Urine samples were collected daily during ten nonfertile and four fertile ovarian cycles of four adult female lion-tailed macaques (Macaca silenus). Urine was analyzed for concentrations of total immunoreactive estrogen (Et), estrone conjugates, and bioactive luteinizing hormones (LH). The estrone conjugates of selected samples were separated by high-performance liquid chromatography (HPLC) to evaluate the relative proportions of estrone glucuronide (E1 G) to estrone sulfate (E1 S) contributing to the sum total of the conjugate measured in the samples. The estrone conjugate profile was found to accurately reflect the preovulatory estrogen peak in both nonfertile and fertile cycles as well as the early pregnancy increase which was found to be statistically significant on Day + 14 postovulation (P = 0.003). Estrone conjugate levels rose in the early follicular phase from 126.00 +/- 24.07 (SEM) ng/mg creatinine to a preovulatory peak of 471.90 +/- 62.95 ng/mg creatinine. Fertile cycles exhibited a postovulatory climb to a peak of 515.00 +/- 38.00 ng/mg creatinine on Day + 19, in contrast to the secondary rise observed in nonfertile cycles that peaked at 148.11 +/- 13.80 ng/mg creatinine on Day + 10. Bioactive LH evaluations confirmed ovulation and, in the fertile cycles, reflected the subsequent elevation of chorionic gonadotropin on Day + 18. The estrone conjugate profile of fertile cycles and early pregnancy compared favorably to the Et profile: both showed the same time course and increases in estrogen excretion.
Administration of varying doses (10-50 micrograms) of deglycosylated human CG (DG-hCG) which was previously shown to be a potent hormonal antagonist in vitro, to pregnant rats inhibited implantation and terminated gestation. When administered between days 1-5 implantation was inhibited as seen on day 10. Serum progesterone levels were also suppressed. Similar doses administered between days 8 and 11 resulted in complete fetal resorption when examined on day 16. This was also accompanied by a dramatic reduction in serum progesterone. A dose of 50 micrograms DG-hCG given during the second half of pregnancy between days 13 and 16 had no deleterious effect on pregnancy including the day of parturition but the number of pups delivered was reduced by 26% as compared to 3% loss in control groups. It is concluded that DG-hCG can successfully antagonize hormone action in vivo by blockade of ovarian receptor sites for LH in the pregnant rat.
The effects of the dopamine antagonist pimozide on the preimplantation delay phase of mink gestation were investigated in field and laboratory trials. Three doses of 0.1 mg pimozide in acetic acid administered on the 7th, 9th and 11th days after mating abbreviated gestation in Pastel kit female mink to a mean (+/- SEM) of 45.5 +/- 0.5 days, 10 days less than that observed in mink treated with vehicle only (55.6 +/- 0.6 days). In laboratory trials, four doses of 0.1 mg pimozide on the 7th, 9th, 11th and 13th day after mating resulted in embryo implantation at a mean of 25 +/- 4.3 days after mating while vehicle-treated control animals had mean preimplantation delay of 37 +/- 3.1 days. Luteal activation in the pimozide-treated group, as indicated by a rapid increase in circulating progesterone, began within 2 days after the first pimozide injection. No increase was observed in vehicle-treated mink until 6 or more days after the initiation of injections or 13 days after mating. It was concluded that pimozide, presumably by permitting endogenous secretion of prolactin, can induce precocious luteal activation and embryo implantation in the mink.
Subcutaneous injection of serotonin (20 mg/kg) on Day 5 of pregnancy disrupts implantation in the rat as indicated by the reduction in number of live fetuses/cornu present on Day 19 (0.9 vs. 6.1, treated vs. control). Such disruption of implantation possibly results from impaired decidualization. To test for suppression of decidualization, serotonin was administered to pseudopregnant rats on the day before, on (Day 4) or after artificial induction of the decidual cell reaction. Relative to saline-treated controls (C), serotonin (S) reduced decidualization when injected either before [C: 1987 +/- 130 vs. S: 1085 +/- 155 mg (Day 3); P less than 0.005] or after [C: 1987 +/- 130 vs. S: 173 +/- 8 mg (Day 5); P less than 0.001] administration of the deciduogenic stimulus. In addition, serotonin markedly decreased uterine blood flow (C: 0.47 +/- 0.05 vs. S: 0.25 +/- 0.06 ml/min per g; P less than 0.01) during pseudopregnancy. However, serotonin altered neither the duration of luteal function in pseudopregnant rats (C: 15.3 vs. S: 14.3 days) nor serum progesterone levels (C: 74-91 vs. S: 53-82 ng/ml) in pregnant animals. It is concluded that serotonin may disrupt implantation, in part, by suppression of decidualization. The loss of endometrial competence to undergo decidualization appears to be a consequence of serotonin-induced uterine ischemia rather than impaired corpus luteum activity.