GESTATIONAL-AGE-DEPENDENT EFFECTS OF RETINOIDS ON HCG SECRETION BY PLACENTAL EXPLANTS

Vitamin A (VITA) is considered to be an essential nutrient in both pre gnant and non-pregnant states. It has been suggested that VITA, among others, is involved in the process of morphogenesis. In contrast, synt hetic derivatives of VITA, specifically Tigasone (etretinate, TIG) and Roaccutane (isotretinoin, ROA), are regarded as major teratogens. The refore, in the present study we have examined the effect of VITA and o ther retinoids on human chorionic gonadotrophin (HCG) secretion by pla cental explants in the first trimester. Results show that, at 7-9 gest ational weeks, all three compounds had a significant inhibitory effect on HCG secretion. In the case of VITA, this inhibition was time-depen dent. A biphasic maximal inhibition was present at 1 mu M concentratio ns when the retinoids VITA, TIG and ROA were added for 16 h (52, 58 an d 57%, respectively; P < 0.01 by one-way analysis of variance). In con trast, the addition of the three retinoids at 1 mu M concentrations fo r 16 h had no significant effect on HCG secretion by placental explant s of 11-13 weeks gestational age. In conclusion, both natural and synt hetic retinoids demonstrate a significant inhibitory effect on HCG sec retion by the early placenta (pre-HCG peak). VITA may be involved in c ausing a plateau and the later decline in HCG secretion. Inhibition of HCG secretion by retinoids may contribute either directly or indirect ly to their teratogenicity.