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The placenta and neurodevelopment: sex differences in prenatal vulnerability
Open accessAbstract
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.
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“In many studies, male offspring appear to be the most strongly affected. Interestingly, they often present with what is known as a dysmasculinized phenotype (i.e., with behaviors and gene expression patterns most commonly seen in females) (Bale 2016).”
From Prenatal developmental origins of future psychopathology: mechanisms and pathways (2019) · cites this paper as Bale 2016
In the citing paper
“In one elegant model in mice based on the X-linked gene OGT (O-linked N-acetylglucosamine transferase), male placentas with typically lower levels of OGT are poised for epigenetic alterations that appear to produce robust transcriptional responses to maternal prenatal stress that result in increased stress sensitivity as adults (Bale 2016).”
From Prenatal developmental origins of future psychopathology: mechanisms and pathways (2019) · cites this paper as Bale 2016
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Metadata
- Authors
- Bale, T. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bale, Tracy L.
- ORCID
- Bale, Tracy L.
- Venue
- Dialogues in Clinical Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2016-12-31
- Volume
- 18
- Issue
- 4
- Pages
- 459-464
- ISSN
- 1294-8322 (ISSN-L)
- 1958-5969
- PMC
- PMC5286731
- OpenAlex
- W2988356887
- Cited by
- 236
- References
- 86
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 23 · 2023: 35 · 2022: 30 · 2021: 32 · 2020: 20 · 2019: 17 · 2018: 20 · 2017: 7
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Dialogues in Clinical Neuroscience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh091258-05)
- National Institute of Mental Health (P50MH099910, R37MH108286, R33MH104184, R01 MH-091258, R01MH087597)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- placenta, sex differences, brain development, prenatal stress, maternal stress, neurodevelopmental disorders, autism spectrum disorder, attention deficit hyperactivity disorder, X-linked genes, O-GlcNAc transferase, sex bias
- MeSH terms
- Animals, Female, Humans, Male, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics, Stress, Physiological, Stress, Psychological, Neurodevelopmental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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