In pregnant mares during late gestation, little, if any, progesterone (P 4 ) is found in the maternal circulation. Hence, quiescence of the equine uterus is believed to be maintained by metabolites of pregnenolone and P 4 known as progestagens, which are produced by the uteroplacental tissues. However, little is known about the ontogeny, distribution, or actual rates of uteroplacental progestagen production in pregnant mares and their fetuses during the second half of pregnancy. Therefore, the present study measured the rates of uteroplacental uptake and output of eight specific progestagens in chronically catheterized, pregnant pony mares from 180 days to term. No significant uteroplacental uptake of any of the eight individual progestagens was observed from the uterine circulation. In contrast, significant uteroplacental uptake was observed for five of the eight individual progestagens from the umbilical circulation, and the uptakes increased toward term. The major uteroplacental progestagen outputs were 5␣-pregnane-3,20-dione (5␣DHP) and 20␣-hydroxy-5␣-pregnan-3-one (20␣5P). These were released into both the umbilical and uterine circulations at rates that increased toward term. The majority of the total uteroplacental 20␣5P output was distributed into the uterine circulation at all gestational ages studied. In contrast, distribution of the total uteroplacental 5␣DHP output switched from preferential delivery into the uterine circulation before 220 days of gestation to release predominantly into the umbilical circulation after 260 days. These findings demonstrate that uteroplacental progestagen production changes during the second half of gestation, which may have important implications for the maintenance of pregnancy and the onset of labor in the mare. placenta, pregnancy, progesterone, steroid hormones

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Summary Maternal plasma progestagen concentrations increase about 20 days before parturition. The major contributors to the increase are reduced metabolites (ie 5α‐pregnanes). Precocious increases (ie < 310 days of gestation) in these metabolites may occur in abnormal pregnancies. The effects of CRH, ACTH or betamethasone administered to the foetus at gestational ages ranging from about 250 to 320 days were examined. Sixteen healthy pony mares were used for foetal injection employing aseptic techniques. Water or normal saline were used as controls. Maternal plasma progestagen concentrations were measured using a commercial radioimmunoassay (RIA) progesterone kit and results were confirmed using gas chromatography‐mass spectrometry (GC‐MS). Results demonstrated clearly that an increase in maternal plasma progestagen concentrations occurred after injection of ACTH, CRH or betamethasone to the foetus, irrespective of gestational age. A comparable increase was not observed in the control animals. Of the 16 mares in which the foetus was injected, 13 produced viable foals at gestational ages ranging from 307 to 339 days whereas 3 mares delivered non‐viable foals at 284 to 306 days gestation. The results support the hypothesis that the pre‐parturient rise in progestagens occurring in the mare is the result of foetal adrenocortical activity.

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