The distribution of placental oxidoreductase isoforms provides different milieus of steroids influencing pregnancy in the maternal and fetal compartment

Abstract

Using information based on the steroid metabolome in maternal and fetal body fluids, we attempted to ascertain whether there is a common mechanism, which is based on the placental distribution of various isoforms of 17β-hydroxysteroid dehydrogenases and aldo-keto reductases. This system simultaneously provides a higher proportion of active progestogens in fetal circulation and a higher proportion of active estrogens and GABAergic steroids in the maternal compartment. The data obtained using gas chromatography-mass spectrometry completely support the aforementioned hypothesis. We confirmed a common trend to higher ratios of steroids with hydroxy-groups in the 3α-, 17β-, and 20α-positions to the corresponding 3-oxo-, 17-oxo-, and 20-oxo-metabolites, respectively, in the maternal blood when compared with the fetal circulation, and the same tendency was obvious in the 3α-hydroxy/3β-hydroxy steroid ratios. A decreasing trend was observed in the ratios of active estrogens and neuro-inhibitory steroids to their inactive counterparts in fetal and maternal body fluids. This was probably associated with a limited capacity of placental oxidoreductases in the converting of estrone to estradiol during the transplacental passage. Although we observed a decreasing trend in pregnancy-sustaining steroids with increasing gestational age, we recorded rising levels of estradiol and particularly of estriol, regardless of the limited capacity of placental oxidoreductases. Besides the estradiol, which is generally known as an active estrogen, estriol may be of importance for the termination of pregnancy with respect to its excessive concentrations near term which allows its binding to estrogen receptors.