Role of Y Chromosome Microdeletions in the Clinical Evaluation of Infertile Males

Abstract

Infertility is a multifaceted condition, which is on the rise in the last few decades. A stage of great importance in the development of human male gametes is spermatogenesis, which is governed by a set of genes located on the q arm of the Y chromosome. Loss of these genes can cause disruptions in spermatogenesis and, thus, lead to male infertility. Studies have identified several deletions on the long arm of the Y chromosome, called Yq microdeletions, which occur in three distinct loci termed AZFa, AZFb, and AZFc. In addition to these, there exist small subdeletions in the AZFc locus, called gr/gr, b1/b2, or b2/b3 subdeletions. Such deletions can lead to azoospermia or oligozoospermia by causing Sertoli cell-only syndrome, impairment in spermatogenesis, or maturation arrest. Testing for Y chromosome microdeletions is clinically significant for several reasons, since these deletions are exclusively associated with male infertility and their detection can help identify the cause of infertility. Knowing the presence or absence of Y chromosome microdeletion also aids in predicting the prognosis of oligozoospermic males, who are usually known to progress to azoospermia over time. The occurrence and type of Yq microdeletion are correlated with testicular phenotype in infertile males and, thus, serve as a good predictor of sperm retrieval. Vertical transmission of Y chromosome microdeletions from father to the male offspring is common in pregnancies achieved via assisted reproductive technologies; hence, the diagnosis of these deletions becomes imperative in such couples to prevent perpetuation of infertility in the next generation. Screening for Yq microdeletions is, thus, clinically significant and must be offered to all infertile males.