MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation.

Male fertility rates have shown a progressive decrease in both developing and industrialised countries in the past 50 years. Clinical and epidemiological studies have demonstrated controversial results about the harmful effects of cigarette smoking on seminal parameters. Some studies could not establish a negative effect by tobacco smoking on sperm quality and function, whereas others have found a significant reduction in sperm quality and function. This study reviews the components in cigarette smoke and discusses the effects of smoking on male fertility by focusing extensively on smoking-induced genetic and epigenetic alterations in infertile men. Chromosomal aneuploidies, sperm DNA fragmentation and gene mutations are discussed in the first section, while changes in DNA methylation, chromatin remodelling and noncoding RNAs are discussed in the second section as part of epigenetic alterations.

Infertility is defined as a condition where a couple does not achieve a pregnancy after one year of regular, unprotected sexual intercourse and affects 8%-12% of couples worldwide (Inhorn & Patrizio, 2015; Sharlip et al., 2002). A male factor is the cause of infertility in approximately 50% of the couples. All the reasons of male factor infertility are not known exactly, and in spite of the progress in the field of male reproductive health, 30%-40% of the infertility cases have still no detectable cause and remain as idiopathic (Agarwal et al., 2019; Bracke et al., 2018). Idiopathic forms of male infertility may result from unknown genetic and/or epigenetic factors (Gunes & Esteves, 2020; Neto et al., 2016). Spermatogenesis with a unique epigenetic pattern (Gannon et al., 2014) is exposed to several intrinsic and/or extrinsic factors, culminating in DNA damage in various types of germ cells (Singh et al., 2019b). In germ cells, DNA damage may also result from abnormalities in the protamination process (Muratori & De

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Androgens, testosterone and dihydrotestosterone (DHT) are endocrine regulators of spermatogenesis and act via androgen receptor (AR). The aim of this study was to investigate the association(s) of AR (CAG repeat length), SRD5A2 (rs523349, V89L) and TNFα (rs1800629, -308G/A) polymorphisms with idiopathic male infertility in Turkish men. This case-control study consisted of 312 men with idiopathic infertility and 113 fertile men. Polyacrylamide gel electrophoresis (PAGE) or PCR-restriction fragment length polymorphism methods were used for genotyping. The mean AR CAG repeat length was significantly longer in infertile men than in fertile men (p = 0.015).However, there was no significant association between the SRD5A2 genotypes (VV, VL and LL) and the risk of infertility (p = 0.516). The genotype frequency and allele distribution of TNFα -308G/A polymorphism (GG, GA, AA genotypes and G, A alleles) were not associated with male infertility (p = 0.779 and p = 0.743 respectively).AR CAG repeat expansion might be one of the risk factors for idiopathic male infertility in Turkish men. Further studies investigating the association of male infertility with AR CAG, V89L and -308G/A polymorphisms are warranted to understand the possible associations among them.

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Sex determination is a complex and dynamic process with multiple genetic and environmental causes, in which germ and somatic cells receive various sex‐specific features. During the fifth week of fetal life, the bipotential embryonic gonad starts to develop in humans. In the bipotential gonadal tissue, certain cell groups start to differentiate to form the ovaries or testes. Despite considerable efforts and advances in identifying the mechanisms playing a role in sex determination and differentiation, the underlying mechanisms of the exact functions of many genes, gene–gene interactions, and epigenetic modifications that are involved in different stages of this cascade are not completely understood. This review aims at discussing current data on the genetic effects via genes and epigenetic mechanisms that affect the regulation of sex determination. Birth Defects Research (Part C) 108:321–336, 2016. © 2016 Wiley Periodicals, Inc.