Ovarian response to hCG injections during the prepubertal period in three breeds of sheep with different ovulation rates and litter sizes

A positive correlation was reported between ovulation (OR) rate in response to hCG in prepubertal ewe lambs and adult ewes. The finding suggested that the response to hCG may be used to select prepubertal ewe lambs for prolificacy. We studied plasma FSH concentrations and ovarian response to hCG injection during the prepubertal period in breeds with high (Chios), medium (Florina) and low (Karagouniki) OR and litter sizes (LS). The results showed that Chios ewe lambs presented a higher profile of plasma FSH during the 3rd to 7th wk of age when compared to the breeds with medium (Florina) and low (Karagouniki) OR and LS. The ovarian response to hCG showed that the Chios ewe lambs responded earlier, by exhibiting ovulation at 6 wks and more effectively, by demonstrating a higher OR than the other two breeds. There was no correlation among plasma FSH concentrations during prepubertal age (3rd to 7th wk), ovulation rate after hCG injection, or litter size at first and second lambing for all breeds. Therefore we concluded that the plasma FSH concentrations and/or the ovarian response to hCG injection during the prepubertal period is not a suitable criterion for early selection for litter size in the adult ewe of these breeds.     

Induction of ovulation and oocyte maturation of amphibian (Rana dybowskii) ovarian follicles by protein kinase C activation in vitro.

We previously reported that protein kinase C (PKC) activation induced meiotic maturation (germinal vesicle breakdown, GVBD) of Rana dybowskii follicular oocytes cultured in vitro without hormone treatment. The experiments reported here were carried out to establish whether ovarian follicles ovulated in response to PKC activation during culture. A phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was used for PKC activation. TPA addition (10 microM) to cultured ovarian fragments induced ovulation and maturation of the oocytes similar to that seen following addition of frog pituitary homogenate (FPH, 0.05 pituitary/ml) or progesterone (0.5 microgram/ml). Such changes were not observed when ovarian fragments were treated with inactive phorbol ester. The time course of TPA-induced ovulation was similar to that produced by FPH-stimulated ovulation. Both TPA- and FPH-stimulated ovulation and maturation were blocked by treatment with cycloheximide, forskolin (an adenylate cyclase stimulator), and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7; a PKC inactivator). FPH treatment markedly increased progesterone levels in the medium during ovarian fragment culture whereas TPA treatment failed to elevate progesterone levels. Thus, TPA treatment mimics FPH and progesterone in inducing ovulation and meiotic maturation in cultured amphibian ovarian fragments. The data strongly suggest that PKC plays an important role in regulating ovulation as well as in modulating amphibian oocyte maturation during follicular differentiation.     

促性腺激素诱导猕猴排卵周期中卵巢纤溶酶...

Changes of plasminogen activator (PA) and its inhibitor (PAI-1) activity and antigen have been investigated during PMSG/hCG induced ovulation in rhesus monkeys. It has been demonstrated that the ovarian tissue type PA (tPA) activity, which reaches maximum prior to ovulation and declines thereafter, is closely related to follicular rupture; significant increases in urokinase type PA (uPA) only occurs in granulosa cells after ovulation. Since the secretory activity of ovarian PAI-1 reaches its peak level 12-24 h earlier than tPA the rapid decrease in PAI-1 activity in the approach of ovulation is correlated with the elevation of tPA activity. It is, therefore, suggested that a counterbalance of tPA and PAI-1 activity within the ovary may play an important role in the ovulation mechanism, whereas uPA may be involved in the regulation of corpus luteum formation.     

Serotoninergic mechanisms in ovarian cycle (author's transl)]

Influence of 5-HT on the rat follicle rupture mechanism was studied by the administration of p-clorophenyl-alanine (p-CPA) (300 mg/kg) at different stages of the ovarian cycle. The ovarian cycle of treated rats was subject of investigation, as well as the histology of tubes and ovaries. Administration of p-CPA at 10 hours of metestrus phase induces an inhibition of ovulation. Predominant diestrus phases in the ovarian cycle and luteinitation of ovaries suggested an increase in progesterone secretion probably owed to a correspondingly greater prolactine secretion. Adequate 5-HT levels in central structures proved to necessary for normal ovulation.     

Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials

Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.     

Inhibitory effect of glucocorticoid and stimulatory effect of human chorionic gonadotropin on ovarian carbonyl reductase in rats.

Effects of three glucocorticoids on ovulation, and on content and activity of ovarian carbonyl reductase in rats were investigated. Glucocorticoid treatment caused both significant decrease in ovarian and uterine weights, blockade of ovulation and marked decrease in content and activity of ovarian carbonyl reductase. Furthermore, the weak immunoreactivity to antibody against ovarian carbonyl reductase was shown in the theca cells and the interstitial gland cells in the glucocorticoid-treated ovary. The treatment with hCG (LH activity specific) restored the ovarian weight, and both the content and activity of ovarian carbonyl reductase, which were inhibited by glucocorticoids, to control level as well as ovulation. These results indicate that the ovarian carbonyl reductase may be closely involved in ovarian function, especially ovulation, and may be an LH-dependent enzyme, because it is well known that glucocorticoids inhibit both LH surge and ovulation in rats.     

Influence of mating on ovarian follicle development in Triatoma infestans (Klug, 1834).

This work examines the influence of mating on ovarian follicle development in Triatoma infestans. The observations were carried out on both virgin and mated females, which were killed at various times after their emergence. There was no difference in the ovarian development of both experimental groups during the first gonadotrophic cycle. By the 7th day mated females as well as virgin females showed vitellogenic oocytes. The coriogenesis and ovulation process began on the 13th day after imaginal moulting. However we could observe that egg-laying was dependent on mating. Mated females laid eggs whereas virgin females did not lay eggs. However ovarian production was significantly greater in the mated females. It is suggested that in T. infestans mating stimulates egg-laying but it does no influence the oogenesis and ovulation process.     

Ovulatory patterns in the squirrel monkey (Saimiri sciureus)

The results of induced ovulation regimens on 95 squirrel monkeys (Saimiri sciureus) over a 7-year period are described. A distinct seasonal pattern of response was observed in the temperate climate.The pretreatment of squirrel monkeys with progesterone slightly suppresses the total number of follicles showing growth in response to the FSH but results in a significantly higher number of animals showing at least one ovulation.No significant differences were noted for ovarian response based on the length of time the animal had been in captivity.The effectiveness of the ovulation induction regimen over 20 or more consecutive courses of treatment was not significantly reduced, suggesting that antibodies were not formed against the gonadotropins.     

Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian surface epithelium

The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17beta-estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and (3)H-thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury- or ovulation-induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation-associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations.     

The effects of powdered carp pituitary on ovarian development, ovarian ascorbic acid and ovulation in Carassius carassius L. exposed to various photoperiod and temperature regimes

The effects of temperature, photoperiod and powdered carp pituitary on ovarian development (measured by change in diameter of intraovarian eggs and gonadosomatic index), ovulation and ovarian ascorbic acid have been studied in crucian carp in winter. Short photoperiods stimulated ovarian development but long photoperiods were inhibitory. Photoperiod seemed to exert this effect by altering the release of pituitary gonadotropin. Temperature affected ovarian development independently of photoperiod. High temperatures were stimulatory and overcame the negative effect of a long photoperiod. The results suggested that temperature acts at the level of the gonad rather than the pituitary. On the basis of these findings a hypothesis is suggested to explain gonadal cycles in cyprinids and similarities to previous findings in other fish groups are discussed.
Levels of ovarian ascorbic acid varied according to treatments. Ovulation was associated with a decreased level. The results suggested that this vitamin aids biosynthesis of sex steroids in a similar fashion to that observed in higher animals. The results also demonstrated that measurement of gonadal ascorbic acid can provide a useful indication of physiological events at the level of the gonad.     

Ovarian response to PMSG treatment in ewes immunized against oestradiol-17 beta

The effects of active immunization against oestradiol-17 beta on the ovarian response to pregnant mare serum gonadotrophin (PMSG) was investigated in Merino ewes. Immunized (79) and control (41) ewes were synchronized with intravaginal sponges, given either 750 or 1500 i.u. PMSG and then mated to rams or inseminated laparoscopically with fresh diluted semen. All control ewes mated naturally exhibited oestrus and 40 out of 41 control ewes ovulated. The ovulation rate was higher in the controls receiving 1500 i.u. PMSG than in those ewes which received 750 i.u. PMSG (10.2 v. 3.3). Immunization against oestradiol-17 beta resulted in antibody titres varying from 100 to more than 100 000 in plasma taken 1-4 days after mating. The ovarian response increased significantly in the lowest titre group (100-1000) in conjunction with stimulation with 1500 i.u. PMSG. In these ewes the ovulation rate increased over controls (16.7 v. 10.2) as did the total ovarian response, which includes follicles greater than 10 mm diameter (22.3 v. 11.1). The total ovarian response was also increased in those ewes given 750 i.u. PMSG which had titres in the 1000-10 000 and 10 000-100 000 range, but this was not accompanied by significant increases in the ovulation rate. In general, the higher titre levels (greater than 1000) were correlated with decreases in the proportion of ewes showing oestrus and ovulating and in the embryo recovery rate. The 1500 i.u. PMSG treatment group with the highest titres (greater than 10 000) also showed a significant drop in the ovulation rate as compared to the 1500 i.u. PMSG controls.     

Evidence for a role of the ovarian surface epithelium in the ovulatory mechanism of the sheep: secretion of urokinase-type plasminogen activator

The extent of dissolution of tissues within the apical wall of the preovulatory ovine follicle (formative site of rupture) is greater than that of the counterpart basal hemisphere. It has been hypothesized that proteolytic enzymes released from contiguous ovarian surface epithelial cells contribute to apical follicular weakening and ovulation. Ovulation occurs from the dominant ovarian follicle of proestrous ewes at approximately 24 h after administration of luteinizing hormone-releasing hormone (LHRH). Follicular rupture was inhibited in sheep in which the ovarian surface epithelium was surgically removed at 8 (but not at 16) h following LHRH. Plasminogen activator bioactivity was greater within the follicular apex compared to basal wall at 12 h; this difference was negated by prior removal of epithelium at 8 h after LHRH. A low M_r plasminogen activator of the urokinase-type (uPA) was secreted by epithelial cells recovered from the surface of preovulatory follicles (Western blot analysis). Ovarian epithelium, not associated with a preovulatory follicle, produced very little uPA. Finally, ovulation was suppressed by intrafollicular injection (8 h post-LHRH) of uPA antibodies. It is suggested that secretion of uPA by ovarian surface epithelium and consequent plasmin up-regulation within neighboring tunica albuginea and follicular theca is a contributing factor in the mechanism of ovulation.     

Involvement of cytosolic phospholipase A2 in the ovulatory process in gonadotropin-primed immature rats

The preovulatory LH surge induces a remarkable increase in ovarian prostaglandins (PGs) which help to mediate the ovulatory process. We investigated whether cytosolic phospholipase A2 (cPLA2) has a role in this PG production in PMSG/hCG-primed immature rats. The immunoreactive signal for cPLA2 was localized in both thecal and granulosa layers of mature follicles and became evident in response to gonadotropins. The PLA2 activity in the whole ovarian cytosol rose slightly after PMSG stimulation, persisted relatively constant until 24 h after hCG injection and thereafter increased gradually. Intra-ovarian bursal injection of arachidonyl trifluoromethyl ketone, a specific inhibitor for cPLA2 ( 1.0-3.0 mg/ovary), significantly reduced ovarian PGE2 content and the ovulation rate. These results suggest that cPLA2 exists in periovulatory follicles and functions in PG production related to the ovulation process.     

Correlation between steroids and plasmin in rat ovaries during ovulatory process.

Progesterone (0.5 mg/rat) and estradiol-17 beta (10 micrograms/rat) injected(im) to adult female albino rats on the morning of proesterous significantly enhanced the ovarian plasmin activity as measured by the fibrin plate method at the time of ovulation which was confirmed to be at 2.30 a.m. by estimation of ovarian plasmin activity at definite intervals before and after ovulation. The ovarian plasmin activity showed a gradual increase towards ovulation and reached a maximum level at 2.30 a.m. and again decreased after ovulation. However, the nonsteroidal estrogen antagonist, tamoxifen induced inhibitory effects on the ovarian plasmin activity as compared to control and estradiol-17 beta treatment. Thus these studies reveal a positive relationship between steroids and the ovarian plasmin activity during ovulation.     

Veterinary clinical application of GnRH--questions of efficacy

The efficacy of GnRH treatments are reviewed in relation to prevention of embryo mortality, control of follicle development in synchronization programmes using PG as luteolysin, induction of ovulation in post-partum anoestrus and in bovine cystic ovarian disease. It is suggested that in cattle that GnRH is effective in increasing pregnancy rates when given either at the time of insemination (first or repeat) or between days 11 and 14 after insemination. Evidence is also presented for positive effects on pregnancy rates in sheep, mares and sows. Use of GnRH as an integral part of synchronising regimens where it is given 7 days before PG and then again 48-60 h after PG appears to be effective in increasing the synchrony of ovulation in controlled breeding programmes. The main synchronizing effect seems to reside in the second GnRH injection whereas the importance of the first is in prolonging the luteal phase in those cows treated late in the cycle. The published work on the potential use of GnRH to induce ovulation in anovulatory cattle is reviewed. Neither bolus dose injections, pulsatile, continuous infusion, nor controlled release formulations of GnRH, have yet proved effective in inducing fertile ovulations in a predictable or consistent manner. It is suggested that this is due to the variability of follicular status when treatment is initiated. GnRH is commonly used in the treatment of bovine cystic ovarian disease. However, although stimulating ovulation/luteinisation of a new follicle and luteinisation of the cyst, fertility of treated cattle remains very poor and it is suggested that a better understanding of the disease is needed before more effective treatments can be developed.     

Rat ovarian prostaglandin levels and ovulation as indicators of the strength of non-steroidal anti-inflammatory drugs

Immature Wistar rats were treated with pregnant mare's serum gonadotropin and human chorionic gonadotropin to induce ovulation. The non-steroidal anti-inflammatory drugs indomethacin, diclofenac, flurbiprofen, and phenylbutazone inhibited both the ovulation rate and the normal increase in ovarian prostaglandin E during ovulation. Tolmetin, ibuprofen, and aspirin did not have any significant effect. There was a significant correlation between the ovulation rate and the level of ovarian prostaglandin E following treatment with these drugs. When indomethacin was given in graded doses, there was also a correlation between ovulation rate and the dose-dependent inhibition of ovarian prostaglandin E.     

Bovine model of reproductive aging: response to ovarian synchronization and superstimulation

The responsiveness of the hypothalamo-pituitary axis to steroid treatments for ovarian synchronization and the ovarian superstimulatory response to exogenous FSH was compared in 13-14 year old cows and their 1-4 year old young daughters. We tested the hypotheses that aging in cattle is associated with: (1) decreased follicular wave synchrony after estradiol and progesterone treatment; (2) delayed LH surge and ovulation in response to exogenous preovulatory estradiol treatment; (3) reduced superstimulatory response to exogenous FSH. Higher plasma FSH concentrations (P<0.01), and a tendency (P=0.07) for fewer 4-5 mm follicles at wave emergence were observed in old cows (n=10) than in young cows (n=9). The suppressive effect of estradiol/progesterone treatment on FSH was similar between old and young cows. Although the preovulatory LH surge in response to estradiol treatment was delayed in old than young cows (P=0.01), detected ovulation times were not different. No difference in ovarian superstimulatory response was detected between age groups, but old cows (n=8) tended (P=0.10) to have fewer large follicles (>or=9 mm) 12 h after last FSH treatment than in young cows (n=7). We concluded that pituitary and ovarian responsiveness to estradiol/progesterone synchronization treatment was similar between old and young cows, but aging was associated with a delayed preovulatory LH surge subsequent to estradiol treatment. Old cows tended to have fewer large follicles after superstimulatory treatment than young cows.     

Effect of selective removal of the adrenal medulla on female sexual development

The ovary and adenohypophysis of the rat contain beta-adrenergic receptors and respond to beta-adrenergic stimulation with hormone release. To determine the importance of the adrenal medulla as a source of adrenergic influences regulating prepubertal ovarian and pituitary function, a technique was developed to remove most of the adrenal medulla without compromising adrenocortical function. Medullectomy (MED) of 24-day-old female rats depressed both spontaneous diurnal changes in plasma epinephrine (EPI), and the EPI and norepinephrine (NE) response to decapitation, without affecting corticosterone (B) levels. Vaginal opening and first ovulation were delayed in MED rats. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were normal in MED rats, but those of growth hormone (GH) and prolactin (Prl) were depressed. MED reduced the ovarian weight response to pregnant mare's serum gonadotropin (PMSG) and the ovarian steroidal response to human chorionic gonadotropin (hCG) in vitro, but it did not affect ovarian beta-adrenergic receptors. Cultured granulosa cells, harvested from juvenile ovaries and primed in vitro with FSH, responded to nanomolar concentrations of EPI with progesterone (P) secretion. EPI also augmented hCG- and FSH-induced P secretion. The EPI effect was reproduced by Zinterol, a beta 2-adrenergic agonist and was prevented by propranolol, a beta-adrenergic antagonist. Blockade of alpha-adrenergic receptors with phentolamine was ineffective. It is suggested that EPI of adrenomedullary origin supports female prepubertal development by a) stimulating ovarian P secretion, b) favoring Prl and GH release and c) amplifying the stimulatory effect of low gonadotropin levels on ovarian steroidogenesis. The effects of EPI on ovarian function appear to be mediated by beta-adrenergic receptors of the beta 2 type.     

Role of prostaglandin F2alpha in ovulation.

Using radioimmunoassay procedures, the levels of plasma, uterine and ovarian prostaglandin (PG) F2alpha, and those of plasma estradiol and progesterone were measured in intact, hysterectomized or ovariectomized immature female rats pretreated with PMS and subsequent HCG. Occurrence of ovulation was confirmed at 8 hours after the HCG administration not only in the intact rats but also in the hysterectomzied rats. The levels of plasma estradiol and progesterone, and of uterine and ovarian PGF2alpha rose with the PMS injection alone, but they did not reach the peaks before the HCG administration. Both plasma estradiol and uterine PGF2alpha showed a peak at 2 hours after the HCG injection. These peaks were antecedent 2 or 6 hours before the peaks of ovarian and plasma PGF2alpha, respectively. However, such increase of uterine PGF2alpha does not seem to be indispensable for ovulation, because ovulation could occur in the hysterectomized rats. The levels of ovarian PGF2alpha showed a high plateau from 4 to 8 hours after the HCG injection, and then rapidly decreased after ovulation. The levels of plasma PGF2alpha peaked not only in the intact rats but also in the hysterectomized rats at 8 hours after the HCG treatment. But in the ovariectomized rats, this plasma PGF2alpha peak at 8 hours disappeared and there was no statistical change of plasma PGF2alpha throughout the PMS-HCG treatment. Plasma progesterone gradually increased and reached the maximum at 10 hours after the HCG injection. These results conclude that the main source of increased plasma PGF2alpha during the ovulatory process induced with the PMS-HCG treatment is the ovary, and it is strongly suggested that a rapid increase of PGF2alpha in the ovary may play some important role(s) in the ovulatory process.     

Formation of ovarian follicular cysts and corpora lutea after treatment with antihistamine or indomethacin in prepubertal gilts

Roles of histamine and prostaglandins in the induction of ovarian cysts after unilateral ovarian manipulation (MAN) and in the process of ovulation were evaluated in prepubertal gilts treated with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Administration of pyrilamine maleate, an H1 receptor antagonist, before MAN or hCG injection reduced the number of cysts formed but did not alter ovulation rate. Administration of cimetidine, an H2 receptor antagonist, failed to alter the incidence, number, or diameters of cysts formed in response to MAN or the ovulation rate on non-MAN ovaries. Administration of indomethacin, an inhibitor of prostaglandin synthesis, before MAN or hCG injection did not alter the incidence, number, or diameters of cysts formed on MAN ovaries but reduced the number of corpora lutea on non-MAN ovaries. Excessive accumulation of fluid in ovarian cysts apparently was mediated by histamine interacting with the H1-type receptor. Enhanced secretion of prostaglandins produced by the cyclooxygenase pathway did not contribute to development of ovarian cysts but, unlike histamine, was required for formation of corpora lutea in prepubertal gilts treated with PMSG and hCG.