Progesterone, but not luteal estrogen, is required for the establishment of pregnancy in the new world monkey Cebus apella

Abstract

The aim of this study was to examine the requirement of luteal progesterone or luteal estrogen for the establishment of pregnancy in the Cebus monkey and to test in a primate species the synergism between RU 486 and letrozole (LTZ) found in rodents for inhibiting implantation. Exposure of target tissues to either hormone was suppressed during the mid-luteal phase of mating cycles by subcutaneous administration of the antiprogestin (RU 486), the aromatase inhibitor LTZ or the antiestrogen (ICI 182780) on days 4-7 of the luteal phase. Administration of 0.1 or 0.5 mg/kg of LTZ on days 5-7 of the luteal phase caused a profound drop in the levels of E(2) in all animals, whereas administration of ICI 182780 0.2 mg/kg on days 4-6 of the luteal phase had the opposite effect. The pregnancy rate in vehicle treated cycles of the same females was (58.3%). Treatment with RU 486, 0.8 mg/kg/day on days 5-7 of the luteal phase-induced endometrial bleeding in 3/5 mated females none of which became pregnant, whereas pregnancy was confirmed in one of the two animals that did not bled. Treatment with RU 486, 0.4 mg/kg/day alone or with LTZ on days 5-7 or ICI 182780 alone, on days 4-6 of the luteal phase failed to induce bleeding, allowing the establishment of pregnancy in 50.0-66.6% of the animals in these groups. We conclude that in Cebus monkeys, progesterone but not luteal estradiol is required for the establishment of pregnancy and that RU 486 and LTZ do not exhibit in this species the synergism found in rodents.

As the world grows: contraception in the 21st century

“…The search for agents that work postovulation up to and including blastocyst attachment to the endometrium has been vigorously pursued for over 50 years. However, the animal models used in most studies were rats or mice, which eventually proved to be unsuitable, since they require ovarian estrogen to initiate the process of implantation, whereas primates do not (125,126). Hence, selective estrogen receptor modulators (SERMs) will not be contraceptives in women.…”

Endometrial maturation: the role of oestradiol and progesterone

“…We were able to make a clear distinction between genes that are regulated by progesterone irrespective of the presence of oestradiol, and genes of which the expression clearly is influenced by the continuous presence of oestradiol, which would suggest that both oestradiol and progesterone are needed for successful embryo implantation. However, studies in the new world monkey Cebus paella treated with an ER antagonist, ICI 182780 on days 4-7 of the luteal phase [344], ovariectomized rhesus macaques receiving a surrogate embryo transfer [84] and women [345,346], do not support an essential role for luteal phase ovarian oestrogen in implantation and maintenance of pregnancy.…”