ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2022) 19 7.13 | DOI: 10.1530/ey.19.7.13

ESPEYB19 7. Puberty Basic Science (7 abstracts)

7.13. Multi- and transgenerational outcomes of an exposure to a mixture of endocrine-disrupting chemicals (EDCs) on puberty and maternal behavior in the female rat

López-Rodríguez D , Aylwin CF , Delli V , Sevrin E , Campanile M , Martin M , Franssen D , Gérard A , Blacher S , Tirelli E , Noël A , Lomniczi A & Parent AS



Environ Health Perspect.2021 Aug;129(8):87003. doi: 10.1289/EHP8795. Epub 2021 Aug 12. PMID: 34383603. https://ehp.niehs.nih.gov/doi/10.1289/EHP8795?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Brief Summary: Using a rodent model of exposure to a mixture of endocrine disrupting chemicals (EDCs), the authors identified transgenerational disruption of sexual maturation via hypothalamic epigenetic reprogramming.

The secular trend in the onset of puberty appears to be explained at least in part by exogenous environmental factors [1]. Among them, EDCs have been largely reported to affect sexual maturation in rodents [2] by targeting its central hypothalamic regulation [3]. However, the consequences of EDC exposure on puberty across generations have been much less investigated.

These authors used a mixture of 13 estrogenic or anti-androgenic EDCs at doses relevant to human exposure [4]. Ancestral exposure to the mixture delayed pubertal onset and altered folliculogenesis and estrous cyclicity in F2 and F3 generations. The pubertal delay found in F3 EDC exposed females was associated with a delayed maturation of GnRH secretion and involved epigenetic reprogramming of key hypothalamic genes involved in the control of puberty such as Kiss1. In addition, F1 to F3 maternal behavior was impaired and associated with a loss in hypothalamic dopaminergic signaling. As altered maternal behavior is known to affect pubertal timing of the descendants [5], the authors used a cross-fostering model and demonstrated that maternal phenotype was recovered in EDC-exposed pups raised by unexposed dams, while puberty was still delayed.

Overall, this study showed that rats developmentally exposed to an EDC mixture exhibited multi- and transgenerational disruption of sexual maturation and maternal care via hypothalamic epigenetic reprogramming. These results raise concerns about the impact of environmentally relevant EDC mixtures on future generations

References: 1. Parent AS, Franssen D, Fudvoye J, Gérard A, Bourguignon JP. (2015) “Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents.” Front Neuroendocrinol.; 38:12–36. 2. Bourguignon JP, Juul A, Franssen D, Fudvoye J, Pinson A, Parent AS. (2016) “Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects: The Case Study of Pubertal Timing.” Horm Res Paediatr.; 86(4):221–232. 3. Lopez-Rodriguez D, Franssen D, Bakker J, Lomniczi A, Parent AS. (2021) “Cellular and molecular features of EDC exposure: consequences for the GnRH network.” Nat Rev Endocrinol.; 17(2):83–96. 4. Christiansen S, Kortenkamp A, Axelstad M, Boberg J, Scholze M, Jacobsen PR, Faust M, Lichtensteiger W, Schlumpf M, Burdorf A, Hass U. (2012) “Mixtures of endocrine disrupting contaminants modelled on human high end exposures: an exploratory study in rats.” Int J Androl.; 35(3):303–16. 5. Cameron N, Del Corpo A, Diorio J, McAllister K, Sharma S, Meaney MJ. (2008) “Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat.” PLoSOne; 3(5): e2210.

Article tools

My recent searches

No recent searches.