دورية أكاديمية
Deleterious variants in X-linked RHOXF1 cause male infertility with oligo- and azoospermia
| العنوان: | Deleterious variants in X-linked RHOXF1 cause male infertility with oligo- and azoospermia |
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| المؤلفون: | Yi, Sibing, Wang, Weili, Su, Lilan, Meng, Lanlan, Li, Yong, Tan, Chen, Liu, Qiang, Zhang, Huan, Fan, Liqing, Lu, Guangxiu, Hu, Liang, Du, Juan, Lin, Ge, Tan, Yue-Qiu, Tu, Chaofeng, Zhang, Qianjun |
| المساهمون: | National Key Research and Developmental Program of China, National Natural Science Foundation of China, Outstanding Youth Foundation of Hunan Provincial Natural Science Foundation of China, Hunan Provincial Natural Science Foundation of China, China Postdoctoral Science Foundation, Graduate Research Innovation Project of Central South University |
| المصدر: | Molecular Human Reproduction ; volume 30, issue 2 ; ISSN 1360-9947 1460-2407 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Cell Biology, Developmental Biology, Obstetrics and Gynecology, Genetics, Molecular Biology, Embryology, Reproductive Medicine |
| الوصف: | Oligozoospermia and azoospermia are two common phenotypes of male infertility characterized by massive sperm defects owing to failure of spermatogenesis. The deleterious impact of candidate variants with male infertility is to be explored. In our study, we identified three hemizygous missense variants (c.388G>A: p.V130M, c.272C>T: p.A91V, and c.467C>T: p.A156V) and one hemizygous nonsense variant (c.478C>T: p.R160X) in the Rhox homeobox family member 1 gene (RHOXF1) in four unrelated cases from a cohort of 1201 infertile Chinese men with oligo- and azoospermia using whole-exome sequencing and Sanger sequencing. RHOXF1 was absent in the testicular biopsy of one patient (c.388G>A: p.V130M) whose histological analysis showed a phenotype of Sertoli cell-only syndrome. In vitro experiments indicated that RHOXF1 mutations significantly reduced the content of RHOXF1 protein in HEK293T cells. Specifically, the p.V130M, p.A156V, and p.R160X mutants of RHOXF1 also led to increased RHOXF1 accumulation in cytoplasmic particles. Luciferase assays revealed that p.V130M and p.R160X mutants may disrupt downstream spermatogenesis by perturbing the regulation of doublesex and mab-3 related transcription factor 1 (DMRT1) promoter activity. Furthermore, ICSI treatment could be beneficial in the context of oligozoospermia caused by RHOXF1 mutations. In conclusion, our findings collectively identified mutated RHOXF1 to be a disease-causing X-linked gene in human oligo- and azoospermia. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/molehr/gaae002 |
| DOI: | 10.1093/molehr/gaae002/56334812/gaae002.pdf |
| الإتاحة: | https://doi.org/10.1093/molehr/gaae002Test https://academic.oup.com/molehr/article-pdf/30/2/gaae002/56641681/gaae002.pdfTest |
| حقوق: | https://academic.oup.com/pages/standard-publication-reuse-rightsTest |
| رقم الانضمام: | edsbas.70A43F4C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/molehr/gaae002 |
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