Résumé

P414

Consequences of metformin exposure on male mouse fertility

M. Faure*^a (Mlle), S. Alves^a (Mlle), C. Rouillon^a (Mlle), C. Rame^a (Mme), J. Dupont^a (Dr), P. Froment^a (Dr)

^a INRA, Nouzilly, FRANCE

* Melanie.Faure@tours.inra.fr

Metformin is a drug frequently used in the treatment of type 2 diabetes and disorders associated with insulin resistance. Some countries used it in the treatment of human gestational diabetes, which are risks for the mother and child. Few studies have examined the consequences on child of a metformin embryonic exposure. Results are limited to locomotors or neural effect, but no clear data could be obtained for reproductive organs analysis. Because of metformin crosses the human placenta, we have investigated, firstly, the effect of metformin administration during pregnancy in mice on male offspring. A reduction in testis size, seminiferous tubule size and in the number of Sertoli cells were noted at 1 day post-natal. But, we realized recently analysis of gonad function at puberty and adult stage. It appears that testes size were similar at 25dpn and 90dpn and the production of sperm and the velocity was not affected between control and treated group. However, spermatozoa present an increase in head abnormalities and the litter size, issue from the males exposed in utero, was reduced compared to control male. The concentration of testosterone was not altered in male exposed; however, adult males presented elevated LH in pituitary. Our second approach was to treat directly seminiferous tubule (Sertoli cells and germ cells) in vitro. Analysis of germ cells proportion by flow cytometry has not reported difference after metformin treatment. However, some studies have discussed potential effect of metformin on chromatin modification suggesting that analysis on epigenetics effects have to be performed.

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