Modification of pulsatile human chorionic gonadotrophin secretion in first trimester placental explants induced by polycyclic aromatic hydrocarbons

Abstract

The polycyclic aromatic hydrocarbons are major environmental pollutants. Benzo[a]pyrene and 3-methylcholanthrene are prominent members of this group of compounds. In the present study, we have examined the effect of these carcinogens/mutagens upon human chorionic gonadotrophin (HCG) secretion in the first trimester placenta in vitro. At 7-9 weeks in static cultures, exposure to 50 microM benzo[a]pyrene for 24 h increased beta-HCG secretion by placental explants. The effect after 6 h of incubation was less apparent. The effect of 5 microM benzo[a]pyrene at the two time points also was less significant than 50 microM benzo[a]pyrene. In explants exposed to 50 microM 3-methylcholanthrene, the effect on HCG secretion was also stimulatory. In superfusion of placental explants pretreated overnight with benzo[a]pyrene, there was a similar increase in the pattern of pulsatile beta-HCG secretion, as analysed by the area under the curve and the pulse amplitude, which was most evident at 24 h with the 50 microM dose. No significant effect on pulse frequency was noted. The effect of 50 microM 3-methylcholanthrene was also stimulatory. In order to determine the functional integrity of the explants treated with benzo[a]pyrene, the effect of 1 min pulses of 10(-10) gonadotrophin-releasing hormone (GnRH) analogue (a known HCG stimulator in superfusion) was tested, demonstrating that it increased beta-HCG secretion compared to controls. In addition, there was also an increase in whole HCG, as measured by the Tandem-R assay following exposure to benzo[a]pyrene. In conclusion, short-term exposure to carcinogens increases HCG secretion of placental explants in early pregnancy and this effect is maintained after removal of the xenobiotic.