A study coordinated by Inserm researchers at the Research Institute for Environmental and Occupational Health in Rennes shows that exposing pregnant mice to chlordecone affects the third generation of their male progeny. The number of germ cells – from which spermatozoa originate – decreases, their differentiation is affected, and there is also a decline in the number of mature spermatozoa. This research has been published in Scientific Reports.
During embryonic development, maternal exposure to certain environmental factors can have an impact on the unborn fetus. Early exposure to certain endocrine disruptors is suspected to lead to effects on reproductive function. The objective of this new study was to test, in animals, the consequences on multiple generations following gestational exposure to the known endocrine disruptor, chlordecone.
It has indeed been firmly established that exposure to high doses of chlordecone in adulthood has adverse effects on the production and quality of sperm in laboratory animals and in humans. Previous epidemiological studies conducted by Inserm in the French West Indies have shown that current levels of environmental exposure to chlordecone do not cause changes in sperm characteristics when exposed in adulthood. But given the ability of chlordecone to cross the placental barrier, the question of this substance having an effect during exposure in utero remained unanswered.
To address this question, pregnant mice were exposed by oral route to a daily dose of chlordecone which is not known to induce harmful effects in this species (100 μg per kg of bodyweight). The selected exposure period (from embryonic day 6 to 15) is not just a critical window for the transmission of epigenetic information to the next generations but also a vulnerable time when it comes to germ-cell development.
The principal findings?
Exposing the pregnant females to chlordecone affects the third generation of their male progeny (the first was not directly exposed): the number of germ cells – or spermatogonia – decreases, their differentiation is affected, and there is also a decline in the number of mature spermatozoa.
In other words, explains Fatima Smagulova, Inserm researcher and scientific manager of this study and an ATIP/Avenir team: “the entire germline in the male is affected, whether quantitatively or qualitatively, after two generations.
These modifications appear to be correlated to changes in the location of certain epigenetic marks (notably histone methylation and acetylation) situated in the promoters of genes coding for transcription factors, some of which are regulated by estrogen receptor 1 (ESR1).
Finally, modifications in the expression of 377 genes coding for proteins implicated in essential cell functions (chromosomal segregation, cell division and DNA repair) were observed.
This rodent study shows that prenatal exposure to chlordecone at low doses leads to transgenerational effects on sperm production and suggests that the hormone properties of the compound could be implicated in the mechanisms behind these effects. However, the actual impact on the fertility of men living in the West Indies following prenatal exposure to chlordecone remains to be elucidated.
Chlordecone is an organochlorine insecticide which was used from 1973 to 1993 in plantations in the French West Indies to combat the banana weevil. Its continued presence in the environment is responsible for contaminating local foodstuffs, whether plant or animal, terrestrial or aquatic. The local populations – including pregnant women – are exposed, as shown by impregnation studies previously conducted by Inserm, with current exposures occurring mainly through the consumption of contaminated foods.
Unit 1085 "Research Institute for Environmental and Occupational Health" (Inserm/Université de Rennes, Université Antilles-Guyane, EHESP)
Atip-Avenir Program team: Meiosis, Epigenetics and Reproduction
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"Physiology and Pathophysiology of the Urogenital Tract" team
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Inserm Research Director
Team: "Exposure Assessment and Epidemiological Research on Environment, Reproduction and Development"
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Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
Aurore Gely-Pernot1, Chunxiang Hao2, Louis Legoff1, Luc Multigner1, Shereen Cynthia D’Cruz1, Christine Kervarrec1, Bernard Jégou1, Sergei Tevosian3 & Fatima Smagulova11University Rennes, EHESP, Inserm, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, Fance.
2College of Pharmacy, Linyi University, 276000, Linyi, China.
3University of Florida, Department of Physiological Sciences Box 100144, 1333 Center Drive, 32610, Gainesville, FL, USA.