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

Vitamin A (VITA) is considered to be an essential nutrient in both pregnant and non-pregnant states. It has been suggested that 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 regarded as major teratogens. Therefore, in the present study we have examined the effect of VITA and other retinoids on human chorionic gonadotrophin (HCG) secretion by placental explants in the first trimester. Results show that, at 7-9 gestational weeks, all three compounds had a significant inhibitory effect on HCG secretion. In the case of VITA, this inhibition was time-dependent. A biphasic maximal inhibition was present at 1 microM concentrations when the retinoids VITA, TIG and ROA were added for 16 h (52, 58 and 57%, respectively; P < 0.01 by one-way analysis of variance). In contrast, the addition of the three retinoids at 1 microM concentrations for 16 h had no significant effect on HCG secretion by placental explants of 11-13 weeks gestational age. In conclusion, both natural and synthetic retinoids demonstrate a significant inhibitory effect on HCG secretion by the early placenta (pre-HCG peak). VITA may be involved in causing a plateau and the later decline in HCG secretion. Inhibition of HCG secretion by retinoids may contribute either directly or indirectly to their teratogenicity.