Consequence of antidiabetic treatment in utero on male mouse fertility
M. Faure*a (Mlle), S. Alvesa (Mlle), C. Rouillona (Mlle), E. Jeanpierrea (M.), C. Raméa (Mme), J. Duponta (Dr), P. Fromenta (Dr)
a INRA, UMR85 Physiologie de la Reproduction et des Comportements/CNRS, UMR7247/Université François Rabelais de Tours/IFCE, Nouzilly, France, 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 as in the treatment of human gestational diabetes. Few studies have examined the consequences of a metformin embryonic exposure. Results are limited to locomotors or neural effects, but no clear data are available for reproductive organs. Because metformin cross the human placenta, we have investigated, the effect of a 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.
Recently, we analysed the gonad function at puberty and adult stage. It appears those males were less fertile despite a similar testes size and a production of sperm and the velocity that were not affected between control and treated group. However, the morphology of spermatozoa present some alteration and an increase in head abnormalities were observed. Moreover, analysis of spermatozoa by immunohistochemistry reported an increase in chromatin modification and change on epigenetic marks. The concentration of testosterone was not altered in male exposed; however, adult males exposed to metformin during fetal life presented elevated LH in pituitary. Male mice present also a metabolic dysregulation as suggested by a higher weight of adipose tissue, a reduction in adiponectin expression and a change in CPT1 expression in adipocytes.
In conclusion, consequences observed in testis function could be direct and indirect as suggested the development of metabolic disorders on male exposed at metformin in utero.
L’auteur n’a pas transmis de déclaration de conflit d’intérêt.