Role of genetics and epigenetics in male infertility

Abstract

Male infertility is a heterogeneous and common condition that might be a result of genetic or epigenetic variations or both. The frequency of genetic aberrations in azoospermic or severely oligozoospermic men is at least 15%, and the major genetic causes are karyotype abnormalities, microdeletions on Y chromosome, and mutations of cystic fibrosis transmembrane conductance regulator (CFTR) (Hamada, Esteves, & Agarwal, 2013; Hotaling & Carrell, 2014). Beyond these widely accepted genetic causes, a number of both autosomal and particularly X-chromosomal genes are associated with male infertility (Ropke & Tuttelmann, 2017). Furthermore, epigenetic control of gene expression plays a crucial role in both sperm function and fertilising ability (Gunes, Arslan, Hekim, & Asci, 2016a). Epigenetic regulation might be changed by external and internal factors or both, including environmental factors, nutrition and stress (Gunes, 2018b). This review summarises the latest evidence concerning the role of genetics and epigenetics on male infertility. 1.1 | Overview of human genome and genetics The haploid human genome consists of about 3 billion letters (3.3 billion nucleotides) distributed in 24 chromosomes. However, only 1.5% of the human genome encodes a protein (Gregory & Gilbert, 2005; Maher, 2012). The human genome project (HGP) has shown that genomes of nonrelated people exhibit a single base variation in every 1,200-1,500 DNA bases. These variations are

Multiscale analysis of SRY‐positive 46,XX testicular disorder of sex development: Presentation of nine cases

“…Hence, SRY‐negative patients tend to be more frequently having genital ambiguities compared to SRY‐positive ones. Approximately 80%–90% of 46,XX TDSD patients have SRY gene which is usually translocated on the distal portion of the short arm of an X chromosome (Chen et al., 2019; Dauwerse, Hansson, Brouwers, Peters, & Breuning, 2006; Gunes & Esteves, 2020; Queralt et al., 2008; Ropke & Tuttelmann, 2017; Zenteno‐Ruiz et al., 2001). Typical features of SRY‐positive 46,XX TDSD patients are female karyotype with completely normal male phenotype and virilised male external genitalia, small testes, azoospermia and hypergonadotropic hypogonadism (Akinsal, Baydilli, Demirtas, Saatci, & Ekmekcioglu, 2017; Ropke & Tuttelmann, 2017).…”

Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations

“…Aktan et al, 2013;Gill et al, 2019;Homa et al, 2019;Le et al, 2019;Simon et al, 2013). Men with idiopathic infertility have abnormal semen parameters-on a routine semen analysis-but no identifiable male factor(Agarwal et al, 2019;Darbandi et al, 2019;Gunes & Esteves, 2020).…”

SPATS1 (spermatogenesis-associated, serine-rich 1) is not essential for spermatogenesis and fertility in mouse

“…The alteration of spermatogenic gene expression programs is at the basis of numerous pathologies, including infertility [6][7][8][9][10][11] and testicular cancer [12]. However, owing to some intrinsic obstacles-namely the high cell heterogeneity of testicular tissue, and the lack of reliable in vitro cultures [13][14][15][16]-the studies on the molecular groundwork of spermatogenesis, including the identification of those genes that are essential for fertility, have been hampered.…”