Modification of pulsatile human chorionic gonadotrophin secretion in first trimester placental explants induced by polycyclic aromatic hydrocarbons.
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.
Barnea
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University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Camden.
Shurtz-Swirski
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D000096:Acetone / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D009924:Organ Culture Techniques; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011673:Pulsatile Flow / Q000187:drug effects; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D006063:Chorionic Gonadotropin; D004785:Environmental Pollutants; D017329:Triptorelin Pamoate; D000096:Acetone; D007987:Gonadotropin-Releasing Hormone; D001564:Benzo(a)pyrene; C019176:Tryptal