Asper Biogene – genetic testing company

Approximately 5% of infertile men and 15% of men with azoospermia have infertility due to chromosomal anomalies. The most frequent reason of male factor infertility (MFI) associated with an abnormal set of sex chromosomes is Klinefelter syndrome (47XXY), which occurs in 5% of oligozoospermic men and in 10% of azoospermic men.

Structural changes in sex chromosomes are most frequently caused by the microdeletions of genetic material in regions of the Y chromosome, called azoospermia factors AZFa, AZFb and AZFc. Microdeletions of the Y chromosome affect 10–15% men with non-obstructive azoospermia and men with severe oligozoospermia.

Many reproduction-related genes that are required in functional spermatogenesis are located in autosomal chromosomes. Mutations in these genes may lead to reduction in sperm count and impairment in functional capability. Mutations in the CFTR gene cause congenital bilateral absence of the vas deferens (CBAVD) and consequent obstructive azoospermia. CBAVD is the cause of approximately 1–2% of male infertility.

Mutations of GNRHR (gonadotropin-releasing hormone receptor) gene may result in changes of sexual differentiation. GNHR receptors are the primary site of action of GNRH – a key neuroregulator of the reproductive process.

Mutations in development and differentiation-related gene INSL3 occur in 5% of men with cryptorchidism. RXFP2 gene (also known as LGR8) product is the cellular receptor for INSL3. INSL3-LGR8 mutations are frequently associated with human cryptorchidism.

PRM1, PMR2 and PRM3 genes belong to the promatine locus that is associated with spermatogenesis and mutations in these genes have been shown to be a possible cause of azoospermia or oligospermia as well as disruptions in the functional ability of sperm.

PRDM9 gene has been associated with azoospermia by meiotic arrest.

DDX25 gene is a gonadotropin-regulated testicular RNA helicase that is essential for spermatid development and spermatogenesis.

ESR2 has also been shown to have a role in spermatogenesis.

Mutations in TEKT2 cause impaired motility of the sperm.

FSHB gene is essential for Sertoli cell proliferation and maintenance of sperm quality in the testes.

RBMXL2 is a highly expressed protein in germ cells which primarily localizes to the nuclei of meiotic spermatocytes. Studies in mice suggest that the disruption of RBMXL2 activity inhibits the formation of functional sperm.

NLPR14 is exclusively expressed in human testes and mutations in NLPR14 have been found in patients with spermatogenetic failure.

USP26 is also expressed in testes and might be involved in spermatogenesis by playing a role in sperm motility or have an effect on sperm count.

Infertile patients who carried a mutation in UTP14C gene presented with nonobstructive azoospermia or with severe oligospermia.

DNAI1, DNAH5 and DNAH11 genes have been linked to primary ciliary dyskinesia that can cause abnormal sperm motility.