Maternal exposure to dibutyl phthalate (Dbp) or diethylstilbestrol (des) leads to long-term changes in hypothalamic gene expression and sexual behavior

Hunter, Damien; Heng, Kee; Mann, Navdeep; Anand-Ivell, Ravinder; Ivell, Richard

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.

• Journal Article Type: Article
• Acceptance Date: Apr 16, 2021
• Online Publication Date: Apr 17, 2021
• Publication Date: Apr 2, 2021
• Deposit Date: Jun 15, 2021
• Publicly Available Date: Jun 16, 2021
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 8
• Article Number: 4163
• Pages: 1-14
• DOI: https://doi.org/10.3390/ijms22084163
• Keywords: Physical and Theoretical Chemistry; Inorganic Chemistry; Organic Chemistry; Spectroscopy; Molecular Biology; Catalysis; General Medicine; Computer Science Applications
• Public URL: https://nottingham-repository.worktribe.com/output/5482724
• Publisher URL: https://www.mdpi.com/1422-0067/22/8/4163