The relative transfer of estrogens and their glucuronides across the placenta in the guinea pig.

It has been suggested that estrogens can pass through the placenta because of their low molecular weight. This is supported by the demonstration of estriol in the urine of newborn male infants (1). However, there is no direct evidence to support the statment, nor is there information as to the nature of the estrogens that can or cannot be transferred. Estrogens, in common with other steroids, are rapidly conjugated in vivo with glucuronic acid. This converts them into water-soluble materials, in which form they are excreted in the urine. The unconjugated estrogens appear in the urine in only trace amounts. We have used C14 labeled estradiol and estriol in pregnant guinea pigs, and studied the relative permeability of the placenta to the unconjugated estrogens, as well as their conjugated forms, particularly the glucuronides. In the course of the investigation, it became obvious that the customary approach to the study of placental permeability may be misleading particularly when dealing with rapidly metabolized materials, unless the effects of fetal and maternal metabolism and of placental permeability are carefully differentiated. By using a technique which excludes fetal metabolism, clearly definable results were obtained. This was accomplished at hysterotomy by clamping the umbilical cord close to the fetus and perfusing the fetal side of the placenta.