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In the course of investigations on the frequency of fertilization in immature rats which had been caused to ovulate by the injection of gonadotrophins, it was observed that a remarkably large number of eggs from unmated rats had divided so as to simulate segmentation very closely. Fragmentation resembling segmentation in tubal as well as ovarian eggs is a well-known phenomenon, but there is little specific information on the frequency with which it occurs.
Kampmeier [1929], who reviewed the early literature, stated that it was first reported by Pflüger in 1863 in ovarian eggs. Numerous papers have since appeared giving details of nuclear and meiotic changes observed. Kingery [1914] studied the eggs in atretic follicles of immature mice and found abnormal maturation spindles but no segmentation spindles. He frequently observed eggs with several or numerous 'cells', but these contained abnormal, several, or no nuclei. Loeb [1932] reported the finding of embryonal
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Abstract
The effects of a single injection of recombinant human FSH (rhFSH; Org32489) on ovulation rate and timing and on antral follicle growth were studied in adult 5-day cyclic rats. Rats injected at 1700 h on dioestrus-2 with a dose of 10 IU rhFSH showed, on average, no increase in ovulation rate on the day of expected oestrus. However, an additional, precocious ovulation resulting in a normal number of corpora lutea 13·3±0·4, n=6) was found to take place on the night after injection, i.e. dioestrus-3. No mating behaviour, as shown by the absence of vaginal plugs the next morning, was observed at this ovulation. Follicle counts showed a loss of large antral follicles due to ovulation and increased numbers of healthy small antral follicles at 17 and 41 h after injection, indicating a decrease of atresia of growing follicles as well as additional recruitment of new antral follicles. The endogenous serum FSH concentration on the subsequent day of oestrus (65 h after the rhFSH injection) as well as recruitment of small antral follicles were lower in the rhFSH-treated rats than in saline-treated controls. The ovulation at oestrus, 48 h after the precocious, rhFSH-induced ovulation showed large differences in the number of oocytes between the rats in one treatment group.
Similar results in terms of immediate ovulation induction were obtained by using a highly purified human urinary FSH preparation (i.e. metrodin). Furthermore, the direct induction of ovulation by rhFSH or metrodin could not be prevented by the injection of an LHRH antagonist.
It was concluded that rhFSH can induce acute ovulation in rats, and stimulates follicular development directly or indirectly through increased FSH levels after ovulation. It induces antral follicle growth and decreases early atresia in small antral follicles.
Journal of Endocrinology (1995) 144, 39–47
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Urine for the analysis of pregnanediol was collected weekly for 3 months from 209 menstruant women aged 11–24 years who lived with their parents and from 59 women aged 17–23 years who had left the parental home. Menstrual cycles were classed as ovulatory if the 24-h pregnanediol output in the 12 days preceding menstruation was ≥ 5 μmol on a single occasion or if the total excreted on 2 days, 1 week apart, was ≥ 7 μmol.
In the first group, ovulatory incidence increased with menarchal age. Unfailing ovulation occurred in 22·9, 25·0,44·8,42·9, 63·2, 71·8 and 82·6% of those who were < 1, 1−<2, 2−<3, 3−<4, 4−< 5, 5–8 and 9–12 years from menarche. Comparable figures for the women who lived in flats and hostels were 40·0% (menarchal age, 5–8 years) and 78·6% (9–12 years).
It is concluded that a regular pattern of ovulatory menstrual cycles is established in most young women within 5 years of the menarche, and that departure from the family home is often associated with a regression to a juvenile pattern of anovulatory menstrual cycles.
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SUMMARY
Immature mice were induced to ovulate by a single injection of pregnant mare serum gonadotrophin (PMS). Additional treatment with 5-hydroxytryptamine (5-HT) during the final 24 hr. of the experiment caused significant alteration in the dose-response relationship for PMS, the ovulatory response to low doses of PMS being increased and that to high doses reduced. Both lysergic acid diethylamide and methysergide caused a consistent and significant reduction in the incidence of ovulation induced under the same test conditions.
Neither 5-HT nor its antagonists influenced spontaneous ovulation in adult mice of a different strain under the conditions tested. Therefore, if 5-HT is involved at some stage in the processes leading up to ovulation when this is induced in immature mice, either it does not have the same importance or its effect is less easily modified under the physiological conditions of spontaneous ovulation in mice of the strain used.
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SUMMARY
Ovulation was induced in immature mice by pregnant mare serum gonadotrophin. Reserpine in doses of 6–9 μg. prevented ovulation in these animals. Methoserpidine (up to 333 μg.) did not reduce the incidence of ovulation. A single dose of 2 mg. α-methyldopa was without effect but several doses at intervals inhibited ovulation.
Groups of mice treated with gonadotrophin and reserpine were pretreated with other drugs. α-Methyldopa decreased the sedative effect of reserpine but not its inhibitory effect on ovulation. Dopa antagonized both effects of reserpine.
5-Hydroxytryptamine creatinine sulphate in doses of 100 or 200 μg. injected s.c. 16 or 17 hr. before the mice were killed consistently increased the percentage ovulating in response to gonadotrophin. A significant increase was also obtained when 5-hydroxytryptophan was injected into mice pretreated with iproniazid.
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SUMMARY
When oestrogen was administered early in the oestrous cycle of the rat on the day of metoestrus, the inhibitory effect of progesterone injected at dioestrus on ovulation was lost and a facilitatory effect was observed; ovulation was advanced by one day. The advancement of ovulation by oestrogen injected at the dioestrus — 1 stage of a 5-day cycle was confirmed; it was shown that this response could be elicited by as little as 0·13 μg. oestradiol benzoate. These results are discussed in relation to other studies on the time of oestrogen secretion in the normal cycle, the alteration of the response of the pituitary to progesterone injection from an inhibitory to a facilitatory effect by previous exposure to oestrogen, and the mechanism of induction of ovulation by oestrogen in the 5-day cycle and in pregnancy. The relevance of these and similar experiments on the induction of ovulation by ovarian steroids in the rat as a guide to what is occurring during the normal cycle is questioned, principally because when ovulation was induced by these means the changes in the activity of the thyroid gland that are associated with ovulation in the normal cycle were not reproduced.
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SUMMARY
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.
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SUMMARY
Luteinizing hormone, FSH, prolactin, oestradiol and progesterone concentrations were measured by radioimmunoassay in the blood of female rats from 7 days before the first ovulation (the day of first ovulation is designated day 0) until the day after the second ovulation. Serum LH concentrations varied between 29 and 59 ng NIAMDD-rat-LH RP-1/ml from days −7 to −2. On the day preceding first ovulation (day − 1) a steep increase in serum LH was found between 13.00 h and 15.00 h reaching a maximal value of 2100 ng/ml at 17.00 h. Thereafter LH levels decreased to undetectable values (< 15 ng/ml). Serum FSH concentrations from days −7 to −2 varied between 108–154 ng NIAMDD-rat-FSH RP-1/ml; increased concentrations were found on the afternoon of day − 1 and on the morning thereafter (first oestrus) with a maximal value of 1150 ng/ml at 19.00 h on day − 1. On the day preceding the second ovulation (day +4) LH and FSH peaks were again found.
Prolactin concentrations on the days preceding first ovulation were generally low. A small rise was found nearing first ovulation (12·7 ng/ml, day −6; 23·9 ng/ml, day −2). On day − 1 a peak (118 ng/ml) was found at 15.00 h, similar to that found on day +4 in adult pro-oestrous rats.
Plasma progesterone concentrations also reached a peak value (50 ng/ml) on day − 1, at 17.00 h, preceded by concentrations between 3–5 ng/ml from days −6 to −2. Progesterone concentrations after the first ovulation showed a pattern characteristic of the adult cycle.
Plasma oestradiol levels were undetectable (< 10 pg/ml) from days −6 to −2; a clearly increased oestradiol concentration was found on day −1, reaching a value of 98 pg/ml. One and two days before the second ovulation, oestradiol levels rose again.
The differences and similarities between pubertal and adult pro-oestrous hormone peaks are discussed.
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SUMMARY
Electrical stimulation of the anterior hypothalamus (regions of the supraoptic and anterior hypothalamic nuclei) or of the ventro-medial hypothalamus (infundibular or ventro-medial nuclei) during the last month of anoestrus in ewes induced ovulation within 72 hr., while similar stimulation of the same centres during the breeding season on the 12th day of the oestrous cycle did not advance ovulation. The role of the hypothalamic centres in the control of gonadotrophin secretion and ovulation is discussed in the light of these results.
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In some animals which ovulate spontaneously, oestrogen may stimulate prolactin secretion and high levels of prolactin may inhibit steroid-induced surges of LH. The possibility was investigated that such conditions were operating in the reflex ovulator Microtus agrestis to prevent spontaneous ovulation. However, bromocriptine treatment to suppress prolactin secretion did not enhance the poor ovulatory response to administration of oestradiol benzoate.
