients.

17-Hydroxycorticosteroids↗

A preliminary study on the induction of dioestrous ovulation in the mare--a possible method for inducing prolonged luteal phase.

BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. METHODS: In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle > or = 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles > or = 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle > or = 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness.

Animals↗

Ovulation blockade and receptivity in the cyclic rat.

The onset and decline of sexual receptivity was determined around oestrus in intact 5-day cyclic rats and in animals in which spontaneous ovulation was inhibited with nembutal. It was observed that early receptivity (before the critical hours at 14--16 h) could be induced by prior exposure of pro-oestrous females to male rats during the morning at pro-oestrus. In most cases early receptivity was associated with a failure to block ovulation with nembutal administered at 14 h. In cyclic rats receptivity disappeared on the day of oestrus between 8 and 10 a.m. By contrast the period of receptivity was prolonged for 24 h in animals in which ovulation was inhibited by nembutal. Reflex ovulation could be induced by exposure of nembutal-blocked rats to intact as well as to pudendectomized male rats, which latter cannot achieve intromissions. This illustrates the limited role of female genital stimuli in the induction of reflex ovulation. Progesterone (1.25 or 5 mg) injected at pro-oestrus during nembutal sedation did not have an attenuating effect on receptivity 24 h later. It is concluded that LH-surge dependent progesterone secretion at pro-oestrus is not essential for the induction and termination of receptivity around oestrus and that hormones, presumably oestrogens, secreted by the persistent pre-ovulatory follicles, are responsible for the prolonged period of receptivity following nembutal blockade of ovulation.

Animals↗

Observations on the induction of ovulation and expulsion of uterine eggs in the mink, Mustela vison.

In 8 of 12 mink paired for the first time, pairing alone induced ovulation and a short (5 min) interrupted mating led to 8/8 ovulating with normal numbers of corpora lutea. However, in already mated mink, a short mating (Day 7) failed completely or partly (reduced number of ovulations) to induce ovulation. In mink which refused to mate, hCG consistently induced ovulation. In already mated mink (Day 0) a later mating (Day 7), even if interrupted after 5 min, led to expulsion of the first set of eggs, approximately 50% of which were 'lost' by Day 4 and virtually 100% by Day 6. This effect was not produced by pairing without intromission or by treatment with hCG to induce ovulation. It is concluded that copulation is primarily responsible for the loss of eggs from the uterus, although the exact mechanism remains obscure.

Animals↗

Ovulation in the marmoset monkey: endocrinology, prediction and detection.

Circulating progesterone, oestrogens and LH were measured in female marmosets (Callithrix jacchus) over the periovulatory period. Progesterone concentrations increased in all animals within 1 day of the estimated day of ovulation, confirming the usefulness of this hormone for retrospective detection of ovulation. Oestradiol-17 beta and LH both showed a preovulatory rise, but due to the large quantity of plasma required (oestradiol: 0.2 ml) and the length of time taken for the assay (LH: 2-3 days), measurement of these hormones is not practical for the prediction of ovulation. There were no preovulatory changes in unconjugated oestrone, but a rise in total (i.e. conjugated plus unconjugated) oestrone was used to time the collection of recently ovulated oocytes. Levels of oestrone-3-sulphate showed an increase at least 1 day before the expected day of ovulation in four out of five animals. This preovulatory rise can be measured easily by a rapid direct assay, thereby providing a practical method for predicting ovulation in this species.

Animals↗

Potential of aromatase inhibitors for ovulation and superovulation induction in infertile women.

For almost half a century, the first-line treatment for ovulation induction in cases of anovulation, unexplained infertility, or mild male factor has been clomifene (clomiphene citrate). Clomifene is an effective and safely used oral agent, but is known to have relatively common antiestrogenic endometrial and cervical mucous adverse effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancies with clomifene compared with natural cycles. These drawbacks are mainly a result of the extended antiestrogenic effect of clomifene as a result of its accumulation in the body (clomifene isomers have a half-life of several days up to few weeks). Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of clomifene. Over the last few years several published studies, both controlled and noncontrolled, compared clomifene and treatment with aromatase inhibitors (AIs), either alone or in combination with gonadotropins, for ovulation induction or augmentation. These studies found AIs as effective as clomifene in inducing ovulation, with the major advantage of absence of any antiestrogenic adverse effects. Several other major advantages of AIs include the lower serum estrogen production per developing follicle resulting in more physiological estrogen levels around the time of ovulation and good pregnancy rates with a lower incidence of multiple pregnancy than with clomifene. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of gonadotropins required for optimal follicle recruitment and improve the response to gonadotropin stimulation in poor responders. Such preliminary evidence suggests that AIs may replace clomifene in the future because of similar efficacy with a reduced adverse-effect profile. However, we believe that definitive studies in the form of randomised controlled trials comparing clomifene with AIs are needed.

Anovulation↗

Effect of various doses of a gonadotropin-releasing hormone analogue on induction of ovulation in anestrous mares.

One hundred anestrous mares (early February) were injected s.c. with implants containing 0, .9, 1.8, 3.6, or 5.4 mg of a GnRH analogue (goserelin acetate) in an attempt to induce ovarian cyclicity. Follicular activity and concentrations of progesterone and LH were determined every 3 d, or daily during estrus. In treated mares that ovulated, the interval to the second ovulation of the season was compared to that for an additional group receiving 16 h/d of light beginning December 16 (positive controls). Of the mares that did not ovulate in 30 d, eight from each dose group were challenged on d 33 or 34 with an i.v. bolus of 950 micrograms of GnRH. Blood collected at -2, -1, and 0 h before GnRH and at 15, 30, 45, 60, and 90 min and 2, 3, and 4 h after injection was assayed for serum LH. More mares (P < .05) ovulated when given 3.6- (n = 7) or 5.4-mg (n = 6) implants than when given .9-mg implants (n = 0) or placebo (n = 0). Mares with initial follicles < or = 15 mm in diameter were less (P < .05) likely to ovulate (10 of 88) than were those with follicles 16 to 20 mm in diameter (5 of 12). Area under the curve (AUC) for LH was greater for mares receiving larger doses of GnRH. The AUC and peak LH were similar between ovulating and nonovulating mares. Luteinizing hormone peaked in all mares on approximately d 12. There was no difference (P > .05) in either peak LH or AUC among treatment groups in response to the GnRH challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗

Influence of corpus luteum and induced ovulation on ovarian follicular dynamics in postpartum cyclic cows treated with buserelin and cloprostenol.

The influence of the corpus luteum (CL) at the time of buserelin treatment and of buserelin-induced ovulation on the dynamics of ovarian follicular development was determined in 18 postpartum cyclic beef cows injected i.m. with 8 micrograms of buserelin on d 0 (d of treatment) and with 500 micrograms of cloprostenol (PGF) 6 d later. From d 0 to onset of estrus, ovaries were examined ultrasonographically, and blood samples were collected daily. Number of medium (5 to 10 mm) follicles and diameters of the two largest (F1 and F2) follicles in each cow were recorded. Cows were grouped according to the presence (CL+) or absence (CL-) of an active CL before buserelin injection and the presence (OV+) or absence (OV-) of a buserelin-induced ovulation (OV). Three groups were formed: CL-OV+ (n = 8), CL+OV+ (n = 6), and CL+OV- (n = 4). Buserelin induced an ovulation in all CL- cows (progesterone [P4] < .3 ng/mL) and in CL+ cows that had P4 < 4 ng/mL but did not in CL+ cows that had P4 > 8 ng/mL. Within CL+ cows, buserelin-induced ovulation (OV+) was associated with a smaller (P < .0001) increase in F1 and F1-F2 diameters and a transient increase in the number of medium follicles that was greater (P < .03) and of a longer duration (P < .01) than in OV- cows. After PGF, the increase in F1 and F1-F2 diameters was still greater in OV+ than in OV- cows (day x OV; P < .05). In all cows, the selection of the preovulatory follicle occurred before PGF injection. Results indicate that a buserelin-induced ovulation was dependent on P4 concentrations at the time of treatment. Subsequently, ovarian follicular dynamics were altered by a GnRH-induced ovulation, but emergence and selection of a large growing follicle occurred in all cows within 6 d of treatment. This follicle became the preovulatory follicle following PGF-induced luteolysis.

Animals↗

Porcine follicle-stimulating hormone treatment of gilts during an altrenogest-synchronized follicular phase: effects on follicle growth, hormone secretion, ovulation, and fertilization.

Porcine FSH (SUPER OV), containing .03% LH activity, and equine chorionic gonadotropin (eCG) were administered during an altrenogest-synchronized follicular phase to determine their effects on follicle development, estrus, ovulation, and fertilization. Treatments were made by i.m. injection starting on d 1 (24 h after the last feeding of altrenogest): 1) saline, once, n = 14; 2) eCG (1,200 to 1,500 IU) once, n = 32; 3) FSH 14 (n = 2) or 21 (n = 6) NIH-FSH-S1 units/100 kg BW, divided among six injections at 12-h intervals (FSH14/21); 4) FSH, 28 NIH-FSH-S1 units/100 kg BW, divided among six injections at 12-h intervals, n = 12; and 5) FSH, 28 NIH-FSH-S1 units/100 kg BW and 100 IU hCG, two or six injections at 12-h intervals (FSH28+hCG), n = 13. Gilts were injected with 750 IU of hCG on d 5 to ensure ovulation. Twenty-eight eCG- and FSH-injected gilts (n = 6, 8, and 11 on treatments 3, 4, and 5, respectively) were bred and laparotomized on d 7 to recover ova and record ovulation rate. The mean number of ovulations and large (6- to 10-mm) follicles, respectively, on d 7 were as follows: saline (17, .7), eCG (43, .9), FSH14/21 (15, .6), FSH28 (12, 16), and FSH28+hCG (32, 21). Plasma FSH concentrations were at least threefold higher (P < .05) in gilts treated with FSH than in gilts not treated with FSH. The percentage in estrus was higher (P < .05) for saline- and eCG-treated gilts (100 and 87%, respectively) than for FSH-treated gilts (53%). Proportion of FSH28+hCG-treated gilts with fertilized ova (27%) was lower than for other groups (79 to 100%). In summary, the 3-d high dose FSH treatment (FSH28 and FSH28+hCG) during an altrenogest-synchronized follicular phase increased the number of potentially ovulatory follicles, but this potential benefit was not realized because many follicles failed to ovulate. The co-injection of low doses of hCG (FSH28+hCG) increased the ovulation rate and estradiol secretion but reduced ova recovery and fertilization rate compared with eCG and the other FSH treatments.

Analysis of Variance↗

Induction of ovulation with clomiphene citrate in combination with metoclopramide in patients with amenorrhea of hypothalamic origin.

Literature data have demonstrated that the chronic use of metoclopramide (MCP), a dopamine antagonist, causes increased gonadotropin secretion in patients with hypothalamic amenorrhea but without triggering ovulation. It has also been observed that women with hypothalamic amenorrhea respond poorly to ovulation induction with clomiphene citrate (CC). On this basis, the objective of the present study was to determine the effect of MCP on the response to CC in patients with hypothalamic amenorrhea in order to evaluate the validity of the simultaneous use of these drugs as ovulation inducers in this type of chronic anovulation. Twenty-two patients with amenorrhea of hypothalamic origin were submitted to a randomized double blind study in which one tablet of 5 mg MCP or placebo was administered every 8 hours for 2 months. After the 30th day of medication (MCP or placebo), CC, 100 mg orally, was additionally administered to both groups for 5 days. Blood samples were collected on days 1, 15 and 30 during the first month of the study and on days 7, 14 and 21 after the last CC tablet during the second month, for later measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol and progesterone by radioimmunoassay. The group that received MCP showed a significant increase in LH and FSH during the first month of the study, as well as a slighter increase in estradiol. Prolactin increased only during the second stage of treatment. No significant increases in gonadotropins, prolactin or estradiol occurred in the placebo group. In the group treated with MCP, 40% of the patients ovulated after CC, with menstruation occurring in 60% of them. In the placebo group, 33.3% of the women ovulated after CC and 44.4% menstruated at the end of the study. We conclude that MCP increases the circulating levels of LH, FSH, estradiol and prolactin in patients with hypothalamic amenorrhea and low estrogen levels, supporting the hypothesis that an increase in hypothalamic dopaminergic tonus occurs in these patients. On the other hand, the combination of MCP and CC does not improve the rate of ovulation compared to placebo.

Adult↗

Natural family planning. I. The peak symptom and estimated time of ovulation.

The observation of the "Peak" mucus symptom in women using the ovulation method of natural family planning has been correlated with the estimated time of ovulation, as evaluated by indirect hormonal parameters. In 65 cycles of the 73 studied in 24 patients, there was hormonal confirmation of ovulation; in eight cycles, anovulation or luteal dysfunction was suspected. In the 65 normal cycles, 64 exhibited a Peak symptom. In those cycles, ovulation was estimated to occur from 3 days before to 3 days after the Peak symptom with a mean of 0.31 days before the Peak symptom. In 95.4% of these cycles, ovulation was estimated to occur from 2 days before to 2 days after the Peak symptom. The variation between cycles of the same patient ranged from 0 to 4 days with a mean of 1.8 days. The beginning of the mucus symptom preceded the estimated time of ovulation by an average of 5.9 days.

Adult↗

Induction of ovulation by clomiphene citrate in the Indian vespertilionid bat, Scotophilus heathi.

The ovulation induction property of clomiphene citrate (CC) and human chorionic gonadotropin (hCG) was studied in Scotophilius heathi, an Indian tropical vespertilionid bat, during the period of delayed ovulation between December to early January. The results of the study showed that 10 microg of CC alone was ineffective to induce ovulation, whereas 100 microg CC and 10 IU hCG alone induced ovulation. A significant (P < 0.01) increase in the ovulation rate was observed when 10 microg CC followed by 10 IU hCG, compared to 10 IU hCG and 100 microg CC alone groups. Finally, CC at a 100 microg dose, followed by 10 IU hCG, produced superovulation (14.00 +/- 0. 70), which is significantly different in comparison to all other groups. This is the first report of ovulation induced by CC in the Indian tropical bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary syndrome (PCOD) during the normal physiology of reproduction.

Animals↗

Recombinant FSH versus urinary gonadotrophins or recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: Over the last four decades, various urinary FSH (uFSH) products of different purity have been developed. In 1988 recombinant FSH (rFSH ) was prepared by transfecting Chinese hamster ovary cell lines with both FSH subunit genes. Both rFSH and uFSH are known to be effective in inducing ovulation in women with clomiphene-resistant polycystic ovary syndrome. Ovulation induction with FSH bears the risk of multiple follicle development, multiple pregnancies and ovarian hyperstimulation syndrome. The dose regimen used can affect the incidence of these complications. OBJECTIVES: To compare in women with clomiphene-resistant polycystic ovary syndrome (PCOS) the safety and effectiveness in terms of ovulation, pregnancy, miscarriage, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) of 1) rFSH with uFSH and 2) different dose regimens of rFSH. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. SELECTION CRITERIA: All relevant published RCT's were selected. Randomised controlled trials were eligible for inclusion if treatment consisted of recombinant FSH versus urinary FSH or recombinant FSH in different dose regimens, to induce ovulation in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. Handsearching of bibliographies of relevant publications and reviews and abstracts of scientific meetings was performed. Serono Benelux BV and NV Organon, the manufacturers of follitropin alpha (Gonal F(R)) and follitropin beta (Puregon(R)) respectively, were asked for unpublished data and ongoing studies. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed according to predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Four randomised trials comparing rFSH versus uFSH were identified. No significant differences were demonstrated for the relevant outcomes. The odds ratio for ovulation rate was 1.19 (95% CI 0.78,1.80), for pregnancy rate 0.95 (95% CI 0.64,1.41), for miscarriage rate 1.26 (95% CI 0.59,2.70), for multiple pregnancy rate 0.44 (95% CI 0.16,1.21) and for OHSS 1.55 (95% CI 0.50,4.84). Similarly, in the only randomised trial that compared chronic low dose versus conventional regimen with rFSH no significant differences were found. REVIEWER'S CONCLUSIONS: At this moment there are not sufficient data to determine which of rFSH or uFSH is preferable for ovulation induction in women with PCOS.

Clomiphene↗

Partial denervation of the ovaries by transection of the suspensory ligament does not inhibit ovulation in rats treated with pregnant mare serum gonadotropin.

Adrenergic nerves reach the ovary via two routes: along the arteries to the ovary and via the suspensory ligament. Results from earlier investigations suggest that denervation of the nerves along the arteries does not influence the ovulatory process. In the present study we have examined whether denervation by transection of the ovarian suspensory ligament influences the ovulatory process. Partial denervation of the ovary by transection of the ovarian suspensory ligament, sham operation, or only anesthesia were performed on immature 25-day-old rats. To induce ovulation, pregnant mare serum gonadotropin (PMSG) was injected in the morning (0800-0930), when the rats were 26 days old. This PMSG treatment normally induces ovulation around 0200 in the early morning of day 29 with subsequent formation of corpora lutea. Rats were killed 5-8 hr, 3 days, and 5 days after this ovulation time. Ovarian interstitial norepinephrine levels were markedly decreased after transection of the suspensory ligament. Ovulations had occurred in all denervated, as well as sham-operated, and control rats. The various groups did not differ in the number of ovulations per rat. Thus, the adrenergic nerves in the suspensory ligament appear not to be necessary for ovulation. Whether catecholamines themselves play a role in the ovulatory process cannot be elucidated from this experiment, since the norepinephrine content in the ovary was not totally depleted. It seems unlikely that adrenergic nerves reach the corpus luteum via the suspensory ligament, since transection of this structure did not change the luteal content of norepinephrine.

Animals↗

An intrabursal injection procedure for the in vivo study of ovulation in hamsters.

A new procedure for studying the effect of various drugs on ovulation in vivo is described. In golden hamsters (Mesocricetus auratus), each ovary is enclosed within a complete bursa that is continuous with the oviduct. Drugs can be applied topically to ovaries by injection of a solution into a bursal cavity of an anesthetized hamster several hours before ovulation; the contralateral ovary serves as an in vivo control and receives no treatment. After ovulation, the number of ruptured follicles on experimental and control ovaries are compared. Data presented show that: (1) the operation and injection procedure per se do not affect ovulation; (2) normal saline is a suitable vehicle for administration of drugs by this route; (3) compounds with molecular weights of less than 1,000 daltons rapidly penetrate all layers of the follicle wall; (4) solutions injected into the bursal cavity 6 hours before ovulation remain there until ovulation. The advantages and limitations of this technique are discussed.

Animals↗

Drugs that block smooth muscle contraction inhibit in vivo ovulation in hamsters.

We have demonstrated previously that smooth muscle cells (SMC) in the base of hamster follicles contract minutes before ovulation. The contraction of these cells correlates well in time with the development of a constriction in the base of the follicle. The purpose of this study was to determine whether contraction of SMC (1) produces this constriction and (2) is necessary for ovulation. We treated preovulatory hamster ovaries with six classes of drugs (lanthanides, calcium antagonists, local anesthetics, prostaglandins, cAMP modulators, and cytochalasin B) known to inhibit SMC contraction in other tissues. Drugs were injected into the experimental bursal cavity of a hamster 3 hours before ovulation; the contralateral ovary received no treatment and served as a control. Three hours after ovulation, the number of ruptured follicles on experimental and control ovaries were compared by light and electron microscopy. All the smooth muscle (SM) inhibitors, except those that affect cAMP levels and cytochalasin B, prevented (1) contraction of follicular SM, (2) constriction of the base of the follicle, and (3) ovulation. These results support the idea that contraction of follicular SMC constricts the follicle and is required for ovulation. The results further show that follicular SMC are activated by an influx of extracellular calcium and that prostaglandin F2 alpha may be involved in promoting this contraction.

Animals↗

Effects of pH on in vitro ovulation of goldfish (Carassius auratus) oocytes.

The in vitro effects of pH on goldfish (Carassius auratus) ovulation were investigated. Final oocyte maturation and follicular detachment were induced in vivo in gravid goldfish by HCG injections and elevated holding temperatures. Females were biopsied to determine the time of germinal vesicle breakdown and when oocytes should be removed for in vitro incubations. Prior to ovulation, the ovaries were removed, dissected and mature intrafollicular oocytes were incubated in media of varying pH (7.3-8.9). There was a significant increase in ovulation as the pH of the incubation increased and this ovulation could be blocked by indomethacin. Indomethacin did not inhibit the actual mechanism of oocyte expulsion since exogenous PGF2 alpha induced ovulation in indomethacin blocked incubates. Increased pH did not increase the ovulatory response observed with exogenous PGF2 alpha. The combined results suggest that an increase in incubation pH stimulates prostaglandin synthesis that, in turn, stimulates ovulation.

Animals↗