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Effets d’une exposition à la Vinclozoline et à la Génistéine de la gestation à l’âge adulte sur la fonction de reproduction du ratWistar mâle: protocole et résultats préliminaires

Reproductive effects of chronic exposure (from conception to adulthood) to low concentrations of genistein and vinclozolin in male Wistar rats: protocol and preliminary results

Andrologie volume 13, pages 170–178 (2003)Cite this article

Resume

Les perturbateurs endocriniens (EDs) présents dans l’environnement sont de plus en plus mis en cause pour expliquer les modifications de la fonction de reproduction mâle, y compris chez l’homme. Cependant, leurs mécanismes d’action sur la fonction de reproduction sont peu connus et le lien de causalité chez l’homme n’est pas démontré. Parmi les nombreuses études expérimentales rapportées, les conditions d’exposition sont le plus souvent très éloignées de la situation environnementale (doses élevées, courtes périodes d’expositon, une seule molécule). Le but de ce projet est d’étudier les effets d’une exposition à deux EDs isolés et associés: la génistéine, phyto-oestrogène et la vinclozoline, fongicide à activité antiandrogénique sur la fonction de reproduction du ratWistar mâle. Pour chaque molécule, 2 doses ont été choisies: une dose élevée et une dose faible compatible avec des expositions environnementales, avec une administration par gavage de la conception à l’âge adulte. Le protocole prévoyait le sacrifice d’une partie des ratons au sevrage et des rats adultes après accouplement, et les examens suivants: pesée des animaux et des organes, réserves spermatiques, histologie des organes de la reproduction et dosage des hormones sexuelles. De plus, une identification plus fine des effets reposera sur la morphométrie testiculaire, l’évaluation de la qualité nucléaire, du mouvement et du degré de fragmentation de l’ADN des spermatozoïdes. A la recherche des mécanismes possiblement en cause, il est prévu d’analyser les récepteurs hormonaux aux oestrogènes, androgènes, progestérone et FSH et d’étudier des modifications de l’apoptose des cellules germinales.

L’élevage des animaux a pu être mené à bien et les premiers résultats ont été:

  1. 1.

    la mise en évidence d’anomalies du développement testiculaire, des vésicules séminales, des épididymes et du pénis observées après exposition à de faible dose pour les composés testés et/ou leur combinaison;

  2. 2.

    une diminution de la mobilité progressive et d’autres paramètres cinétiques observée dès les faibles doses pour les molécules isolées ou associées;

  3. 3.

    une diminution des capacités de reproduction, surtout pour les mâles exposés à la faible dose de vinclozoline et à la combinaison avec la génistéine.

Ces résultats originaux nous incitent maintenant à préciser les effets au niveau tissulaire et cellulaire et à étudier certains des mécanismes possiblement en cause.

Abstract

Current evidence indicates that endocrine disrupters (EDs) can induce adverse effects on the male reproductive tract in various mammalian species. Recent reports indicate deterioration in male reproductive health in several human populations, but the evidence for a causal link with endocrine disruption is still weak. In addition, the experimental conditions of most of the reportedin vivo studies are not representative of environmental exposures (for example, high doses, short-term exposure, a single ED) and the mechanisms by which EDs disrupt the reproductive system are poorly understood. The objective of the present study is to develop an animal model to assess the reproductive effects and study the putative cellular and molecular mechanisms involved after exposure to genistein (phytoestrogen) and vinclozolin (fungicide with a known antiandrogenic potential) alone or in combination. The study will be performed in male Wistar rats, with administration of low and high doses of the compounds from conception to adulthood and a subset of the males in each treatment group will be mated with unexposed females. We plan to assess the level of sperm production, histology of the reproductive organs, motility and morphometry of spermatozoa and hormone levels, as well as DNA fragmentation of spermatozoa and determination of the number of germ cells, Sertoli cells and the diameters of seminiferous tubules. Estrogen, androgen, progesterone and FSH receptors will be detected and quantified and the level of testicular apoptosis and several apoptosis pathways will be studied to determine the putative cellular and molecular mechanisms involved. The preliminary results confirmed the developmental effects previously reported for high doses of vinclozolin. More interestingly, they indicated a number of deleterious effects for male rats exposed to low dosages alone or mixtures of low and high dosages compared to controls and rats exposed to high dosages alone. For example, a number of developmental anomalies of the genitalia were observed and a significant decrease of sperm motility and motion and fertilizing ability were observed. These preliminary results provide evidence that chronic exposure to environmental levels of EDs or mixtures of EDs have a detrimental impact on the male reproductive tract. The next step involves assessment of the anatomical disorders and the study of some of the cellular and molecular mechanisms possibly involved.

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Authors and Affiliations

  1. Service d’Histologie-Embryologie, Biologie de la Reproduction, Groupe d’Etude de la Fertilité de la Fertilité Humaine (GREFH), Université Paris V et Hôpital Cochin, Paris

    Florence Eustache, Corinne Lesaffre, Pierre Jouannet & Jacques Auger

  2. INRA, UMR de Toxicologie Alimentaire, Dijon

    Marie Chantal Cannivenc

  3. INRA, UMR 1089 Xénobiotiques, Toulouse

    Jean Pierre Cravedi

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  1. Florence Eustache
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  2. Corinne Lesaffre
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  3. Marie Chantal Cannivenc
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Correspondence to Florence Eustache.

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Eustache, F., Lesaffre, C., Cannivenc, M.C. et al. Effets d’une exposition à la Vinclozoline et à la Génistéine de la gestation à l’âge adulte sur la fonction de reproduction du ratWistar mâle: protocole et résultats préliminaires. Androl. 13, 170–178 (2003). https://doi.org/10.1007/BF03034432

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  • DOI: https://doi.org/10.1007/BF03034432

Mots clés

  • perturbateurs endocriniens
  • faible dose
  • association
  • appareil génital mâle
  • fertilité
  • spermatozoïdes

Key-Words

  • endocrine disrupters
  • low dosage
  • mixtures
  • male fertility
  • reproductive tract
  • spermatozoa

Basic and Clinical Andrology

ISSN: 2051-4190