The functions of Sertoli cells in spermatogenesis have attracted much more attention recently. Normal spermatogenesis depends on Sertoli cells, mainly due to their influence on nutrient supply, maintenance of cell junctions, and support for germ cells’ mitosis and meiosis. Accumulating evidence in the past decade has highlighted the dominant functions of the MAPK, AMPK, and TGF-β/Smad signaling pathways during spermatogenesis. Among these pathways, the MAPK signaling pathway regulates dynamics of tight junctions and adherens junctions, proliferation and meiosis of germ cells, proliferation and lactate production of Sertoli cells; the AMPK and the TGF-β/Smad signaling pathways both affect dynamics of tight junctions and adherens junctions, as well as the proliferation of Sertoli cells. The AMPK signaling pathway also regulates lactate supply. These signaling pathways combine to form a complex regulatory network for spermatogenesis. In testicular tumors or infertile patients, the activities of these signaling pathways in Sertoli cells are abnormal. Clarifying the mechanisms of signaling pathways in Sertoli cells on spermatogenesis provides new insights into the physiological functions of Sertoli cells in male reproduction, and also serves as a pre-requisite to identify potential therapeutic targets in abnormal spermatogenesis including testicular tumor and male infertility.

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl⁻and HCO₃⁻transport. Although >95% of all CF male patients are infertile because of congenital bilateral absence of the vas deferens (CBAVD), the question whether CFTR mutations are involved in other forms of male infertility is under intense debates. Here we report that CFTR is detected in both human and mouse sperm. CFTR inhibitor or antibody significantly reduces the sperm capacitation, and the associated HCO₃⁻-dependent events, including increases in intracellular pH, cAMP production and membrane hyperpolarization. The fertilizing capacity of the sperm obtained from heterozygous CFTR mutant mice is also significantly lower compared with that of the wild-type. These results suggest that CFTR in sperm may be involved in the transport of HCO₃⁻important for sperm capacitation and that CFTR mutations with impaired CFTR function may lead to reduced sperm fertilizing capacity and male infertility other than CBAVD.

Endometriosis, an estrogen-dependent chronic gynecological disease, is common in reproductive-age women and profoundly affects their life quality. Although various pathogenic theories have been proposed, the origin of endometriosis remains unclear. Epithelial to mesenchymal transition (EMT) is a process that epithelial cells lose polarized organization of the cytoskeleton and cell-to-cell contacts, acquiring the high motility of mesenchymal cells. These changes are thought to be prerequisites for the original establishment of endometriotic lesions. However, no study exactly indicates which type of EMT occurs in endometriosis. In this review, we conclude that two different types of EMT may participate in this disease. Besides, two stimulating signals, hypoxia and estrogen, can through different pathways to activate the EMT process in endometriosis. Those pathways involve many cellular factors such as TGF-beta and Wnt, ultimately leading to cell proliferation and migration. As infertility is becoming a serious and intractable issue for women, EMT, during the implantation process, is gaining attention. In this review, we will describe the known functions of EMT in endometriosis, and suggest further studies that may aid in the development of medical therapy.

Due to the widespread use of nanomaterials in medical, industrial and military applications, the question as to whether nanoparticles (NPs) cause harmful disturbances in human health, especially on the reproductive system, remains a matter of concern. In this review, we focus mainly on the in vivo and in vitro effects of NPs on spermatogenesis at the clinical, cellular and molecular levels. In general, most NPs display adverse effects on spermatogenesis at these various levels; but, some NPs show no adverse effects. However, the mechanism underlying NP disruption of spermatogenesis and penetration of the blood-testis barrier remains unclear. In this review, we raise many hypotheses for experimental testing in order to elucidate the mechanism.

Factors and pathways involved in capacitation: how are they regulated?