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Cited by 71Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersHypothalamic control of reproductive hormones

Effects of perinatal exposure to phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats

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LEE, Hwi-Cheul, YAMANOUCHI, Keitaro, NISHIHARA, Masugi·2006·Journal of Reproduction and Development
DOI 10.1262/jrd.17096
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Abstract

Our previous research has identified the granulin (grn) and p130 genes as sex steroid-regulated genes in the neonatal rat hypothalamus that might be involved in sexual differentiation of the brain. Since phthalate/adipate esters such as di-n-butyl phthalate (DBP), diisononyl phthalate (DINP), and di-2-ethylhexyl adipate (DEHA) are suspected to interfere with the endocrine system as environmental endocrine disruptors having estrogenic or antiandrogenic properties, these chemicals may affect sexual differentiation of the brain. The present study assessed the effects of perinatal exposure to DBP, DINP, and DEHA on grn and p130 mRNA expressions in the hypothalamus on postnatal day (PND) 7 and sexual behaviors after maturation in rats. Maternal rats were given a phytoestrogen-free diet containing different doses of DBP (20, 200, 2,000, and 10,000 ppm), DINP (40, 400, 4,000, and 20,000 ppm) and DEHA (480, 2,400, and 12,000 ppm) from gestational day 15 to the day of weaning (PND 21). DBP and DINP exposure during the perinatal period resulted in an increase in hypothalamic grn and p130 mRNA levels in females and males, respectively, but DEHA exposure decreased expression levels of grn in males and p130 in females, although the effects were not dose-dependent. After maturation, male rats that were exposed to several doses of DBP, DINP, and DEHA displayed decreased copulatory behavior. The lordosis quotient was decreased in females perinatally exposed to DBP, DINP, and DEHA at all the doses used. On the other hand, serum levels of LH and FSH in both sexes and the estrous cycles in females were not affected by the treatments. These results suggest that inappropriate expression of grn and/or p130 genes in the brains of male and female neonatal rats by perinatal exposure to these chemicals may exert permanent effects on the hypothalamus, thereby decreasing sexual behavior after maturation.

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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 Lee et al., 2006

    The Abstract and the sections on hypothalamic gene expression and sexual behavior report changes after perinatal DBP exposure. The paper studied DBP, DINP, and DEHA—not DEHP—so it does not support the DEHP part of the claim. Page numbers were not provided in our copy. (LLM, conf=0.91)

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Cited by

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Authors
LEE, H.-C., YAMANOUCHI, K., & NISHIHARA, M.
Affiliations
The University of Tokyo (JP)
ORCID
Venue
Journal of Reproduction and Development
Publisher
Japanese Society of Animal Reproduction
Published
2006
Volume
52
Issue
3
Pages
343-352
ISSN
  • 0916-8818 (ISSN-L)
  • 1348-4400
DOI
10.1262/jrd.17096
OpenAlex
W1983317914
Cited by
71
References
0
Citations by year
2026: 2 · 2025: 5 · 2024: 8 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 3 · 2015: 3 · 2014: 2 · 2012: 3
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Reproduction and Development (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
phthalates, dibutyl phthalate, diisononyl phthalate, di(2-ethylhexyl) adipate, endocrine disruptors, perinatal exposure, hypothalamus, granulin, sexual differentiation of the brain, sexual behavior, lordosis, mating behavior
MeSH terms
Progranulins, Adipates, Animals, Animals, Newborn, Environmental Exposure, Female, Gene Expression Regulation, Hypothalamus, Male, Nuclear Proteins, Phosphoproteins, Phthalic Acids, RNA, Messenger, Sexual Behavior, Animal, Intercellular Signaling Peptides and Proteins, Rats, Endocrine Disruptors

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