| Title: | Effect of follicular phase administration of mifepristone (RU486) on blastocyst implantation in the rhesus monkey |
| Author(s): | Ghosh D; Nayak NR; Sengupta J; |
| Address: | "Department of Physiology, All India Institute of Medical Sciences, New Delhi, India" |
| DOI: | 10.1016/s0010-7824(97)00101-7 |
| ISSN/ISBN: | 0010-7824 (Print) 0010-7824 (Linking) |
| Abstract: | "In the present study our aim was to test two hypotheses: 1) inhibition of preovulatory phase progesterone action can inhibit or delay ovulation, and 2) inhibition of preovulatory phase progesterone action can inhibit postovulatory phase endometrial receptivity for blastocyst implantation. Female rhesus monkeys showing normal cycle lengths were randomly assigned to two groups: group 1 (n = 5) and group 2 (n = 7). The pretreatment cycles were monitored for ovulatory pattern and, in treatment cycles, females were allowed to cohabit with males from cycle days 6 to 28; group 1 animals received vehicle alone, and group 2 animals received mifepristone (RU486, subcutaneously), 1 mg/animal 3 consecutive cycle days (days 7, 8, and 9 for 26-day pretreatment cycle length; and days 8, 9, and 10 for 28-day pretreatment cycle length). Follicular phase mifepristone resulted in a delay of ovulation (p < 0.01) when compared with pooled data of pretreatment and treatment cycles of group 1 and pretreatment cycles of group 2. Despite delay of ovulation, there was only a 20% decrease in the incidence of pregnancy in group 2 as compared with that in group 1. However, a delay (p < 0.05) in the appearance of CG was noted in follicular phase mifepristone-treated cycles as compared with control treatment cycles. On the other hand, ovulation could not be detected in three monkeys in group 2; and, of these, two cycles were extended, but all three cycles were negative for CG. These results support earlier reports that follicular phase mifepristone can inhibit or disrupt follicular maturation, and delay ovulation. However, follicular phase mifepristone failed to inhibit implantation, because gonadal hormones, including progesterone, resume normal functions once ovulation takes place. Available research evidence suggests that, when administered during the follicular phase, a high affinity antiprogestin such as mifepristone can act at different levels of the hypothalamus-pituitary-ovary-uterus axis, resulting in contraceptive action. The administration of mifepristone during the late follicular phase of naturally mated cycles of rhesus monkeys was used to test the hypotheses that inhibition of preovulatory phase progesterone action can: 1) inhibit or delay ovulation, and 2) inhibit postovulatory phase endometrial receptivity for blastocyst implantation. During the preovulatory period, group 1 monkeys (n = 5) were treated with 1 mL vehicle and group 2 animals (n = 7) received mifepristone for 3 consecutive days. Peripheral hormone profiles suggested no ovulation occurred in 3 of 8 mifepristone-treated cycles. Follicular phase mifepristone treatment was associated with a delay of ovulation in 4 of 8 treated cycles. Despite the delay of ovulation, there was only a 20% decrease in the incidence of pregnancy in group 2 compared to group 1. A delay in the appearance of chorionic gonadotropin was noted in follicular phase mifepristone-treated cycles. These findings confirm that mifepristone treatment during the late follicular phase can inhibit or delay ovulation without affecting uterine function during the luteal phase. Further studies are required using this primate model to investigate the role of progesterone and other physiological modulators on ovulation and implantation. eng" |
| Keywords: | "Animals Blastocyst/*drug effects Embryo Implantation/*drug effects Female *Follicular Phase Hormone Antagonists/*pharmacology Macaca mulatta Mifepristone/*pharmacology Pregnancy Progesterone/*antagonists & inhibitors *Animals, Laboratory Biology *Clinical;" |
| Notes: | "MedlineGhosh, D Nayak, N R Sengupta, J eng Research Support, Non-U.S. Gov't 1997/08/01 Contraception. 1997 Aug; 56(2):117-22. doi: 10.1016/s0010-7824(97)00101-7" |
