Rosemarie Thau

Effects of Immunization with the β-Subunit of Ovine Luteinizing Hormone on Corpus Luteum Function in the Rhesus Monkey * †

Rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLHbeta) developed circulating antibodies which cross-reacted strongly with rhesus monkey chorionic gonadotropin. Normal ovulatory cycles continued, but the fertility of immunized monkeys as compared with that of controls was significantly reduced. Thus, the rhesus monkey represented a useful animal model for the study of certain aspects of an antifertility vaccine. We investigated the effects of circulating antibodies to oLHbeta on corpus luteum function by measuring production rates (PRs) and peripheral concentrations of progesterone during the luteal phase of the menstrual cycle. Both parameters were significantly lower in immunized animals than in control animals. The length of the menstrual cycle was also significantly reduced. Progesterone PRs were also determined on days 10 and 15 after mating to test the assumption that the antifertility vaccine prevents pregnancy by interfering with corpus luteum rescue (the increase in PRs of progesterone usually occurring on day 15 after mating in fertilized animals). PRs increased from days 10 to 15 in pregnant controls, were unchanged in nonpregnant controls, and were significantly lower on day 15 in immunized monkeys as compared with nonpregnant and pregnant controls. These results suggest that corpus luteum rescue is suppressed in immunized animals.

The Mechanism of Action of an Antifertility Vaccine in the Rhesus Monkey: Reversal of the Effects of Antisera to the β-Subunit of Ovine Luteinizing Hormone by Medroxyprogesterone Acetate *

Active immunization of female rhesus monkeys with the beta-subunit of ovine luteinizing hormone )oLH beta) significantly reduced their fertility. To determine whether the major action of the vaccine was interruption of pregnancy, by suppression of corpus luteum rescue, or inhibition of ovulation, we administered the progestational agent medroxyprogesterone acetate (MPA) from day 4 through day 40 after mating. In the untreated immunized group, the pregnancy rate was significantly below that of control monkeys. MPA treatment restored the fertility rate of immunized animals to that of the control group. These results strongly support the assumption that the antifertility action of antibodies of oLH beta is due to prevention of corpus luteum rescue. Whether the lack of corpus luteum rescue resulted because of neutralization of rhesus monkey chorionic gonadotropin or from a defective corpus luteum, as is found in animals with short luteal phases, cannot be determined from these studies. The successful reversal of the antifertility effect, however, suggests that the circulating antibodies do not interfere with normal ovulation or with the normal development and implantation of the blastocyst.

Premature Induction of Labor with Dilinoleyl Lecithin in Rabbits

Extract: Dilinoleyl lecithin (DLL), identified as a component of a crude mixture of soya bean phospholipids (SBP), was obtained in highly pure form by synthesis. The DLL was administered to 25-day pregnant rabbits in doses of 1.0 and 2.0 g/rabbit. One unit of oxytocin was administered intramuscularly 24, 48, and 49 hr after infusion, and the rabbits were observed for abortion. The abortion rate after the 1.0-g dose of DLL was 56.9 ± 6.9% and that after the 2.0-g dose was 100.0 ± 0%; the rate in controls was 2.6 ± 2.6%.Speculation: Dilinoleyl lecithin, a biochemically defined component of SBP, was found to be capable of reproducing the biologic activity of SBP in prematurely sensitizing the pregnant rabbit uterus to oxytocin. The mode of action of both DLL and SBP is unknown, but two possibilities appear likely: (1) the linoleic acid (or, for SBP, perhaps other “essential” fatty acids as well) available from lecithin is converted to a prostaglandin, which in turn sensitizes the rabbit uterus to oxytocin or (2) DLL in some way reduces the amount of progesterone available to maintain the pregnancy. The latter possibility does not necessarily exclude the former, inasmuch as certain prostaglandins are known to be luteolytic.

PROLONGED |[ldquo]|GESTATION|[rdquo]| FOLLOWING FETECTOMY IN MONKEYS

A fetal influence over gestation time is recognized in several mammals; clarification of the mechanisms involved might suggest approaches to the prevention of prematurity. Fetal pituitary or adrenal defects lead to prolonged gestation, and ACTH or glucocorticoid administration can induce premature labor. We have attempted to distinguish fetal and placental mechanisms by performing fetectomy in macaques. Fetuses were removed from 10 monkeys at gestation ages from 65 to 143 days; placentas were left in situ. Of the 10 placentas, 7 were carried past normal term (155-176 days), and were delivered at 181 to 243 days. Four were delivered spontaneously and 2 after giving dexamethasone; 1 was removed surgically. At fetectomy, plasma progesterone values were highest in the umbilical vein, lower in fetal heart and uterine vein, and lowest in maternal peripheral vein. Following fetectomy, maternal progesterone values remained at or above normal pregnancy levels until placental expulsion or shortly before. Following expulsion, values fell promptly to non-pregnancy levels. Estradiol values (5 animals) fell within 7 to 19 days after fetectomy to 1/3 of pre-fetectomy levels and the rise normally seen before delivery did not occur prior to expulsion. These results indicate that in the absence of the fetus, delivery of the placenta is usually delayed, but that the ability of a glucocorticoid to precipitate expulsion remains. Maternal plasma progesterone levels are maintained, but estradiol levels fall.