Genetic causes of spermatogenic failure

Abstract

Approximately 10%-15% of couples are infertile, and a male factor is involved in almost half of these cases. This observation is due in part to defects in spermatogenesis, and the underlying causes, including genetic abnormalities, remain largely unknown. Until recently, the only genetic tests used in the diagnosis of male infertility were aimed at detecting the presence of microdeletions of the long arm of the Y chromosome and/or chromosomal abnormalities. Various other single-gene or polygenic defects have been proposed to be involved in male fertility. However, their causative effects often remain unproven. The recent evolution in the development of whole-genome-based techniques and the large-scale analysis of mouse models might help in this process. Through knockout mouse models, at least 388 genes have been shown to be associated with spermatogenesis in mice. However, problems often arise when translating this information from mice to humans.

Y chromosome microdeletions in infertile men: prevalence, phenotypes and screening markers for the Indian population

“…The results revealed an overall frequency of Yq microdeletions to be 5.8 % (215/3,647) in the infertile individuals. This frequency is lower than those reported in meta-analysis (7.4-8.2 %) performed on world literature [13,18]. These observations imply that although the Yq microdeletions contribute towards male infertility in the Indian population, the association appears somewhat less than that observed in the Western counterparts.…”

“…Analysis of large datasets internationally has demonstrated the prevalence of Yq microdeletions in the range of 7-10 % [18,29]. The diagnosis of Yq microdeletions is considered to be clinically relevant for appropriate counseling and management of male infertility and is highly recommended for cases undertaking ICSI as a fertility treatment option owing to 100 % transmission of the genetic defect to the male offspring from fathers carrying the microdeletions.…”

“…Since its first description in a subset of azoospermic men [25], Yq microdeletions have been described in a spectrum of infertile men, the incidence of Yq microdeletions is estimated to be 7-8 % with a wide variation across populations [13,18].…”

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

“…Microdeletions involving the Azoospermia Factor loci (AZF) on the long arm of the Y chromosome (Yq) are a genetic cause of male infertility and the deletions of the AZFa, AZFb or AZFc loci alone or in combination occur in 2-10 % of men with abnormal seminogram [2][3][4][5][6]. Since Yq microdeletions can be vertically transmitted to the male offspring born after assisted reproduction [7,8], screening for these microdeletions has become a part of the routine diagnostic workup for men with azoospermia or oligozoospermia [5].…”

Association of progesterone receptor gene polymorphism with male infertility and clinical outcome of ICSI

“…Microdeletions on the long arm of the Y chromosome (Yq), encompassing critical genes involved in spermatogenesis, has been observed in 5-10 % of infertile men [1,14,26,35]. In addition, mutations/polymorphisms in several autosomal genes have been identified in a subset of individuals with male factor infertility [15,26]. Genome-wide association studies have identified multiple autosomal loci across the genome that may be implicated in male factor infertility [10,18,21].…”