Study on the effect of glucocorticoid on apoptosis of rat spermatogenic cells

The effect of glucocoiticoid on the apoptosis of rat spermato-genic cells labeled with TUNEL was observed in vivo by laser con-focal microscopy and electron microscopy. The results showed thatlarge doses of glucocorticoid increased the apoptosis of rat spermto-genic cell. (Chin J Androl 2001; 2: 98-101)

Corrigendum to"Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells"

There is an error in the second affiliation in the published article by Wang et al.!The correct afiliation for the authors,Xi Zhang and Ming-Han Tong,should be:“2State Key Laboratory of Molecular Biology,Shanghai Key Laboratory of Molecular Andrology,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China”.

Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells(SSCs).However,such therapy for infertility has not been experimentally investigated yet.In this study,a mouse model with an X-linked testis-expressed 11(TEX11)mutation(Tex11PM/Y)identified in azoospermia patients exhibited meiotic arrest due to aberrant chromosome segregation.Tex11PM/Y SSCs could be isolated and expanded in vitro normally,and the mutation was corrected by clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated endonuclease 9(Cas9),leading to the generation of repaired SSC lines.Whole-genome sequencing demonstrated that the mutation rate in repaired SSCs is comparable with that of autonomous mutation in untreated Tex11PM/Y SSCs,and no predicted off-target sites are modified.Repaired SSCs could restore spermatogenesis in infertile males and give rise to fertile offspring at a high efficiency.In summary,our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy.

Mechanistic target of rapamycin kinase(Mtor)is required for spermatogonial proliferation and differentiation in mice

Spermatogonial development is a vital prerequisite for spermatogenesis and male fertility.However,the exact mechanisms underlying the behavior of spermatogonia,including spermatogonial stem cell(SSC)self-renewal and spermatogonial proliferation and differentiation,are not fully understood.Recent studies demonstrated that the mTOR complex 1(mTORC1)signaling pathway plays a crucial role in spermatogonial development,but whether MTOR itself was also involved in any specific process of spermatogonial development remained undetermined.In this study,we specifically deleted Mtor in male germ cells of mice using Stra8-Cre and assessed its effect on the function of spermatogonia.The Mtor knockout(KO)mice exhibited an age-dependent perturbation of testicular development and progressively lost germ cells and fertility with age.These age-related phenotypes were likely caused by a delayed initiation of Mtor deletion driven by Stra8-Cre.Further examination revealed a reduction of differentiating spermatogonia in Mtor KO mice,suggesting that spermatogonial differentiation was inhibited.Spermatogonial proliferation was also impaired in Mtor KO mice,leading to a diminished spermatogonial pool and total germ cell population.Our results show that MTOR plays a pivotal role in male fertility and is required for spermatogonial proliferation and differentiation.

Meiosis: no end in sight

Meiosis is an essential event that generates haploid gametes from diploid progenitors in all sexually reproducing organisms. It involves a single round of DNA replication followed by two rounds of chromosome segregation: separating homologous chromosomes (homologs;meiosis I [MI]), then sister chromatids (meiosis II [MII]). During the first meiotic prophase (MI prophase), homologs undergo recombination, pairing, and synapsis through the formation of the synaptonemal complex (SC). Recombination, the most prominent feature in meiosis, can increase genetic diversity during inheritance and generate physical connections between homologs to ensure their accurate segregation at MI prophase. In humans, meiotic errors can result in either infertility or gametic aneuploidy/mutation (hence, miscarriage or birth defects). With technological advances in the past few decades, researchers have made rapid progress in the field of meiosis. This special issue contains seven papers: five are reviews summarizing our current knowledge on meiosis (in particular mammalian MI prophase), and one is commentary highlighting an original research article on CRISPR-Cas9-based gene therapy for the treatment of meiotic arrest azoospermia in mice.

DNA/RNA helicase DHX36 is required for late stages of spermatogenesis

Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.