Current Status of Y Chromosome Microdeletions: Prevalence, Distribution, Implication and Association with Male Infertility in Indian Men- A Review

Abstract

Introduction: Infertility affects about 15% of couples attempting pregnancy and in approximately 50% of these cases, male factors are responsible. Male infertility is clinically characterised by azoospermia and oligozoospermia depending on the amount of loss of genetic material and the size of the affected region on the Y Chromosome Microdeletions (YCM). The majority of genes located in the Y chromosome are involved in male related functions such as spermatogenesis in human, in addition to other endocrine and physiological factors. These microdeletions are located on q arm of Y chromosome, specifically Azoospermia Factor (AZF) region, hence called Yq microdeletions. These deletions are in form of complete/ incomplete, recombination; mutations and Copy Number Variations (CNV) and vary in frequency depending on region, ethnicity, lifestyles and other epigenetic factors. Hence, this study is well reviewed in Indian men with infertility caused by AZF a,b,c and other partial deletions. So, it is important to the one who is affected by these mutations and infertile couples who adopt Assisted Reproductive Technologies (ARTs) after counseling. It is further useful for prediction of testicular sperm retrieval chances. Aim: To review the current status of Yq microdeletion frequency in infertile Indian men with the available data and their correlation with testicular phenotypes as well as other factors. These would also reckon as a supportive to other clinical findings for diagnosis of specific deletion of infertility to adopt ARTs to the infertile couple. Materials and Methods: Various studies including our data were collected to European Molecular Genetics Quality Network (EMQN) as well as analyse these Yq microdeletions screened using specific Sequence Tagged Sites (STS) of available kit like European Academy of Andrology (EAA) and non-EAAs using Polymerase Chain Reaction (PCR) technology. Various researchers from various zones of India contributed to microdeletion screening of Y chromosome using various STS to AZF locus. These data from 30 study groups were compared to geographical areas/zones, Indian populations, environment, selection criteria and other factors in this review. Results: The data on thousands of Y chromosome analysis confirmed that the frequency of microdeletions are affected by sample size, selection criteria of subjects, different geographical regions, ethnicity, Oxidative Stress (OS), Deoxyribonucleic Acid (DNA) fragmentation and food styles in addition to genetic defects. In Indian subcontinent, these deletions contribute to 8.33% from screening of 5435 Y chromosomes (453/5435). Lower percent (5.37%) of Yq microdeletions in Western India than other parts was observed, being highest in South East (20.52%) and North East zones (17.77%) as mentioned in the present study. These variations in Yq microdeletions are attributed to geographic region, foodstyle, other environmental factors and others. AZFc deletions were more prevalent and correlated to azoospermia (referred/ selected, 66%; deleted 61%) from 30/15 citations respectively in present cohort over oligospermic and/or severe oligospermic men followed by b and a sub-regions including b+c, a+b and others in AZF locus. Amongst 30 study groups, 27 exhibited AZFc deletions at higher rate. Conclusion: From these data in India, it was hence noticed that screening of Yq microdeletion is an important criterion and its correlation with spermeograms is very necessary to infer degree of infertility in men. Such cases are strongly suggested to undergo genetic counselling before adoption of ARTS as deletions increase risk of genetic anomalies, low birth weight and congenital malformations in New Births (NB) of Intracytoplasmic Sperm Injection and Testicular Sperm Ejaculates (ICSI/TESE) adopted cases. Thus, Y deletion evaluation reckons the diagnosis of type of male infertility and its prevention in the next generation propagation through ARTs adopting infertile couples after counselling.