The role of MMP9 C-1562T and MMP2 G1575A genetic variants in male infertility: review article

Infertility as a vital process in human reproduction involves many couples worldwide. Although many genetic causes of infertility are known, the genetic basis of infertility in men is largely unknown. Therefore, the identification of genetic biomarkers in this field is important and genetic polymorphisms in key genes of the spermatogenesis pathway can be valuable biomarkers in this field. Gene's polymorphisms with specific genetic background and/or environmental factors can lead to the dysfunction in testicular function or the process of sperm production. Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that play an important role in extracellular matrix remodeling by activating gelatinases, collagenases, and proteolytic enzymes. These enzymes are essential for the regulation of cellular connections in the testis. Extracellular matrix degradation and connective tissue remodeling are important structural changes in germ cell migration that are controlled through important genes, including MMPs and their biological inhibitors. Given the important role of MMPs in the structural and functional characteristics of reproductive organs, genetic polymorphisms in MMP genes are significant because they can influence gene transcription and the biological function of proteins. Studies have shown that matrix metalloproteinases are involved in the degradation of extracellular matrix and play an important role in the process of spermatogenesis and sperm quality. This review article aims to evaluate the role of two common, functional MMP2 G1575A and MMP9 C-1562T polymorphisms in male infertility. The findings indicate that polymorphisms of MMP2 G1575A and MMP9 C-1562T can affect gene transcription, protein level, and enzymatic activity, and also, these variants can be as one of the genetic causes in male infertility among different ethnic populations. Therefore, identifying these molecular changes can help to adopt appropriates therapeutic and diagnostic measures as well as guide therapeutic approaches to intelligent therapies. To achieve a definitive conclusion and confirm the association of these polymorphisms with male infertility, evaluations of gene-gene and gene-environment interactions can be important for larger sample sizes of different ethnicities.