According to the official statistics of the World Health Organization, at least 48 million couples and 186 million people suffer from infertility. Varicocele has been recognized as the leading cause of male infertility and can affect spermatogenesis and cause testicular and epididymal disorders through multiple diverse pathophysiological processes. Reactive oxygen species (ROS) produced by oxidative stress have been reconciled as an important pathogenic factor throughout the course of varicocele. Testis respond to heat stress, hypoxia, and inflammation at the cost of producing excessive ROS. High levels of ROS can lead to infertility not only through lipid peroxidation or DNA damage, but also by inactivating enzymes and proteins in spermatogenesis. This review studies the oxidative stress and its role in the pathophysiology and molecular biology of varicocele in the context of a decline in fertility.

Long non-coding RNAs (lncRNAs) have been found to participate in the regulation of human spermatogenic cell development. However, little is known about the abnormal expression of lncRNAs associated with spermatogenic failure and their molecular mechanisms. Using lncRNA microarray of testicular tissue for male infertility and bioinformatics methods, we identified the relatively conserved lncRNA Gm2044 which may play important roles in non-obstructive azoospermia. The UCSC Genome Browser showed that lncRNA Gm2044 is the miR-202 host gene. This study revealed that lncRNA Gm2044 and miR-202 were significantly increased in non-obstructive azoospermia of spermatogonial arrest. The mRNA and protein levels of Rbfox2, a known direct target gene of miR-202, were regulated by lncRNA Gm2044. Furthermore, the miR-202-Rbfox2 signalling pathway was shown to mediate the suppressive effects of lncRNA Gm2044 on the proliferation of human testicular embryonic carcinoma cells. Understanding of the molecular signalling pathways for lncRNA-regulated spermatogenesis will provide new clues into the pathogenesis and treatment of patients with male infertility.

To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), reduced folate carrier1 (RFC-1), methionine synthase (MTR) involved in folate metabolism and the risk of offsprings of young Chinese women with Down syndrome (DS) through a case-control study, the polymorphisms of MTHFR 677C>T, MTRR 66A>G, RFC-1 80G>A, and MTR 2756A>G in 60 mothers of children with DS and 68 control mothers were investigated by PCR-RFLP. Significant differences in alle-lic frequencies were present between the cases and controls for MTHFR (Plt;0.05), but not in allelic frequencies for MTRR, RFC-1, and MTR. Homozygous MTHFR 677C>T polymorphism was more prevalent among the mothers of children with DS than among the control mothers, with an odds ratio of 3.51 (OR=3.51, 95% CI=1.30~9.46, Plt;0.05). No significant association was observed in the combined heterozygotes. In addition, the homozygous MTRR 66A>G polymorphism was independently associated with a 3.16-fold increase in estimated risk (OR=3.16, 95% CI=1.20~8.35, Plt;0.05). The increased risk of DS for homozygous RFC-1 80G>A was not associated with MTR 2756A>G. Positive interactions were found for the following genotype-pairs: MTHFR(CT+TT)/MTRR GG, MTHFR (CT+TT)/RFC-1 AA, MTHFR CC/MTR(AG+GG), MTHFR (CT+TT)/MTR AA, MTRR GG/MTR AA, and RFC-1 AA/MTRAA. In conclusion, MTHFR 677C>T and MTRR 66A>G polymorphisms are two independent risk factors for DS pregnancies in young women, but RFC-1 80G>A and MTR 2756A>G polymorphism are not independent risk factor. A role for combined genotypes in the risk of DS pregnancies cannot be excluded.

Complex chromosome rearrangements (CCRs) are constitutional structural rearrangements involve more than two breakpoints on two or more chromosomes. Balanced CCR carriers are often phenotypically normal but associated with high risk of spontaneous abortion and having abnormal offspring with unbalanced karyotype. Here, we report a new familial case of complex chromosome structural aberrations involving chromosomes 3, 18 and 21 and four breakpoints.

Varicoceles (VCs) have received widespread attention as a primary factor affecting male fertility and a pathological condition that may lead to decreased sperm count and motility in patients. Many studies have shown that an imbalance of local antioxidant balance exists in patients with VC, leading to an obvious increase in the content of reactive oxygen species (ROS) and may cause reductive stress. Excessive ROS may aggravate spermatogenesis dysfunction and affect male fertility. Poly(ADP-ribose) polymerase (PARP) is an enzyme associated with DNA repair in eukaryotic cells, can be activated by DNA fragments with structural damage, and has been considered a DNA damage receptor in DNA damage repair and apoptosis. We built a rat model of VC and an oxidative damage model of a spermatocyte-derived cell line (GC-2 cells) induced by hydrogen peroxide to study the role of PARP1 in VC. Differentially expressed genes (DEGs) were obtained by RNA sequencing in the testes of VC rats. Analysis of DEGs revealed some genes with significantly altered expression, which were validated in rat and cell models. Immunofluorescence, real-time quantitative PCR analysis, Western blot, and flow cytometry were used to analyze the changes between the control group and the VC or hydrogen peroxide group. Overall, we found that PARP1 protein expression increased in VC rats and in the hydrogen peroxide-induced oxidative stress model of GC-2 cells. Parthanatos may be one of the factors leading to reduced reproductive capacity in VC patients. Our study provides novel insights into the mechanisms of male infertility induced by oxidative stress and provides a new therapeutic target for VC.