The alteration of RhoA geranylgeranylation and Ras farnesylation breaks the integrity of the blood–testis barrier and results in hypospermatogenesis
| العنوان: | The alteration of RhoA geranylgeranylation and Ras farnesylation breaks the integrity of the blood–testis barrier and results in hypospermatogenesis |
|---|---|
| المؤلفون: | Yue Hua, Tianxiang Feng, Chao-Jun Li, Chen Jiang, Bing Yao, Kang Li, Yong-Juan Sang, Haixiang Sun, Jiangnan Wang, Ruilou Zhu, Xiuxing Wang, Xuechun Hu |
| المصدر: | Cell Death and Disease, Vol 10, Iss 6, Pp 1-12 (2019) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, endocrine system, RHOA, Berberine, Immunology, Protein Prenylation, Mice, Transgenic, Spermatocyte, Biology, Article, Tight Junctions, Andrology, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Geranylgeranylation, Multienzyme Complexes, Spermatocytes, Testis, medicine, Animals, Farnesyltranstransferase, Humans, lcsh:QH573-671, Spermatogenesis, Blood-Testis Barrier, Cells, Cultured, Azoospermia, Blood–testis barrier, Mice, Knockout, Sertoli Cells, Spermatid, Disease model, lcsh:Cytology, Cell Biology, Sertoli cell, Germ Cells, 030104 developmental biology, medicine.anatomical_structure, Infertility, 030220 oncology & carcinogenesis, ras Proteins, biology.protein, Protein prenylation, rhoA GTP-Binding Protein |
| الوصف: | Non-obstructive azoospermia (NOA) severely affects male infertility, however, the deep mechanisms of this disease are rarely interpreted. In this study, we find that undifferentiated spermatogonial stem cells (SSCs) still exist in the basal compartment of the seminiferous tubules and the blood–testis barrier (BTB) formed by the interaction of neighbor Sertoli cells (SCs) is incomplete in NOA patients with spermatogenic maturation arrest. The adhesions between SCs and germ cells (GCs) are also broken in NOA patients. Meanwhile, the expression level of geranylgeranyl diphosphate synthase (Ggpps), a key enzyme in mevalonate metabolic pathway, is lower in NOA patients than that in obstructive azoospermia (OA) patients. After Ggpps deletion specifically in SCs, the mice are infertile and the phenotype of the SC-Ggpps−/− mice is similar to the NOA patients, where the BTB and the SC–GC adhesions are severely destroyed. Although SSCs are still found in the basal compartment of the seminiferous tubules, fewer mature spermatocyte and spermatid are found in SC-Ggpps−/− mice. Further examination suggests that the defect is mediated by the aberrant protein isoprenylation of RhoA and Ras family after Ggpps deletion. The exciting finding is that when the knockout mice are injected with berberine, the abnormal cell adhesions are ameliorated and spermatogenesis is partially restored. Our data suggest that the reconstruction of disrupted BTB is an effective treatment strategy for NOA patients with spermatogenic maturation arrest and hypospermatogenesis. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::755fcb0812b0c8d9827090f4c8007dbeTest http://link.springer.com/article/10.1038/s41419-019-1688-9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....755fcb0812b0c8d9827090f4c8007dbe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
|---|