Gestational age dependent, rapid and delayed effect of epidermal growth factor upon human chorionic gonadotropin secretion by the first trimester explants

Abstract

EGF is believed to play an important role in the regulation of placental function. We have examined in detail, the effect of 50–200 ng/ml EGF on first trimester (7–13 gestational weeks) placental human chorionic gonadotropin (hCG) secretion using both static (explants and isolated cells) and kinetic (superfusion of explants) culture methods. In 7–9 week explants, short (1–4 minutes) pulses of EGF increased both the rate and amplitude of spontaneous hCG pulses. This effect was dose dependent and the concentration of 50 ng/ml was the most effective. Addition of 50 ng/ml EGF for 90 minutes in superfusion caused an initial increase followed by a significant decrease in spontaneous pulsatile hCG secretion. hCG secretion was not affected by a subsequent addition of a one minute pulse of 50 ng/ml EGF, reflecting desensitization. A gestational age dependent delayed effect of EGF wsas documented. At 7–9 weeks, following overnight preincubation with 50 ng/ml EGF, there was a significant increase in hCG pulse parameters as calculated by PULSAR. In contrast, at >10 weeks, the growth factor effect was inhibitory. In explants cultured for 24 hours, the same trend was noted at 7–9 weeks. EGF caused a two-fold increase while >11 week, the effect was markedly inhibitory. In isolated trophoblastic cell cultures, EGF added daily for the first week increase in hCG secretion until the fifth day. However, apparently no morphological changes were associated with this increase. In conclusion, EGF has a gestational dependent rapid, long term, and delayed effect on hCG secretion in the first trimester. The involvement of EGF in control of hCG secretion is strongly suggested.