Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior

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 als...

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Main Authors: Damien Hunter, Kee Heng, Navdeep Mann, Ravinder Anand-Ivell, Richard Ivell
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/8/4163
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author Damien Hunter
Kee Heng
Navdeep Mann
Ravinder Anand-Ivell
Richard Ivell
author_facet Damien Hunter
Kee Heng
Navdeep Mann
Ravinder Anand-Ivell
Richard Ivell
author_sort Damien Hunter
collection DOAJ
description 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 (<i>n</i> = 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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spelling doaj.art-b12f6c36b95147d986733c8c863013082023-11-21T15:59:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228416310.3390/ijms22084163Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual BehaviorDamien Hunter0Kee Heng1Navdeep Mann2Ravinder Anand-Ivell3Richard Ivell4School of Biological Sciences, University of Adelaide, Adelaide 5005, AustraliaSchool of Biological Sciences, University of Adelaide, Adelaide 5005, AustraliaSchool of Biological Sciences, University of Adelaide, Adelaide 5005, AustraliaSchool of Biological Sciences, University of Adelaide, Adelaide 5005, AustraliaSchool of Biological Sciences, University of Adelaide, Adelaide 5005, AustraliaXenobiotic 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 (<i>n</i> = 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.https://www.mdpi.com/1422-0067/22/8/4163hypothalamusendocrine disruptionsexual behavioroxytocinkisspeptin
spellingShingle Damien Hunter
Kee Heng
Navdeep Mann
Ravinder Anand-Ivell
Richard Ivell
Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior
International Journal of Molecular Sciences
hypothalamus
endocrine disruption
sexual behavior
oxytocin
kisspeptin
title Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior
title_full Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior
title_fullStr Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior
title_full_unstemmed Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior
title_short Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior
title_sort maternal exposure to dibutyl phthalate dbp or diethylstilbestrol des leads to long term changes in hypothalamic gene expression and sexual behavior
topic hypothalamus
endocrine disruption
sexual behavior
oxytocin
kisspeptin
url https://www.mdpi.com/1422-0067/22/8/4163
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