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Cited by 35Effects and risks of endocrine disrupting chemicalsHypothalamic control of reproductive hormonesSexual Differentiation and Disorders

Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus

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Topper, Viktoria Y., Walker, Deena M., Gore, Andrea C.·2015·Molecular and Cellular Endocrinology
DOI 10.1016/j.mce.2015.07.013PMC PMC4553128
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Abstract

This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner.

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  • PCBs have been associated with global DNA hypomethylation and altered microRNA expression, particularly in the developing brain.

    “PCBs have been associated with global DNA hypomethylation and altered microRNA expression, particularly in the developing brain.”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Topper et al., 2015

    The Conclusions and implications section (page not provided) reports that gestational exposure to the PCB mixture A1221 altered microRNA expression in the developing rat hypothalamus. The paper does not report global DNA hypomethylation caused by PCBs; the hypomethylation study listed in its References concerns bisphenol A instead. (LLM, conf=0.90)

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  • Age- and sex-specific changes in microRNA expression have been described in the developing hypothalamus of rats, suggesting PCB exposure may reprogram neuroendocrine and synaptic development through long-lasting gene-regulatory mechanisms.

    “Age- and sex-specific changes in microRNA expression have also been described in the developing hypothalamus of rats, suggesting that PCB exposure may reprogram neuroendocrine and synaptic development through long-lasting gene-regulatory mechanisms (Dickerson et al., 2011; Topper et al., 2015).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Topper et al., 2015

    The Discussion and Conclusions report age- and sex-specific effects of gestational PCB exposure on microRNA expression in the rat hypothalamus, including an effect in adult males at P90. They do not establish that these changes reprogram synaptic development or act through lasting changes in target-gene expression; the paper reports few treatment-related changes in the measured target mRNAs. The supplied passages have section labels but no page numbers. (LLM, conf=0.86)

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Authors
Topper, V. Y., Walker, D. M., & Gore, A. C.
Affiliations
The University of Texas at Austin (US)
Corresponding author
Gore, Andrea C.
ORCID
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2015-10
Volume
414
Pages
42-52
ISSN
0303-7207 (ISSN-L)
DOI
10.1016/j.mce.2015.07.013
PMC
PMC4553128
OpenAlex
W928581375
Cited by
35
References
10
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 1
FWCI
2.30
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01es020662-05)
  • National Institute on Aging (F31AG034813)
  • National Institute of Environmental Health Sciences (R01-ES020662, R01ES023254)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
endocrine disruptors, microRNA expression, hypothalamus, sexual dimorphism, prenatal exposure, polychlorinated biphenyls, estradiol benzoate, medial preoptic nucleus, ventromedial hypothalamus, brain development, rat offspring
MeSH terms
Animals, Animals, Newborn, Environmental Pollutants, Estradiol, Female, Male, Polychlorinated Biphenyls, Pregnancy, Preoptic Area, RNA, Messenger, Sex Characteristics, Ventromedial Hypothalamic Nucleus, Gene Expression Regulation, Developmental, MicroRNAs, Rats

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