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

F. Signore, C. Gulìa, R. Votino, V.D. Leo, S. Zaami, L. Putignani, S. Gigli, E. Santini, L. Bertacca, A. Porrello, R. Piergentili

Research output: Contribution to journalArticlepeer-review


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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Issue number1
Publication statusPublished - 2020


  • Aneuploidy
  • Copy number variations (CNV)
  • Epigenetics
  • Karyotype
  • Mosaicism
  • androgen receptor
  • short stature homeobox protein
  • testis determining factor
  • aneuploidy
  • centromere
  • chromosome structure
  • copy number variation
  • disease classification
  • DNA fragmentation
  • epigenetics
  • gene mapping
  • gene mutation
  • gene rearrangement
  • gene sequence
  • genetic association
  • genetic regulation
  • genetic variability
  • genotype environment interaction
  • human
  • immunocytochemistry
  • karyotype
  • karyotyping
  • male infertility
  • phenotype
  • point mutation
  • protein cleavage
  • protein degradation
  • protein localization
  • Review
  • sequence homology
  • SHOX gene
  • sperm quality
  • spermatogenesis
  • spermatozoon count
  • spermatozoon motility
  • systematic review
  • time to pregnancy
  • Y chromosome
  • chromosome aberration
  • DNA sequence
  • genetics
  • male
  • mutation
  • Chromosome Aberrations
  • Chromosomes, Human, Y
  • DNA Copy Number Variations
  • Humans
  • Infertility, Male
  • Karyotyping
  • Male
  • Mutation
  • Sequence Analysis, DNA


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