Studies on the embryopathic effects of ethanolamine in Long-Evans rats: preferential embryopathy in pups contiguous with male siblings in utero.

The embryopathic effects of high doses of ethanolamine were evaluated in pregnant Long-Evans rats during the "critical period" or organogenesis. Ethanolamine was given by gavage at levels of 0, 500, 300, or 50 mg/kg/day (24%, 14.4%, or 2.4% of the LD50 value). Ethanolamine caused dose-dependent increases in intrauterine deaths, malformations, and intrauterine growth retardation. Embryolethality caused by 500 mg/kg of ethanolamine was not random: male pups contiguous to two male siblings (designated mMm) were almost quantitatively replaced by resorptions that were contiguous to two live male pups (designated mRm) (mMm pups constituted 6.7% of control implants and decreased to only 0.9% of group II implants while mRm resorptions increased from 0.3% in controls to 5.6% in group II dams). Intrauterine growth retardation and increases in gross structural anomalies (considered indicative of depressed fetal growth) more severely affected male than female offspring at all dose levels. Pups of either sex who were contiguous to male siblings were more adversely affected than those offspring contiguous to one or more female siblings. As ethanolamine was given prior to the period of greatest fetal growth and fetal sex steroidogenesis, it is suggested that intrauterine levels of female sex steroids (estradiol) enhance fetal repair of cellular damage while testosterone inhibits fetal repair or exacerbates previous embryonic damage by some unknown mechanism. Such interaction furthers the concept that intrauterine position affects the endpoints of developmental toxicity, as expressed at parturition.