Metformin exposure affects human and mouse fetal testicular cells
| Autor: | V. Rouiller-Fabre, René Habert, René Frydman, Nelly Frydman, Pauline Tartarin, Pascal Froment, D. Moison, Charlotte Lécureuil, Emmanuelle Guibert, Samantha Pozzi, Joëlle Dupont |
|---|---|
| Přispěvatelé: | Cellules Souches et Radiations (SCSR (U967 / UMR-E_008)), Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Centro Oncologico Modenese, Policlinico di Modena, Sciences Analytiques, Bioanalytiques, Diagnostic et Miniaturisation (SABDM), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Ministere de l'Enseignement Superieur et de la Recherche, Universite Paris Diderot-Paris 7, Commissariat à l'énergie atomique (CEA), Institut National de la Sante et de la Recherche Medicale (INSERM), Institut National de la Recherche Agronomique (INRA) and was a part of the national programme, FERTiNERGY, funded by the French National Research Agency, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
steroidogenesis endocrine system diseases Organogenesis Mice 0302 clinical medicine Pregnancy Testis Testosterone 0303 health sciences education.field_of_study 030219 obstetrics & reproductive medicine Leydig cell Rehabilitation Obstetrics and Gynecology Gene Expression Regulation Developmental Organ Size Polycystic ovary 3. Good health Metformin Gestational diabetes medicine.anatomical_structure Prenatal Exposure Delayed Effects Female medicine.drug medicine.medical_specialty Population Mice Inbred Strains Biology [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction 03 medical and health sciences Insulin resistance Organ Culture Techniques Internal medicine medicine Animals Humans Hypoglycemic Agents RNA Messenger education 030304 developmental biology Cell Proliferation Fetus medicine.disease Embryo Mammalian fetal testis Endocrinology Reproductive Medicine Animals Newborn metformin |
| Zdroj: | Human Reproduction Human Reproduction, Oxford University Press (OUP), 2012, 27 (11), pp.3304-3314. ⟨10.1093/humrep/des264⟩ Human Reproduction, 2012, 27 (11), pp.3304-3314. ⟨10.1093/humrep/des264⟩ |
| ISSN: | 0268-1161 1460-2350 |
| DOI: | 10.1093/humrep/des264⟩ |
| Popis: | background: Metformin is a drug used in the treatment of diabetes and of some disorders related to insulin resistance, such as polycystic ovary syndrome. Gestational diabetes can cause complications for both mother and child, and some studies have shown a beneficial effect of metformin during pregnancy without an increase in perinatal complications. However, the effects on the gonads have not been properly studied. Here we investigated the effect of metformin administered during pregnancy on the development and function of the fetal testis. methods: A dual approach in vitro and in vivo using human and mouse models was chosen. Cultures of human and murine organotypic testes were made and in vivo embryonic testes were analysed after oral administration of metformin to pregnant mice. results: In human and mouse organotypic cultures in vitro, metformin decreased testosterone secretion and mRNA expression of the main factors involved in steroid production. In vitro, the lowest observed effect concentration (LOEC) on testosterone secretion was 50 mM in human, whereas it was 500 mM in mouse testis. Lactate secretion was increased in both human and mouse organotypic cultures with the same LOEC at 500 mM as observed in other cell culture models after metformin stimulation. In vivo administration of metformin to pregnant mice reduced the testicular size of the fetal and neonatal testes exposed to metformin during intrauterine life. Although the number of germ cells was not affected by the metformin treatment, the number of Sertoli cells, the nurse cells of germ cells, was slightly yet significantly reduced in both periods (fetal period: P ¼ 0.007; neonatal period: P ¼ 0.03). The Leydig cell population, which produces androgens, and the testosterone content were diminished only in the fetal period at 16 days post-coitum. conclusions: This study showed a potentially harmful effect of metformin treatment on the development of the fetal testis and should encourage future human epidemiological studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|