Spermatogenesis最新文献

Primary cell culture is an established and widely used technique to study Sertoli cell function in vitro. However, the relative difficulty of stably overexpressing or knocking down genes in Sertoli cell culture has limited progress in the field. In this technical report, we present a method to transduce 20 dpp rat Sertoli cell cultures with VSV-G pseudotyped lentiviral based vectors at a high rate (~80%), with stable reporter gene expression. Although high transgene expression is desirable, it was noted that at transduction rates > 60% inter-Sertoli cell tight junction integrity and, hence, Sertoli cell function, were transiently compromised. We envisage that this optimized procedure has the potential to stimulate Sertoli cell research, and motivate the use of Sertoli cells in various cell therapy applications.

Male obesity in reproductive-age men has nearly tripled in the past 30 y and coincides with an increase in male infertility worldwide. There is now emerging evidence that male obesity impacts negatively on male reproductive potential not only reducing sperm quality, but in particular altering the physical and molecular structure of germ cells in the testes and ultimately mature sperm. Recent data has shown that male obesity also impairs offspring metabolic and reproductive health suggesting that paternal health cues are transmitted to the next generation with the mediator mostly likely occurring via the sperm. Interestingly the molecular profile of germ cells in the testes and sperm from obese males is altered with changes to epigenetic modifiers. The increasing prevalence of male obesity calls for better public health awareness at the time of conception, with a better understanding of the molecular mechanism involved during spermatogenesis required along with the potential of interventions in reversing these deleterious effects. This review will focus on how male obesity affects fertility and sperm quality with a focus on proposed mechanisms and the potential reversibility of these adverse effects.

The generation of functional sperm in vitro has been a goal for almost a century. Until recently, researchers have only succeeded in reproducing the early steps of spermatogenesis. This is not surprising given that spermatogenesis is a complicated process that requires the coordinated efforts of germ cells and several somatic cells within the tubular structure of the testis. Finally-last year-Sato et al. reported the successful in vitro production of functional sperm, thereby potentially opening up a new era of reproductive biology. Here, we summarize the history of research directed toward reproducing steps of spermatogenesis in vitro, detail the seminal findings of Sato et al., and suggest ways that their approach can be applied toward clinical applications and addressing fundamental questions about the underlying mechanism of spermatogenesis.

CD147, also named basigin (Bsg) or extracellular matrix (ECM) metalloproteinase inducer (EMMPRIN), is a highly glycosylated protein first identified as a tumor cell surface molecule. In cancer, it is well established that CD147 promotes metastasis by stimulating the production of MMPs. Recent studies have also suggested that it may be associated with tumor growth and angiogenesis. Interestingly, CD147 is expressed in germ cells of different development stages in the testis and its knockout mice are infertile, indicating an essential role of CD147 in spermatogenesis. While the detailed involvement of CD147 in spermatogenesis remains elusive, our recent findings have revealed a dual role of CD147 in germ cell development. On the one hand, it regulates the migration of spermatogonia and spermatocytes via the induction of MMP-2 production; on the other hand, it specifically regulates the survival/apoptosis of spermatocytes but not spermatogonia through a p53-independent pathway. In this review, we aim to provide an overview on the functions of CD147, comparing its roles in cancer and the testis, thereby providing new insights into the regulatory mechanisms underlying the process of spermatogenesis.

Vasectomy is the most common urological procedure in the United States with 18% of men having a vasectomy before age 45. A significant proportion of vasectomized men ultimately request vasectomy reversal, usually due to divorce and/or remarriage. Vasectomy reversal is a commonly practiced but technically demanding microsurgical procedure that restores patency of the male excurrent ductal system in 80-99.5% of cases and enables unassisted pregnancy in 40-80% of couples. The discrepancy between the anastomotic patency rates and clinical pregnancy rates following vasectomy reversal suggests that some of the biological consequences of vasectomy may not be entirely reversible in all men. Herein we review what is known about the biological sequelae of vasectomy and vasectomy reversal in humans, and provide a succinct overview of the evaluation and surgical management of men desiring vasectomy reversal.

Many previous studies have aimed at spermatogenesis of male murine germ cells in vitro, but no efficient system has been established yet that covers the entire process of mammalian spermatogenesis in a culture dish permanently. In this review, we report on the requirements of spermatogenesis and the current state of different culture methods using testicular tissue fragments, single cell suspensions or three-dimensional culture environments.

The blood-testis barrier (BTB) provides an efficient barrier to restrict paracellular and transcellular transport of substances, such as toxicants and drugs, limiting their entry to the testis to cause injury. This is achieved by the coordinated actions of efflux and influx transporters at the BTB, which are integral membrane proteins that interact with their substrates, such as drugs and toxicants. An efflux transporter (e.g., P-glycoprotein) can either restrict the entry of drugs/toxicants into the testis or actively pump drugs/toxicants out of Sertoli and/or germ cells if they have entered the seminiferous epithelium via influx pumps. This thus provides an effective mechanism to safeguard spermatogenesis. Using Sertoli cells cultured in vitro with an established tight junction (TJ)-permeability barrier which mimicked the BTB in vivo and treated with cadmium chloride (CdCl2), and also in adult rats (~300 g b.w.) treated with CdCl2 (3 mg/kg b.w., via i.p.) to induce testicular injury, cadmium was found to significantly downregulate the expression of efflux (e.g., P-glycoprotein, Mrp1, Abcg1) and influx (e.g., Oatp3, Slc15a1, Scl39a8) transporters. For instance, treatment of Sertoli cells with cadmium induced significant loss of P-glycoprotein and Oatp-3 at the cell-cell interface, which likely facilitated cadmium entry into the Sertoli cell. These findings illustrate that one of the mechanisms by which cadmium enters the testis is mediated by downregulating the expression of drug transporters at the BTB. Furthermore, cytokines and steroids were found to have differential effects in regulating the expression of drug transporters. Summary, the expression of drug transporters in the testis is regulated by toxicants, steroids and cytokines.