Changes in the reproductive system following acute prenatal exposure to ethanol or methylazoxymethanol in the rat: I. Effects on immunoreactive LHRH cell number.
It has long been recognized that ethanol (EtOH) interferes with the hypothalamo-pituitary-gonad axis in adults of many species, and recent studies have provided evidence for similar effects after prenatal EtOH exposure. Since EtOH is capable of injuring dividing cells, we investigated the possibility that a single acute in utero EtOH exposure during the period of LHRH neuron formation might change the number of immunoreactive LHRH cells in the hypothalamus. Final LHRH cell division in Long-Evans rats was determined by [3H]thymidine autoradiography to take place over a short period between gestation days 12 and 13. Subsequently, pregnant rats were treated acutely with either EtOH or methylazoxymethanol (MAM), a known neuroteratogen, and the numbers of immunoreactive LHRH cells were counted. On gestation day 22, LHRH-positive cell numbers were significantly fewer than control numbers in both EtOH- and MAM-exposed offspring. On postnatal day 60, cell numbers in EtOH-exposed offspring did not differ from control numbers, whereas cells in MAM-exposed offspring remained significantly reduced. In controls, there were 40% fewer LHRH-positive cells on postnatal day 4 than in late gestation or at maturity. We conclude that 1) acute exposure to a high dose of EtOH at a critical time in early gestation can alter the expression of LHRH in late gestation; 2) exposure to MAM in the same period alters LHRH expression before birth and in the adult; and 3) in the early postnatal period, LHRH expression decreases profoundly.
Gavin
C E
CE
Department of Obstetrics and Gynecology, University of Rochester, New York 14642.
Kates
B
B
Hoffman
G E
GE
Rodier
P M
PM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010865:Pilot Projects; D010902:Pituitary Gland / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D007987:Gonadotropin-Releasing Hormone; D000431:Ethanol; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol