Pitetti Jean-Luc, Calvel Pierre, Zimmermann Céline, Conne Béatrice, Papaioannou Marilena D, Aubry Florence, Cederroth Christopher R, Urner Françoise, Fumel Betty, Crausaz Michel, Docquier Mylène, Herrera Pedro Luis, Pralong François, Germond Marc, Guillou Florian, Jégou Bernard, Nef Serge
Department of Genetic Medicine and Development, National Center of Competence in Research, Frontiers in Genetics, University of Geneva, 1211 Geneva 4, Switzerland.
Mol Endocrinol. 2013 May;27(5):814-27. doi: 10.1210/me.2012-1258. Epub 2013 Mar 21.
Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.
睾丸大小和精子生成与成年支持细胞（SCs）的总数直接相关。尽管建立足够数量的支持细胞对未来男性生育能力至关重要，但调节支持细胞存活、增殖和成熟的因素的鉴定和表征仍不完整。为了研究胰岛素样生长因子（IGF）系统是否是生殖细胞（GCs）和支持细胞发育及功能所必需的，我们在生殖细胞系或支持细胞中特异性地使胰岛素受体（Insr）、IGF1受体（Igf1r）或两者失活。虽然胰岛素/IGF信号的缺失似乎对生殖细胞和精子发生并非必需，但在支持细胞中同时缺乏Insr和Igf1r的成年小鼠睾丸（SC-Insr;Igf1r），由于在胎儿晚期和新生儿早期睾丸期未成熟支持细胞的增殖率降低，睾丸大小和每日精子产量减少了75%。此外，体内分析表明，促卵泡激素（FSH）需要胰岛素/IGF信号通路来介导其对未成熟支持细胞的增殖作用。总体而言，这些结果强调了胰岛素家族生长因子在调节支持细胞最终数量、睾丸大小和每日精子产量方面所起的重要作用。它们还表明，胰岛素/IGF信号通路是FSH介导的支持细胞增殖所必需的。
