Abnormal Meiosis Initiation in Germ Cell Caused by Aberrant Differentiation of Gonad Somatic Cell
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
Authors: Chen, Min; Chen, Suren; Zhou, Jingjing; Dong, Fangfang; Shen, Zhiming; Wu, Haowei; Cui, Xiuhong; Gao, Fei
Abstract
The interaction between germ cell and somatic cell plays important roles in germ cell development. However, the exact function of gonad somatic cell in germ cell differentiation is unclear. In the present study, the function of gonad somatic cell in germ cell meiosis was examined by using mouse models with aberrant somatic cell differentiation. In Wt1(R394W/R394W) mice, the genital ridge is absent due to the apoptosis of coelomic epithelial cells. Interestingly, in both male and female Wt1(R394W/R394W) germ cells, STRA8 was detected at E12.5 and the scattered SYCP3 foci were observed at E13.5 which was consistent with control females. In Wt1(-/flox); Cre-ERTM mice, Wt1 was inactivated by the injection of tamoxifen at E9.5 and the differentiation of Sertoli and granulosa cells was completely blocked. We found that most germ cells were located outside of genital ridge after Wt1 inactivation. STRA8, SYCP3, and gamma H2AX proteins were detected in germ cells of both male and female Wt1(-/flox); Cre-ERTM gonads, whereas no thread-like SYCP3 signal was observed. Our study demonstrates that aberrant development of gonad somatic cells leads to ectopic expression of meiosis-associated genes in germ cells, but meiosis was arrested before prophase I. These results suggest that the proper differentiation of gonad somatic cells is essential for germ cell meiosis.
Retinoic acid combined with spermatogonial stem cell conditions facilitate the generation of mouse germ-like cells
BIOSCIENCE REPORTS
Authors: Dong, Guoyi; Shang, Zhouchun; Liu, Longqi; Liu, Chuanyu; Ge, Yuping; Wang, Quanlei; Wu, Liang; Chen, Fang; Li, Baolin; Liu, Xin; Xu, Xun; Yang, Huanming; Du, Yutao; Jiang, Hui
Abstract
Spermatogenic lineage has been directly generated in spermatogonial stem cell (SSC) conditions from human pluripotent stem cells (PSCs). However, it remains unknown whether mouse embryonic stem cells (ESCs) can directly differentiate into advanced male germ cell lineage in the same conditions. Here, we showed rather low efficiency of germ-like cell generation from mouse ESCs in SSC conditions. Interestingly, addition of retinoic acid (RA) into SSC conditions enabled efficient differentiation of mouse ESCs into germ-like cells, as shown by the activation of spermatogenesis-associated genes such as Mvh, Dazl, Prdm14, Stella, Scp1, Scp3, Stra8 and Rec8. In contrast, for cells cultured in control medium, the activation of the above genes barely occurred. In addition, RA with SSC conditions yielded colonies of Acrosin-expressing cells and the positive ratio reached a peak at day 6. Our work thus establishes a simple and cost-efficient approach for male germ like cell differentiation from mouse PSCs and may propose a useful strategy for studying spermatogenesis in vitro.