Marvdasht IAU Graduate Discovers New Gene for Infertility Treatment

Wednesday, October 2, 2019 - 12:21

Arvand Akbari, PhD graduate student in Molecular Genetics and Genomics, in Marvdasht Islamic Azad University has discovered a new gene for male infertility considering Iranian ethnicity and race that can an achievement in infertility treatment.

In his interview with ISCA News Agency, Arvand Akbari stated that his PhD dissertation with the title of “ADCY10 frameshift variant leading to severe recessive asthenozoospermia and segregating with absorptive hypercalciuria” has been chosen as the top research of the year.

He declared that Iran is considered as the top country in the field of infertility treatment in the Middle East therefore, those with fertility problems, especially from the neighboring countries are coming to our country for treatment, which has been considered as the notable achievement after Islamic Revolution.

Based on the research, supported by grants from the Royan Institute, Tehran, Iran, and San Raffaele Hospital, Milan, Italy, ADCY10 encodes for soluble adenylyl cyclase (sAC), which is the predominant adenylate cyclase in sperm. It is already established that proper sAC activity and a constant supply of cAMP are crucial to sperm motility regulation, and knockout mouse models have been reported as severely asthenozoospermic.

ADCY10 is a susceptibility gene for dominant absorptive hypercalciuria (OMIM#143870); however, no ADCY10 variations have been confirmed to cause human asthenozoospermia to date.

This was a retrospective genetics study of a highly consanguineous pedigree of asthenozoospermia. The subject family was recruited in Iran in 2016. The two patients were diagnosed as asthenozoospermic through careful clinical investigations. Both patients, respective parents, and an unaffected brother were subjected to WES.

The discovered variant was validated by Sanger sequencing and segregated with the phenotype. To confirm the pathogenicity of the variant, sperm samples from both patients, 10 normozoospermic men and 10 asthenozoospermic patients not representing the variation, were treated with a cAMP analogue dissolved in human tubal fluid medium, followed by computer-assisted sperm analysis and statistical analyses.

The discovered homozygous variant occurs at 10 amino acids upstream of the ADCY10 nucleotide binding site leading to a premature termination (p.His402Argfs*41). Treatment of the patients’ sperm samples with a cell-permeable cAMP analogue resulted in a significant increase in sperm motility, indicating the pathogenic role of the variant. Moreover, absorptive hypercalciuria, segregating within the family, was also associated with the same variant following a dominant inheritance.

The finding enlarges the phenotypic spectrum associated with the ADCY10 gene, previously described as a susceptibility gene for dominant absorptive hypercalciuria.

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