Embryo mortality and altered uterine luminal proteins in progesterone-treated rabbits

This study was undertaken to elucidate the location, time, and nature of embryo mortality induced by preovulatory progesteron administration. Progesterone was injected into rabbits on days -2, -1, and 0 (the day of mating) at doses of 0.5, 1.0, and 1.0 mg, respectively. Normal fertilization rates resulted, but embryonic death occurred by day 4. Embryos residing in progesterone-treated does for up to 3 days survived normally when transferred to normal recipients, whereas day 4 embryos from treated does exhibited a reduced ability to implant. Uterine fluid (UF) protein pattern was examined on days 1 to 7 after mating. Total UF protein levels were significantly greater in treated animals on day 4 than in controls. Uteroglobin secretion was significantly advanced in the treated animals by day 3. Examination of the time of the arrival of embryos into the uterus revealed a delay in the progesterone-treated rabbits. This delay, coupled with the earlier secretion of uteroglobin in the treated rabbits, indicated a possible asynchrony of approximately 1 day between embryo arrival in the uterus and certain uterine proteins. To determine whether UF could be etiologically implicated in the progesterone-induced embryonic death, embryonic development in vitro and in vivo was examined after exposure to UF collected at different gestational stages. More normal day 3 morulae placed in UF from day 3 control and day 2 progesterone-treated rabbits developed than similar morulae placed in UF from day 2 controls and day 3 progesterone-treated does. Hence, partial physiologic synchrony was achieved. This was interpreted to mean that "asynchronous" UF can be embryotoxic. Infertility was transient. Ability of the does to produce young at a pregnancy immediately following a progesterone-treated pregnancy was not impaired.