Maintenance of pregnancy in ovariectomized rats with steroid analogs and the reproductive ability of the progeny.

The quantity of and the temporal requirements for natural steroids and steroid analogs were studied over the course of pregnancy after ovariectomy. A series of experiments determined that progesterone (3 mg/day) maintains the free blastocyst and when subsequently combined with estradiol supports implantation, and pregnancy through Day 20. The amount of estradiol (100 ng/day) that adequately induces blastocyst implantation and supports pregnancy through Day 13 had to be continued throughout pregnancy to prevent fetal resorption. Fetal survival was benefited if the estradiol dose was doubled from Day 13 to termination. During this study a within strain difference appeared which reduced the number of blastocysts that implanted. This problem was resolved by ovariectomizing the pregnant rats on Day 4 before 1000 h rather than on Day 3. Substitution of dydrogesterone (9 beta, 10 alpha-pregna-4, 6-diene-3, 20-dione) for progesterone on an equal weight basis and diethylstilbestrol (DES) for estradiol (2 for 1) proved adequate to maintain pregnancy to term. The pups were delivered by cesarean section and raised by surrogate mothers. As the females matured they experienced normal first estrus and subsequent estrous cycles. When bred they had litters of normal numbers. The males were fecund and sired litters of normal numbers. The cross-reactivity of dydrogesterone in estrogen, testosterone, corticosterone, progesterone and 20 alpha-hydroxy-pregn-4-one-3-one radioimmunoassays was nil. Thus, steroid analogs can adequately support the entire course of pregnancy after fertilization in ovariectomized rats.