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PubMed2001

Assessing human fertility using several markers of ovulation.

In modelling human fertility one ideally accounts for timing of intercourse relative to ovulation. Measurement error in identifying the day of ovulation can bias estimates of fecundability parameters and attenuate estimates of covariate effects. In the absence of a single perfect marker of ovulation, several error prone markers are sometimes obtained. In this paper we propose a semi-parametric mixture model that uses multiple independent markers of ovulation to account for measurement error. The model assigns each method of assessing ovulation a distinct non-parametric error distribution, and corrects bias in estimates of day-specific fecundability. We use a Monte Carlo EM algorithm for joint estimation of (i) the error distribution for the markers, (ii) the error-corrected fertility parameters, and (iii) the couple-specific random effects. We apply the methods to data from a North Carolina fertility study to assess the magnitude of error in measures of ovulation based on urinary luteinizing hormone and metabolites of ovarian hormones, and estimate the corrected day-specific probabilities of clinical pregnancy. Published in 2001 by John Wiley & Sons, Ltd.

Algorithms↗
PubMed1986

High susceptibility for diploidy in ovulated oocytes from XO mice.

Adult female mice of the "sensitive" NMRI/Han strain ovulate diploid oocytes after gonadotropin treatment. Other mouse strains are "non-sensitive" with respect to the ovulation of such diploid oocytes. In this study we combined the impaired ovarian situation in the XO karyotype with the trait "diploidy", which is determined genetically, by mating Ta/O (Ta = Tabby) females of C3H X 101 background to males of the NMRI/Han strain. The adult female F1 hybrids were stimulated to ovulation by gonadotropins and identified by their karyotype (XX or XO). The cytogenetic analysis of ovulated oocytes revealed a low level of diploidy in the XX littermates (1.0%), but a very high level in females with the XO karyotype (24.6%). All of the XO females ovulated at least one diploid oocyte. We suggest that it is the XO status which drastically impairs meiosis I in our "gonadotropin-sensitive" F1 females due to (1) alterations of the developmental program within the oocyte, (2) a disturbed communication between oocyte and follicle, (3) a preferential maturation and ovulation of "follicles at risk", or (4) an exceptional recruitment of many such follicles, by, e.g., a premature responsiveness to gonadotropins in our XO females. An interdependence of several such mechanisms is possible.

Animals↗
PubMed1989

The accuracy of urinary luteinizing hormone testing in predicting ovulation.

Transvaginal ultrasonography and daily urinary luteinizing hormone testing were used to evaluate the accuracy of urinary luteinizing hormone testing in predicting ovulation in 33 spontaneously ovulating women beginning on cycle day 10. Ovulation was confirmed in all patients with luteal phase progesterone levels and endometrial biopsy specimens. The results demonstrated that transvaginal ultrasonography and urinary luteinizing hormone testing detected ovulation in all cycles. However, the onset of urinary luteinizing hormone occurred after follicle rupture was documented by ultrasonography in 9% of the women studied. Thus the question of accuracy of urinary luteinizing hormone testing in prediction contrasted to detection of ovulation is raised. This observation is of importance in patients in whom prediction of ovulation is critical to treatment management. Therefore, an ultrasonographic examination to confirm the presence of an unruptured follicle on the day of onset of urinary luteinizing hormone surge is recommended, particularly in patients failing to conceive after three to six cycles of artificial insemination when the inseminations are timed with the onset of urinary luteinizing hormone surge.

Adult↗
PubMed1992

Inhibition of ovulation in the gonadotropin-primed immature rat by exogenous prostaglandin E2.

In the past two decades there have been innumerable reports that prostaglandins (PGs) are essential for mammalian ovulation. However, we have recently found that a relatively low dose of 0.03 mg indomethacin (INDO) sc to PMSG/hCG-primed immature Wistar rats can significantly reduce ovarian PG levels without inhibiting the control ovulation rate of 60+ ova/rat (1-3). In view of this information, the present study was an effort to duplicate the earlier reports that PGs can reverse the "inhibitory" effect of INDO on ovulation. In control animals, which received PMSG and hCG only, the ovulation rate was 63.8 +/- 4.5 ova/rat. This rate was reduced to 4.1 +/- 1.1 ova/rat when the animals were injected with 1.0 mg INDO at 3 h after hCG. In no instance was this inhibition reversed when the animals were treated with 1.0 mg of PGE2 or PGF2 alpha, or a combination of both prostanoids in either a single dose at 3 h after hCG, or in 4x doses at 2-h intervals beginning at 3 h after hCG. Furthermore, in animals that did not receive INDO, the ovulation rate in PGE2-treated animals was reduced to 20.0 +/- 6.7 ova/rat, and in animals treated with PGE2 and PGF2 alpha (combined) it was reduced to 19.4 +/- 6.5 ova/rat. In summary, not only did the PGs fail to reverse the anti-ovulatory effect of INDO, PGE2 actually suppressed the ovulation rate.

Animals↗
PubMed2006

Synchronization of estrus and ovulation in sows not conceiving in a scheduled fixed-time insemination program.

A field study was conducted to investigate the effectiveness of a treatment with altrenogest, eCG and hCG or the GnRH-analogue D-Phe(6)-LHRH to synchronize estrus and ovulation of sows diagnosed as non-pregnant in order to reintegrate them back into a scheduled fixed-time insemination program. Sows (n=531) diagnosed as non-pregnant by ultrasonography on days 21-35 after insemination were subjected to one of three treatments: (1) 16 mg altrenogest/day/animal orally for 15 days to block follicular growth, followed by injection of 1000 IU eCG intramuscularly (i.m.) 24h after withdrawal of altrenogest to stimulate follicular growth and 500 IU hCG i.m. 78-80 h after eCG to induce ovulation; (2) similar to (1) except that 20mg altrenogest and 800 IU eCG were used and (3) similar to (2) except that 50 microg D-Phe(6)-LHRH was used to induce ovulation. Females were artificially inseminated (AI) twice at 24 and 40 h, respectively, after hCG/D-Phe(6)-LHRH. Success of treatments was checked by ultrasonography of the ovaries. Rates of conception and farrowing (CR, FR), and number of total and live born piglets (TB, LB) were recorded and compared to those of synchronized first served sows. Females had differing ovarian structures prior to treatment. Altrenogest effectively blocked follicular growth in >80% of the females irrespective of dosage, but 16 mg increased the development of polycystic ovarian degeneration. Four to 18% of the females still had corpora lutea after altrenogest. Most females ovulated either between both inseminations or thereafter (P<0.05). Females treated with D-Phe(6)-LHRH tended to ovulate earlier than those injected with hCG. The CR and FR were up to 25% lower for sows diagnosed as non-pregnant than for sows after first service (P<0.05). Among sows diagnosed as non-pregnant the CR was higher in females treated with D-Phe(6)-LHRH (P<0.05). No differences were found in regard to numbers of TB and LB. In conclusion, a treatment with 20mg altrenogest per day per animal, followed by 800 IU eCG and 50 microg the GnRH-analogue D-Phe(6)-LHRH is appropriate to synchronize estrus and ovulation of sows diagnosed as non-pregnant. Whether there might be a need to feed altrenogest for a longer interval of 18 days has to be investigated.

Animals↗
PubMed1980

Return of ovulation after abortion and after discontinuation of oral contraceptives.

The return of ovulation after abortion and discontinuation of oral contraceptives was determined by plasma progesterone measurements. Plasma samples were obtained from 67 women at 3 to 6 weeks after abortion and in two groups of postabortion women at 3 to 6 weeks after cessation of oral contraceptives. In the first of these latter two groups, 50 women started taking the pills (containing 30 microgram of ethinylestradiol and 150 microgram of levonorgestrel) immediately after abortion, and the second group of 29 women started taking the pills from the first postabortion menses. Ovulation had recurred in 34% of the women 3 weeks after abortion and in 78% of the women at 6 weeks. The return of ovulation had occured in approximately 55% at 3 weeks after cessation of oral contraceptives in both groups. At 6 weeks after cessation, approximately 85% of women had ovulated in both groups. Luteal function in these two groups was found to be equal and was significantly better in both groups than during the first postabortion cycle (P < 0.005). It is concluded that the early return of ovulation after abortion makes it necessary to commence effective contraception immediately after abortion. The immediate administration of oral contraceptives after abortion does not affect the return of ovulation after discontinuation of oral contraceptives.

Abortion, Legal↗
PubMed1985

Urinary 6-keto-prostaglandin F1 alpha during ovulation induction.

To elucidate the role of the vasodilatory prostacyclin (PGI2) in human ovulation, urinary samples were collected from spontaneously ovulating women (n = 8) and from those undergoing ovulation induction with clomiphene (seven women, 9 cycles) and human gonadotropins (five women, 11 cycles). The samples were assayed for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a breakdown product of PGI2, employing high-pressure liquid chromatography and radioimmunoassay. The urinary 6-keto-PGF1 alpha was not consistently related to the menstrual cycle day at collection, the occurrence of spontaneous (n = 8) or induced (n = 11) ovulation, or the simultaneous concentration of estradiol in plasma. However, its concentrations both before and after the approximated time of ovulation during clomiphene (41.6 +/- 6.7 and 52.7 +/- 7.9 pmol/mmol creatinine, before/after, mean +/- standard error) or gonadotropin treatment (49.0 +/- 5.8 and 48.1 +/- 6.8 pmol/mmol creatinine) were higher (P less than 0.01) than those in spontaneously ovulating women (26.4 +/- 3.8 and 20.5 +/- 3.0 pmol/mmol creatinine, respectively). Multiple ovarian follicles, as assessed ultrasonographically, developed during four courses of the treatments with gonadotropins, and in three of them the urinary 6-keto-PGF1 alpha was high. The data suggest that treatment with clomiphene and gonadotropin is accompanied by increased production of PGI2, perhaps in the ovaries and/or in the kidneys. This may perhaps play a role in the etiopathogenesis of ovarian hyperstimulation syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

RU486 inhibits ovulation, fertilization and early embryonic development in rabbits: in vivo and in vitro studies.

OBJECTIVE: To clarify the role of P in ovulation, fertilization, and early embryonic development using RU486, a potent P receptor blocker. DESIGN: Ovulatory efficiency, IVF, and early embryonic development were evaluated after RU486 administration in vivo and in vitro. SETTING: Research laboratory of a university hospital. PARTICIPANTS: Mature male and female New Zealand white rabbits. INTERVENTIONS: Animals were treated with RU486 or vehicle for 3 days before hCG-induced ovulation. Ovaries treated with hCG to induce ovulation were perfused for 6 hours in vitro with RU486 or vehicle. In vitro fertilization was performed in the presence or absence of RU486. MAIN OUTCOME MEASURES: The percentage of mature follicles ovulating (ovulatory efficiency) was determined after in vivo and in vitro treatment. Fertilization, morula, and blastocyst development were evaluated every 24 hours for 120 hours. RESULTS: RU486 significantly inhibited ovulation, fertilization, and early embryonic development. CONCLUSIONS: Progesterone plays a significant role in ovulation, fertilization, and preimplantation embryonic development.

Animals↗
PubMed2000

The time of ovulation in relation to estrus duration in gilts.

The objective of this study was to determine time of ovulation, monitored by transcutaneous ultrasonography, relative to the duration of estrus in gilts. We exposed 92 cyclic gilts, Camborough x Canabrid terminal line, at Day 19 of their third estrous cycle to vasectomized boars every 6 h for the detection estrus. Transcutaneous ultrasonography was performed every 6 h, starting 24 h after the onset estrus, to determine time of ovulation. Estrus duration was, on average, 52.6 h (range: 30 to 72 h), and ovulation occurred between 30 and 60 h after the onset of estrus (mean: 44 h), about 85 % of the way through the estrus period. The time of ovulation during estrus was dependent on the duration of estrus (Time of ovulation = (duration of estrus) x 0.409 + 22.7; r = 0.57, P = 0.0001). Prediction of the time of ovulation in relation to duration of estrus is important for determining the optimal time for inseminating gilts. This knowledge would contribute to an improvement in the fertilization rate and in reproductive efficiency of the breeding herd.

Animals↗
PubMed2001

Effects of maturity of the potential ovulatory follicle on induction of oestrus and ovulation in cattle with oestradiol benzoate.

The effect of maturity of the dominant follicle (DF) on the capacity of oestradiol benzoate (ODB) to induce oestrus and ovulation was examined in cattle. In experiment 1, 31 prepubertal heifers each received an intravaginal progesterone insert (IPI) and 1mg ODB i.m./500kg BW (ODB1). Daily ovarian ultrasonography detected emergence of a new follicular wave 3.1+/-0.1 days after ODB1. The IPI was removed when newly emerged DF were "young" (1.3+/-0.1 days after emergence; YDF; n=15) or "mature" (4.2+/-0.1 days; MDF; n=16), and 24h later, heifers received 0.75mg ODB/500kg BW (ODB2; n=16) or no further treatment (NoODB2; n=15). Most of the heifers receiving ODB2 were observed in oestrus (15/16) and ovulated (12/16), as compared to 0/15 and 1/15 in the NoODB2 group, respectively (P<0.01). In experiment 2, 32 heifers received ODB1 on day 6 of the oestrous cycle, and new follicular wave emergence was detected 3.2+/-0.1 days later. Heifers received an injection of prostaglandin-F2alpha (PGF) when the DF was young (1.1+/-0.1 days after emergence; YDF; n=16) or mature (4 days; MDF; n=16), and then ODB2 24h later or no further treatment (NoODB2). The interval from PGF to oestrus was greater (P<0.01) in the YDF-NoODB2 (70+/-3.9h) as compared to MDF-NoODB2 group (57+/-1.8h). Inclusion of ODB2 reduced (P<0.01) this interval to 47.0+/-0.7h without regard to the maturity of the DF (maturityxODB2, P<0.05) and also reduced (P<0.05) the interval to ovulation. In experiment 3, 21 suckling anoestrous cows received an IPI and ODB1 at 29.3+/-1.7 days postpartum. The IPI were removed either 1 day (YDF; n=9) or 3.9+/-0.1 days (MDF; n=9) after emergence of a new follicular wave and every cow received ODB2. Oestrus was subsequently detected in all but one animal. Ovulation of the newly emerged DF was detected within 48h of ODB2 in nine of nine cows of the MDF group, and in four of nine of the YDF group (P<0.05). During the subsequent ovulatory cycle, luteal size and plasma concentrations of progesterone were greater (P<0.01) in the MDF group compared to the YDF group. We conclude that behavioural oestrus is readily induced by 0.75mg ODB i.m./500kg BW. Maturity of the DF appeared to have little influence on the ability of the DF to ovulate in heifers. In contrast, young DF in lactating anoestrous cows were less likely to respond to the ovulatory cue provided, and luteal development was compromised in those that did ovulate.

Administration, Intravaginal↗
PubMed1992

Time of ovulation in merino ewes superovulated with PMSG and FSH-P.

An experiment examined the effects of treatment with gonadotrophin releasing hormone (100 micrograms GnRH injected 24 h after progestagen sponge removal), season of treatment (autumn v. spring), the effect of supplementary feeding with lupin grain (in autumn only, from 12 days before until 8 days after sponge removal) on the time of ovulation in 182 mature Merino ewes superovulated with a combination of 400 I.U. pregnant mare serum gonadotrophin (PMSG) and 12 mg follicle stimulating hormone (FSH-P). Time of ovulation was influenced by both season and the administration of GnRH. Two peaks of ovulation were observed in spring, the first between 24 and 30 h after sponge removal, and the second commencing 42 h after sponge removal. In autumn, there was one peak of ovulation between 42 and 54 h after sponge removal. Treatment with GnRH advanced the time of ovulation in autumn (P less than 0.05), but had no apparent effect in spring. In contrast to the effect of GnRH, time of ovulation for ewes treated in autumn was delayed (P less than 0.001) by supplementary feeding with lupins.

Animal Feed↗
PubMed1992

Luteinizing hormone requirements for ovulation in the rat.

Luteinizing hormone requirements for ovulation induction were studied in proestrous rats through detailed observation of the preovulatory surge, through various forms of LH injection under sodium pentobarbital blockade, and through estimation of LH uptake by the ovary. Blood LH levels in individual proestrous rats were obtained every 30 min and grouped according to their peak time (designated 0 h); mean LH levels higher than 7 and 5 ng/ml continued for 30 min and 2.5 h, respectively, the pituitary LH contents at 1400 and 2000 h on the day of proestrus were 2.1 and 0.7 micrograms, respectively, indicating that the amount of LH secreted during the surge was at least 1.4 micrograms. Single intravenous injections of 2 micrograms and 1 micrograms of pure rat LH (NIDDK-rLH-I-7; FSH and prolactin contaminations: 0.02% and less than 0.01%, respectively) to sodium pentobarbital-blocked rats induced ovulation in 4 out of 4 rats and 4 out of 6 rats, respectively, while 500 ng failed to induce ovulation in any (out of 7) rats. Two injections of 300 ng each with an interval of 20 min induced ovulation in 3 out of 8 rats, but if the interval was prolonged to between 30 and 120 min, 100% ovulation was obtained. Blood LH levels in these experiments indicated that a lower long-lasting LH level (about 5 ng/ml blood) is more important than a short, high level for ovulation induction. It was also shown that this level of LH could be given in separate doses if the interval was 30-120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Development and characterization of an in vitro ovulation model using mouse ovarian follicles.

To investigate ovulation, an in vitro model with cultured mouse follicles was developed and compared with an in vivo ovulation model. In this model, secondary follicles were grown in vitro with immature mouse serum (5%) and recombinant human FSH. Addition of ascorbic acid and selenium to the medium increased follicular survival (from 29% to 86%) and resulted in the development of healthy preovulatory follicles (> 400 microm) producing estradiol. Depending on the starting size of the follicles, the preovulatory stage was reached after 4-6 days. The ovulatory response to hCG was maximal in follicles exceeding a diameter of 400 microm. The in vitro-ovulated oocytes could be fertilized and were able to develop to the blastocyst stage. Ovulation induced by hCG was dose dependent, reaching a maximum of 80% at 1 IU/ml. Concomitantly, progesterone production increased from 3.6 +/- 0.5 to 29 +/- 2 ng/ml. Both in vivo and in vitro, hCG induced expression of the progesterone receptor and the prostaglandin endoperoxide synthase-2 (PGS-2) gene within 3 h. Ovulation could be completely blocked with the anti-progestogen Org-31710 and partially (50%) with the PGS inhibitor indomethacin in vitro and in vivo. Org-31710 and indomethacin did not affect progesterone production. In summary, a physiologically relevant in vitro ovulation model of cultured mouse follicles that can be used to study the process of follicular rupture has been developed.

Animals↗
PubMed1995

Application of a method for estimating day of ovulation using urinary estrogen and progesterone metabolites.

Longitudinal epidemiologic studies of menstrual and reproductive function are more informative if one can identify day of ovulation. We previously developed a method for estimating day of ovulation that is feasible for epidemiologic studies. The method relies on the relative concentrations of estrogen and progesterone metabolites in daily first-morning urine specimens and does not require creatinine adjustment. This paper describes results of applying this method to a large study with 724 menstrual cycles from 217 women. The method estimated a credible day of ovulation in 88% of cycles. Missing data accounted for most of the failures. When we excluded anovulatory cycles (1%) and cycles with missing data, the method estimated a day of ovulation in 97% of cycles. Variance in luteal phase length was small for our sample, suggesting that this method of identifying a day of ovulation introduces no more measurement error than when day of ovulation is determined by plasma luteinizing hormone (LH), the standard clinical method.

Adult↗
PubMed2002

Validity of methods for analyzing urinary steroid data to detect ovulation in athletes.

PURPOSE: The purpose of this study was to determine whether the accuracy of ovulation detection algorithms is compromised when applied to menstrual cycles exhibiting subclinical hormonal abnormalities, which are particularly prevalent in female athletes. METHODS: The validity of five ovulation detection algorithms was compared between 25 regularly exercising women and 15 sedentary controls. Subjects collected daily urine samples for an entire menstrual cycle for analysis of estrone-3-glucuronide (E1G), pregnanediol-3-glucuronide (PDG), and luteinizing hormone (LH). The algorithms were applied to determine their sensitivity (% of true ovulatory cycles), specificity (% of true anovulatory cycles), and the deviation from the reference day of ovulation (difference scores). RESULTS: The sensitivity was > 80% in all algorithms except Baird's E1G/PDG ratio algorithm (74%) and Kassam's PDG ratio algorithm (78%). All algorithms, except Kassam's PDG ratio algorithm (80%), were found to exhibit specificities < 70%. Baird's E1G/PDG ratio algorithm was the most accurate in estimating the day of ovulation by deviating only -0.2 +/- 0.3 d from the reference day in the exercising female cycles and -0.5 +/- 0.3 d in the controls. No statistical differences in the sensitivities of the algorithms were found between the exercising and control cycles. When comparing the deviation from the reference day of ovulation between subject groups, no statistical difference was found. CONCLUSION: The algorithms display similar validity in determining the presence and day of ovulation between subject groups, and thus may be applied to cycles exhibiting subclinical hormonal abnormalities as commonly observed in exercising women.

Adolescent↗
PubMed1993

Transient and cell-specific expression of tissue-type plasminogen activator and plasminogen-activator-inhibitor type 1 results in controlled and directed proteolysis during gonadotropin-induced ovulation.

Proteolytic activity generated by the plasminogen-activator system (PA system) is associated with many biological processes. However, it is not known how the proteolytic activity is regulated in vivo in order to obtain directed proteolysis while, at the same time, protecting unrestrained tissue destruction. Using gonadotropin-induced ovulation as a model, we have studied how two components of the PA system, tissue-type plasminogen activator (tPA) and plasminogen-activator-inhibitor type 1 (PAI-1), are regulated temporally and spatially by gonadotropins, leading to the initiation and termination of a well-directed proteolytic process. In-situ hybridization and in-situ zymography were used to analyze the expression of tPA and PAI-1 mRNA and PA-activity in specific ovarian cell types. Both tPA and PAI-1 were found to be regulated and to have a distinct expression pattern in different ovarian compartments. tPA was expressed in both granulosa and thecal-interstitial cells; the highest levels of tPA mRNA were found in the granulosa cells of preovulatory follicles, just prior to ovulation. Consistent with a role for luteinizing hormone/chorionic gonadotropin (LH/CG) in triggering ovulation, the cells and follicles that actively expressed tPA also contained high levels of LH-receptor mRNA while cumulus cells that contain undetectable amounts of tPA mRNA were devoid of LH-receptor expression. The highest levels of PAI-1 mRNA were found about 6 h before ovulation and mainly in the thecal-interstitial cells and ovarian stroma tissue which encapsulate the follicle. Preovulatory follicles, protruding onto the surface of the ovary with less surrounding stroma tissue, expressed less PAI-1 compared to small non-ovulatory follicles embedded in inner part of the ovary. In-situ zymography also revealed that the PA activity was colocalized to the surface of the ovary just prior to ovulation. Our studies suggest that a proteolytic activity provided by tPA and modulated by PAI-1 is responsible for a controlled and directed proteolysis leading to rupture of selected follicles during ovulation.

Animals↗
PubMed1986

Efficacy of human chorionic gonadotrophin and gonadotrophin releasing hormone for hastening ovulation in thoroughbred mares.

Plasma progesterone levels were measured daily to determine the accuracy of diagnosing ovulation by rectal palpation carried out every other day; 81.5 per cent mares injected with human chorionic gonadotrophin showed increases of progesterone more than 1 ng/ml by 72 h after injection compared with 65 per cent of mares injected with gonadotrophin releasing hormone (GnRH) or saline. Mating at ovulation achieved a 74 per cent pregnancy rate in mares given hCG compared with 50 per cent given GnRH and 45 per cent controls. Diagnosis of ovulation per rectum on the basis of a pit in the ovarian surface or the presence of a soft friable structure was found to be accurate in 91 per cent of cases. Diagnosis based on the presence of a firm plum-like structure or the disappearance of a previously identified follicle at a given site was 60 per cent accurate. In cases of rectal diagnosis of non-ovulation 38 per cent had actually ovulated based on a rise in progesterone more than 1 ng/ml and a further 19 per cent showed a rise in progesterone by 24 h after the diagnosis. The use of hCG may improve conception rates by synchronisation of ovulation and mating and where rectal palpation of the ovaries remains the only basis for timed mating.

Animals↗
PubMed1991

Comparison of inhibitory actions of indomethacin and epostane on ovulation in rats.

Indomethacin, an inhibitor of cyclooxygenase that generates prostaglandins (PGs) from arachidonic acid, and 2 alpha,4 alpha,7-4,5-epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane- 2-carbonitrile (epostane), an inhibitor of 3 beta-hydroxysteroid dehydrogenase that generates progesterone from pregnenolone, are both potent inhibitors of ovulation. This report compares the dose-dependent effects of these two inhibitors on ovarian levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid methyl ester (HETEs), prostaglandin E2 (PGE), prostaglandin F2 alpha (PGF), progesterone, 17 alpha-hydroxyprogesterone, 17 beta-estradiol, 4-androstene-3,17-dione, and testosterone during ovulation in 25-day-old immature Wistar rats. The ovulatory process was initiated by 10 IU of human chorionic gonadotropin (hCG). Indomethacin was given at 3 h after hCG in doses ranging from 0.0316 to 10.0 mg/rat. A dose of 0.1 mg/rat was the lowest dose to significantly reduce the ovulation rate from the control level of 70.5 +/- 5.8 ova/rat. This dose also reduced 15-HETE, but not 5-HETE, 12-HETE, or the steroids. PGE and PGF were strongly inhibited by an even lower dose of indomethacin (0.0316 mg/rat), but this dose did not affect the ovulation rate. Epostane was given at 3 h after hCG in doses ranging from 0.1 to 5.0 mg/rat. A dose of 1.0 mg/rat was the lowest dose to significantly inhibit ovulation. This dose also reduced the ovarian levels of 15-HETE and progesterone but not 5-HETE, 12-HETE, PGE, PGF, or the other steroids. The results indicate that the ovulation rate is most closely correlated to ovarian 15-HETE levels.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗