The Role of Number of Copies, Structure, Behavior and Copy Number Variations (CNV) of the Y Chromosome in Male Infertility

Abstract

The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30-40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome.

An NGS‐based approach to identify Y‐chromosome variation in non‐obstructive azoospermia

“…Y‐chromosome microdeletions, especially AZFa‐c deletions, have been identified as pathogenic CNVs in spermatogenesis (Signore et al., 2019); however, Y chromosome‐linked duplications and complex CNVs have rarely been studied due to the technical limitations. Herein, we discuss Y chromosome‐linked CNVs in a Chinese population using the NGS method.…”

Eef2k is not required for fertility in male mice

“…Infertility is estimated to impact 8-12% of couples worldwide, and is defined by a failure to conceive following unprotected frequent sexual intercourse over a one-year period. Approximately half of infertile couples are impacted by male-factor infertility (1), which can occur due to hormonal deficits (2), physical causes, sexually transmitted diseases, or environmental, lifestyle (3,4), and genetic factors (5,6). As spermatogenesis is a key process in the maintenance of appropriate male fertility, any abnormalities in the generation of spermatozoa can give rise to male-factor infertility (7).…”

The Association Study between Tumor Necrosis Factor- Receptor 1 36 A/G (TNFR1 36 A/G) Gene Polymorphism and Azoospermic Infertile Men in Erbil City

“…Chromosomal diseases are mostly founded in infertile compared with fertile population (Signore et al 2020). These chromosomal changes found in 20% of azoospermic and the Klinefelter syndrome (47,XXY) is most frequent genetic causes of azoospermia (or severe oligozoospermia) ( Röpke.…”