The role of number of copies, structure, behavior and copy number variations (CNV) of the Y chromosome in male infertility

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 thetwo 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, nohistory of familial fertility-related diseases and a normal panel of values as for endocrine, genetic andbiochemical markers. Idiopathic male infertility may be the result of gene/environment interactions,genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosomerepresent a minor yet significant proportion and are the topic discussed in this review. We searchedthe PubMed database and major search engines for reports about Y-linked male infertility. We presentcases 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 numbervariations (CNVs). We discuss possible explanations of male infertility caused by mutations, loweror higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosomestructural anomalies are not a major cause of male infertility, in case of negative results and of normalDNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, werecommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, withan emphasis on the structure and number of this chromosome.