Cytogenetic and Molecular Analysis of Male Infertility: Y Chromosome Deletion During Nonobstructive Azoospermia and Severe Oligozoospermia

Abstract

Reduced male fertility and subfertility can be caused by genetic factors that affect both germ cell development, differentiation, and function; in particular, chromosome abnormalities and Yq microdeletions are a possible cause of spermatogenetic impairment in males as shown by their higher frequency in infertile men than in the general male population. Microdeletion of the long arm of the Y chromosome (Yq) are associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb, and AZFc) that are critical for germ cell development. With the advent of assisted reproductive technology and intracytoplasmic sperm injection, knowledge about the various factors leading to spermatogenic impairment is one of the most important aspects of scientific research. Therefore, this study was designed to identify the frequency of cytogenetic and submicroscopic interstitial deletions in azoospermia factor loci in infertile Indian males. One hundred and eighty males with nonobstructive oligozoospermia and azoospermia were included in this study. Semen analysis was done in each case to determine the spermatogenic status. Individuals were subjected to detailed clinical examination, family history, and endocrinological and cytogenetic study after consent from the patient. Peripheral blood cultures were set up according to standard protocols and 30 G-banded metaphases were analyzed in each case. Numerical and structural chromosomal abnormalities were detected in 40 infertile cases. Fluorescence in situ hybridization analysis was done in some cases to identify the percentage of mosaic cell lines and any cryptic or low-level mosaicism. Polymerase chain reaction microdeletion analysis was done in 140 cytogenetically normal cases. Of the 140 cases, 8 showed deletion of at least one of the sequence-tagged site markers. Review of literature has shown that the overall frequency of microdeletions varies from 1 to 55%. In the present study, the frequency of microdeletion was 5.8%, and deletions were identified in cases with undescended testis and varicocele and cases with bilateral severe testiculopathy.

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

“…30 normozoospermic cases of unexplained infertility have also been screened. The criteria for selection of patients and controls have been detailed previously [1,9,10]. For data analysis, the patients were grouped based on their seminal parameters viz severe oligozoospermia (SOAS, ≤5×10 6 million spermatozoa/mL of ejaculate), oligozoospermia (<15×10 6 million spermatozoa/mL of ejaculate), azoospermia (no spermatozoa in ejaculate).…”

“…Biplex PCR for SRY (PCR positive control) along with one pair of each STS primer was performed essentially as described previously [1,9,10]. All reactions included a fertile male control sample, a female sample and a negative (water) control.…”

Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey

“…Male infertility can be caused by a variety of factors, such as infection, varicose, endocrine disorders, spermatic duct obstruction, antisperm antibodies, cryptorchidism, retrograde ejaculation, systemic diseases, testicular cancer, testicular trauma, etc. Apart from these, in 30-40% of male infertile cases that are referred to as idiopathic, genetic abnormality is suspected [4][5][6][7][8][9].…”

“…Male infertility with genetic factors might be the result of carriers of chromosomal abnormality and/or Y chromosomal microdeletions within the Yq11 region, where the genes that control spermatogenesis, known as AZF, are located [1][2][3][4][7][8][9][10][11]. The incidence of cytogenetic abnormality has been estimated as 2.1 to 28.4% in infertile men and only 0.7-1% in the general male population [5,8,[12][13][14].…”

“…Somatic chromosomal anomalies in the infertile male may be numerical or structural and involve sex chromosomes (e.g., 47,XXY) or autosomes (e.g., balanced Robertsonian translocations) [3-5, 8, 12-14]. Approximately 5-10% of oligozoospermic cases and 15-20% of azoospermic cases harbor genetic abnormalities [9].…”