Paternal genetic contribution influences fetal vulnerability to maternal alcohol consumption in a rat model of fetal alcohol spectrum disorder.
BACKGROUND
Fetal alcohol exposure causes in the offspring a collection of permanent physiological and neuropsychological deficits collectively termed Fetal Alcohol Spectrum Disorder (FASD). The timing and amount of exposure cannot fully explain the substantial variability among affected individuals, pointing to genetic influences that mediate fetal vulnerability. However, the aspects of vulnerability that depend on the mother, the father, or both, are not known.


RESULTS
Using the outbred Sprague-Dawley (SD) and inbred Brown Norway (BN) rat strains as well as their reciprocal crosses, we administered ethanol (E), pair-fed (PF), or control (C) diets to the pregnant dams. The dams' plasma levels of free thyroxine (fT4), triiodothyronine (T3), free T3 (fT3), and thyroid stimulating hormone (TSH) were measured to elucidate potential differences in maternal thyroid hormonal environment, which affects specific aspects of FASD. We then compared alcohol-exposed, pair fed, and control offspring of each fetal strain on gestational day 21 (G21) to identify maternal and paternal genetic effects on bodyweight and placental weight of male and female fetuses.


CONCLUSIONS
SD and BN dams exhibited different baseline hypothalamic-pituitary-thyroid function. Moreover, the thyroid function of SD dams was more severely affected by alcohol consumption while that of BN dams was relatively resistant. This novel finding suggests that genetic differences in maternal thyroid function are one source of maternal genetic effects on fetal vulnerability to FASD. The fetal vulnerability to decreased bodyweight after alcohol exposure depended on the genetic contribution of both parents, not only maternal contribution as previously thought. In contrast, the effect of maternal alcohol consumption on placental weight was consistent and not strain-dependent. Interestingly, placental weight in fetuses with different paternal genetic contributions exhibited opposite responses to caloric restriction (pair feeding). In summary, these novel findings demonstrate both maternal and paternal genetic contributions to in utero vulnerability to alcohol, refining our understanding of the genetically-based heterogeneity seen in human FASD.
Sittig
Laura J
LJ
Asher Center, Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Redei
Eva E
EE
D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005220:Fathers; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000235:genetics; D005333:Fetus; D020022:Genetic Predisposition to Disease; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D018811:Maternal Exposure; D009035:Mothers; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000097:blood
D013963:Thyroid Hormones
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