Preconception Alcohol Increases Offspring Vulnerability to Stress.
The effect of preconception drinking by the mother on the life-long health outcomes of her children is not known, and therefore, in this study using an animal model, we determined the impact of preconception alcohol drinking of the mother on offspring stress response during adulthood. In our preconception alcohol exposure model, adult female rats were fed with 6.7% alcohol in their diet for 4 weeks, went without alcohol for 3 weeks and were bred to generate male and female offspring. Preconception alcohol-exposed offsprings' birth weight, body growth, stress response, anxiety-like behaviors, and changes in stress regulatory gene and protein hormone levels were evaluated. In addition, roles of epigenetic mechanisms in preconception alcohol effects were determined. Alcohol feeding three weeks prior to conception significantly affected pregnancy outcomes of female rats, with respect to delivery period and birth weight of offspring, without affecting maternal care behaviors. Preconception alcohol negatively affected offspring adult health, producing an increased stress hormone response to an immune challenge. In addition, preconception alcohol was associated with changes in expression and methylation profiles of stress regulatory genes in various brain areas. These changes in stress regulatory genes were normalized following treatment with a DNA methylation blocker during the postnatal period. These data highlight the novel possibility that preconception alcohol affects the inheritance of stress-related diseases possibly by epigenetic mechanisms.
The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.|Endocrinology and Animal Biosciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Shaima
S
Jabbar
The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Lucy G
LG
Chastain
The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Omkaram
O
Gangisetty
The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.|Endocrinology and Animal Biosciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Miguel A
MA
Cabrera
The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Kamil
K
Sochacki
The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Dipak K
DK
Sarkar
D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D008425:Maternal Behavior / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000209:etiology*
D002492:Central Nervous System Depressants; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D018161:Receptors, Mineralocorticoid; D012269:Ribosomal Proteins; C050482:Rpl19 protein, rat; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone