Pregnancy: Gestational-age-dependent effects of retinoids on HCG secretion by placental explants

Vitamin A (VITA) is considered to be an essential nutrient inboth pregnant and non-pregnant states. It has been suggestedthat VITA, among others, is involved in the process of morphogenesis.In contrast, synthetic derivatives of VITA, specifically Tigasone(etretinate, TIG) and Roaccutane (isotretinoin, ROA), are regardedas major teratogens. Therefore, in the present study we haveexamined the effect of VITA and other retinoids on human chorionicgonado-trophin (HCG) secretion by placental explants in thefirst trimester. Results show that, at 7–9 gestationalweeks, all three compounds had a significant inhibitory effecton HCG secretion. In the case of VITA, this inhibition was time-dependent.A biphasic maximal inhibition was present at 1 µM concentrationswhen the retinoids VITA, TIG and ROA were added for 16 h (52,58 and 57%, respectively; P < 0.01 by one-way analysis ofvariance). In contrast, the addition of the three retinoidsat 1 µM concentrations for 16 h had no significant effecton HCG secretion by placental explants of 11–13 weeksgestational age. In conclusion, both natural and synthetic retinoidsdemonstrate a significant inhibitory effect on HCG secretionby the early placenta (pre-HCG peak). VITA may be involved incausing a plateau and the later decline in HCG secretion. Inhibitionof HCG secretion by retinoids may contribute either directlyor indirectly to their teratogenicity.