Investigation of Protamine Genes (PRM1, PRM2) Polymorphism and Its Impact on Sperm Toroid Integrity in Males from Ahmedabad (India)

Aim: Although infertility rates have been escalating in the past few years, there are very few studies directed towards its investigation, especially for males in the region of Ahmedabad, India. Hence the present study was aimed at identifying polymorphisms in the protamine genes (PRM1, PRM2) and their possible impact on sperm chromatin, in order to determine molecular changes which could impede sperm fertilizing ability.

Methodology: Infertile patients (Group II; n=23) with history of failure of in-vivo and in-vitro fertilization were included in the study. Normal, fertile age-matched men were selected as controls (Group I; n=25). Sperm Toroid Integrity (STI) assays was used to analyze Protamine-DNA binding efficiency. Sequencing was carried out for the protamine genes "PRM1 and PRM2" to screen for relevant single nucleotide polymorphisms (SNPs) that could alter the protein structure and its function of compact DNA binding, possibly impairing sperm fertilizing potential.

Results: A significantly higher percentage of protamine-DNA dissociation and partial toroid disruption was observed in the infertile cases. However, sequencing yielded only a single distinct SNP at nucleotide 239 (rs737008) in PRM1 gene.

Conclusion: The study revealed therefore that although the sequence of PRM genes and the resultant protamine proteins may not be altered, a loose protamine-DNA association and a disturbed toroid assemblage could render the DNA vulnerable to external pressures, leading to poor sperm function.