Tumor Suppressor PTEN Regulates Negatively Sertoli Cell Proliferation, Testis Size, and Sperm Production In Vivo
| العنوان: | Tumor Suppressor PTEN Regulates Negatively Sertoli Cell Proliferation, Testis Size, and Sperm Production In Vivo |
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| المؤلفون: | Françoise Kühne, Yasmine Neirijnck, Pauline Sararols, Serge Nef, Michelangelo Foti, Nina Atanassova, Chloé Mayère, Ekaterina Pavlova |
| المصدر: | Endocrinology, Vol. 160, No 2 (2019) pp. 387-398 |
| بيانات النشر: | The Endocrine Society, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Sertoli cell proliferation, 030209 endocrinology & metabolism, Biology, Receptor, IGF Type 1, Mice, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Endocrinology, Somatomedins, Internal medicine, Testis, medicine, Animals, PTEN, ddc:576.5, Progenitor cell, ddc:612, Spermatogenesis, PI3K/AKT/mTOR pathway, Cell Proliferation, Insulin-like growth factor 1 receptor, Sertoli Cells, urogenital system, PTEN Phosphohydrolase, Sertoli cell, Receptor, Insulin, Cell biology, Insulin receptor, 030104 developmental biology, medicine.anatomical_structure, biology.protein |
| الوصف: | The IGFs are the major intratesticular factors regulating immature Sertoli cell proliferation and are, therefore, critical to establish the magnitude of sperm production. However, the intratesticular source of IGF production and the downstream signaling pathway mediating IGF-dependent Sertoli cell proliferation remain unclear. Single-cell RNA sequencing on mouse embryonic testis revealed a robust expression of Igf1 and Igf2 in interstitial steroidogenic progenitors, suggesting that IGFs exert paracrine actions on immature Sertoli cells. To elucidate the intracellular signaling mechanism that underlies the proliferative effects of IGFs on immature Sertoli cells, we have generated mice with Sertoli cell-specific deletion of the Pten gene, a negative regulator of the phosphatidylinositol-3 kinase (PI3K)/AKT pathway, alone or together with the insulin receptor (Insr) and the IGF1 receptor (Igf1r). Although ablation of Pten appears dispensable for Sertoli cell proliferation and spermatogenesis, inactivation of Pten in the absence of Insr and Igf1r rescued the Sertoli cell proliferation rate during late fetal development, testis size, and sperm production. Overall, these findings suggest that IGFs secreted by interstitial progenitor cells act in a paracrine fashion to promote the proliferation of immature Sertoli cells through the IGF/PTEN/PI3K pathway. |
| تدمد: | 1945-7170 0013-7227 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::181e5955ac81543eb4918680eb2addd1 https://doi.org/10.1210/en.2018-00892 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....181e5955ac81543eb4918680eb2addd1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457170 00137227 |
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