Genetic Dissection of the AZF Regions of the Human Y Chromosome: Thriller or Filler for Male (In)fertility?

Abstract

The azoospermia factor (AZF) regions consist of three genetic domains in the long arm of the human Y chromosome referred to as AZFa, AZFb and AZFc. These are of importance for male fertility since they are home to genes required for spermatogenesis. In this paper a comprehensive analysis of AZF structure and gene content will be undertaken. Particular care will be given to the molecular mechanisms underlying the spermatogenic impairment phenotypes associated to AZF deletions. Analysis of the 14 different AZF genes or gene families argues for the existence of functional asymmetries between the determinants; while some are prominent players in spermatogenesis, others seem to modulate more subtly the program. In this regard, evidence supporting the notion that DDX3Y, KDM5D, RBMY1A1, DAZ, and CDY represent key AZF spermatogenic determinants will be discussed.

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

“…In addition to Y chromosome microdeletions and other less frequent mutations [6,12,14], several studies have proposed that there may be other factors, possibly associated with the environment and/or specific genetic background, that may affect the susceptibility to suffer spermatogenic defects [1,14,32,33,39,44,45].…”

Progress in understanding the molecular functions of DDX3Y (DBY) in male germ cell development and maintenance

“…Human DDX3 paralogs are housed on the X chromosome (DDX3X) as well as in the nonrecombining region Yq11 of the Y-chromosome (DDX3Y or DBY cleavage of ubiquitin molecules from ubiquitinated proteins (3,9). However, it was shown that USP9Y did not provide essential functions during spermatogenesis; mutations in USP9Y including deletion mutations were found to be transmittable in fertile patients (12)(13)(14).…”

“…The specific infertility phenotypes are associated with deletions in each locus (3,9). The AZFa deletions cause a complete absence of germ cells in the testis seminiferous tubules with preservation of somatic Sertoli cells (the so-called Sertoli Cell-Only Syndrome; SCOS) (10,11).…”

Management of non‐obstructive azoospermia

“…Deletions affecting the AZF region have been reported in 8-12 % of NOA patients [63]. The most frequently deleted region is AZFc (80 %), followed by deletion of AZFb (1-5 %), AZFa (0.5-4 %), and AZFb?c (1-3 %) [83][84][85]. Evaluation of microdeletion in the AZF region is clinically important because it can predict SRR during micro-TESE.…”