The placenta and neurodevelopment: sex differences in prenatal vulnerability.
Prenatal insults, such as maternal stress, are associated with an increased neurodevelopmental disease risk and impact males significantly more than females, including increased rates of autism, mental retardation, stuttering, dyslexia, and attention deficit/hyperactivity disorder (ADHD). Sex differences in the placenta, which begin with sex chromosomes, are likely to produce sex-specific transplacental signals to the developing brain. Our studies and others have identified X-linked genes that are expressed at higher levels in the female placenta. Through a genome-wide screen after maternal stress in mice, we identified the X-linked gene O-linked N-acetylglucosamine transferase (OGT) and demonstrated its causality in neurodevelopmental programming producing a male-specific stress phenotype. Elucidating the sex-specific molecular mechanisms involved in transplacental signals that impact brain development is key to understanding the sex bias in neurodevelopmental disorders and is expected to yield novel insight into disease risk and resilience.
Department of Biomedical Sciences, School of Veterinary Medicine and Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Tracy L
TL
Bale
D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D065886:Neurodevelopmental Disorders / Q000209:etiology / Q000503:physiopathology*; D010920:Placenta / Q000502:physiology / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012727:Sex Characteristics; D013312:Stress, Physiological; D013315:Stress, Psychological
O-linked N-acetylgluosamine transferase; early prenatal stress; maternal stress; neurodevelopmental disorder; transplacental signal