| Spermatogenesis, which happened in seminiferous tubule, is a complex process of growth and maturation. There are many different factors which can lead to the failure of the male germ cell development. Along with the increasingly serious stress and environmental pollution situation, the incidence of infertility between normal couples of child-bearing age is constantly increase. Among them, the cases caused by male factors accounted for about50%, and most of unknown etiology. Infertility has become a major clinical, social and economic problems. Previous studies showed that due to genetic factors caused abnormal sperm production obstacle at least accounted for more than half of male infertility.Therefore, elucidating the underlying molecular mechanism of male infertility may help to improve the clinical diagnosis and treatment of male infertility.Sertoli cell is located at the base of seminiferous tubule, and provide support of spermatogenesis. Blood-testis barrier (BTB) is constituted by adjacent Sertoli cells. BTB is a natural immune barrier in testis, and can provide a stable environment for normal spermatogenesis. During VIII-XI stages of seminiferous epithelium cycle, the preleptotene/leptotene spermatocytes transit the BTB for further development. The destruction of the BTB may lead to the damage of testicular immune barrier, resulting in male infertility.It has been recently ascribed to several inflammatory cytokines (i.e. TGF-β3, TNF-α, and IL-1) a functional role in regulating Sertoli cell blood-testis barrier (BTB) dynamics. In the testis, IL-6inhibits meiotic DNA synthesis during the seminiferous epithelium cycle, reduces sperm motility and influences the secretion of transferrin and inhibin B by Sertoli cells. Also, it has been shown that IL-6affects tight junction permeability in Sertoli cells, but, little is known about its role in regulating the BTB. The aim of this study was to investigate the molecular mechanisms by which IL-6affects BTB dynamics. We show that IL-6perturbs the integrity of the BTB, and alters the normal localization and steady-state levels of BTB integral membrane proteins. We demonstrated that IL-6regulates the BTB by inhibiting the degradation of BTB constitutive proteins and activating ERK-MAPK pathways. Our results provide mechanistic insight into the roles of IL-6in regulating BTB dynamics.The chromatoid body (CB) is a specific finely filamentous structure in the cytoplasm of haploid spermatids. In mammalian, CB appears for the first time in the cytoplasm of spermatocytes as a granular structure in the interstices of mitochondria clusters. Then CB condenses into a cloud-like perinuclear granule in round spermatids. In elongate spermatids, CB disappears gradually. Because it contains large amounts of protein, mRNAs and non-coding RNA, CB is identified as a male germ cell specific RNA storage and processing center. Although CB has found for several decades, its function on spermatogenesis and male infertility has remained elusive. Because knockout several constituent of CB caused the male mice sterility, CB is speculated play important roles in spermatogenesis and male infertility.In somatic cells, KH-type splicing regulatory protein (KSRP) is involved in regulating gene expression and maturation of select miRNAs. However, the function of KSRP in spermatogenesis and male infertility remains unclear. In this study, we found that KSRP localizes in CB, and is a new component of CB. KSRP interacts with PABP1, PABP2and RNAs in CB, which indicates that KSRP may be involved in the translation of mRNAs and the maturation of miRNAs in haploid germ cells. Moreover, KSRP may regulate the integrity of CB via Ddx5-miRNA-182using damaged CB models. In addition, we found abnormal expressions of CB components in testis of KSRP knockout mice and of patients with hypospermatogenesis. Thus, our results provide mechanistic insight into the role of KSRP in CB and spermatogenesis. |
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