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Cited by 28Effects and risks of endocrine disrupting chemicalsHypothalamic control of reproductive hormonesSexual Differentiation and Disorders

Maternal exposure to Dibutyl phthalate (DBP) or diethylstilbestrol (DES) leads to long-term changes in hypothalamic gene expression and sexual behavior

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Hunter, Damien, Heng, Kee, Mann, Navdeep, Anand-Ivell, Ravinder, Ivell, Richard·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22084163PMC PMC8073651
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Abstract

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8–12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.

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  • Perinatal exposure to DBP or DEHP alters sexual behavior and modifies hypothalamic gene expression in rats.

    “Perinatal exposure to DBP or DEHP also alters sexual behavior and modifies hypothalamic gene expression in rats (Hunter et al., 2021; Lee et al., 2006).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Hunter et al., 2021

    The Results (sections 2.4 and 2.5) report changes in hypothalamic gene expression and a significant increase in latency to mount after maternal DBP exposure in rats, although adult sexual behavior was otherwise little affected. This paper studied DBP and DES, not DEHP, so it does not support the DEHP portion of the citing sentence. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Hunter, D., Heng, K., Mann, N., Anand-Ivell, R., & Ivell, R.
Affiliations
  • The University of Adelaide (AU)
  • School of Biological Sciences, University of Adelaide, Adelaide 5005, Australia
Corresponding author
Ivell, Richard
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-04-17
Volume
22
Issue
8
Pages
4163
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22084163
PMC
PMC8073651
OpenAlex
W3155557124
Cited by
28
References
2
Citations by year
2026: 1 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 1
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Australian Research Council (DP 0773315)
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
dibutyl phthalate, diethylstilbestrol, hypothalamic gene expression, sexual behavior, endocrine disruption, oxytocin, kisspeptin, aromatase, estrogen receptor, gonadotropin-releasing hormone, anogenital distance, brain development, reproductive behavior, developmental programming
MeSH terms
Animals, Aromatase, Dibutyl Phthalate, Diethylstilbestrol, Estrogens, Non-Steroidal, Female, Hypothalamus, Gonadotropin-Releasing Hormone, Male, Oxytocin, Plasticizers, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Estrogen, Sexual Behavior, Animal, Vasopressins, Rats, Sprague-Dawley, Rats, Transcriptome, Kisspeptins

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