Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
National Research Institute for Family Planning, WHO Collaboration Center of Human Reproduction, Da Hui Si Road, Beijing 100081, China.
Cell Death Dis. 2017 May 18;8(5):e2795. doi: 10.1038/cddis.2017.110.
Spermatogenesis, the process by which haploid sperm cells are produced from a diploid precursor cell, is essential for sexual reproduction. Here, we report that RING-finger protein 138 (Rnf138) is highly expressed in testes, especially in spermatogonia and spermatocytes. The role of Rnf138 in spermatogenesis was examined using a Rnf138-knockout mouse model. Rnf138 deficiency resulted in increased apoptosis in spermatogenic cells, loss of proliferative spermatogonia, delayed development of spermatozoa and impaired fertility. The proportion of PLZF+Ki67+ cells within the PLZF+ population decreased in the knockout mice. The phenotype was further assessed by RNA-sequencing (RNA-seq), which determined that the expression levels of many genes involved in spermatogenesis were altered in the testis of Rnf138-knockout mice. Thus, Rnf138 deficiency promotes the apoptosis of spermatogenic cells, which may have been caused by the aberrant proliferation of spermatogonia in mouse testis development.
精子发生是指由二倍体前体细胞产生单倍体精子细胞的过程，对于有性繁殖至关重要。在这里，我们报告 RING 指蛋白 138（Rnf138）在睾丸中高度表达，特别是在精原细胞和精母细胞中。使用 Rnf138 敲除小鼠模型研究了 Rnf138 在精子发生中的作用。Rnf138 缺乏导致生殖细胞凋亡增加、增殖性精原细胞丢失、精子发育延迟和生育能力受损。PLZF+Ki67+细胞在 PLZF+群体中的比例在敲除小鼠中降低。通过 RNA 测序（RNA-seq）进一步评估了表型，确定 Rnf138 敲除小鼠睾丸中许多参与精子发生的基因的表达水平发生了改变。因此，Rnf138 缺乏促进生殖细胞凋亡，这可能是由于小鼠睾丸发育过程中精原细胞异常增殖所致。
