The epididymal immune balance:a key to preserving male fertility

Up to 15%of male in fertility has an immuno logical origi n,either due to repetitive infections or to autoimmune resp on ses mainly affecting the epididymis,prostate,and testis.Clinical observations and epidemiological data clearly contradict the idea that the testis confers immune protection to the whole male genital tract.As a consequenee,the epididymis,in which posttesticular spermatozoa mature and are stored,has raised some in terest in recent years when it comes to its immune mecha nisms.In deed,sperm cells are produced at puberty,long after the establishment of self-toleranee,and they possess unique surface proteins that cannot be recognized as self.These are potential targets of the immune system,with the risk of inducing autoantibodies and consequently male infertility.Epididymal immunity is based on a finely tuned equilibrium between efficient immune responses to pathogens and strong tolerance to sperm cells.These processes rely on incompletely described molecules and cell types.This review compiles recent studies focusing on the immune cell types populating the epididymis,and proposes hypothetical models of the organization of epididymal immunity with a special emphasis on the immune response,while also discussing important aspects of the epididymal immune regulation such as tolerance and tumour control.

Serum vitamin D content is associated with semen|parameters and serum testosterone levels in men

The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels.This is a crosssectional study conducted at Androscience,Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo,Brazil,with 508 male patients,aged 18-60 years,from 2007 to 2017.Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria.Patients were divided into normozoospermic group(NZG,n=124)and a group with seminal abnormalities(SAG,n=136).Evaluation included complete physical examination,past medical history,habits and lifestyle factors,two complete seminal analysis with sperm functional tests,serum levels of 25-hydroxy-vitamin D_(3)(25(OH)VD_(3)),total and free testosterone,luteinizing hormone(LH),follicle-stimulating hormone(FSH),sex hormone-binding globulin(SHBG),total cholesterol,homeostatic model assessment of insulin resistance(HOMA-IR)index,and karyotype.The mean concentration of 25(OH)VD_(3)was significantly lower in the SAG(P<0.001)and positively correlated with all baseline seminal parameters and total testosterone levels.In addition,serum vitamin D_(3)concentration was found to be positively correlated with sperm concentration(β=2.103;P<0.001),total number of spermatozoa with progressive motility(β=2.069;P=0.003),total number of motile spermatozoa(β=2.571;P=0.015),and strict morphology(β=0.056;P=0.006),regardless of other variables.This is the first comparative study to address the issue of serum vitamin D_(3)content between normozoospermic patients and those with sperm abnormalities.It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality,male reproductive potential,and testosterone levels.

Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice

The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic acids.In mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal segment.Accordingly,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 mice.To explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m mice.This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-mice.In agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and PIWIL2.The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-mice.Importantly,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.

睾丸后精子成熟，不育与高胆固醇血症

胆固醇是参与哺乳动物生理活动的重要分子，由于它是固醇类激素合成的通用前体物质，因而对生殖系统尤为重要。胆固醇不仅仅对于配子发生起到重要作用，它也是公认的精子功能的调节分子。胆固醇体内平衡的调节对睾丸后精子的成熟至关重要，胆固醇水平失衡会影响到睾丸后调控事件。代谢性脂质紊乱（血脂异常症）会影响男性的生育能力，但大多数这方面的研究是从内分泌/睾丸的角度进行探讨的，而这篇综述将关注像高胆固醇血症这样的特定血脂异常症在哺乳动物精子的睾丸后成熟过程中的有害影响。