Supervisors info:
Μαυρογιάννη Δέσποινα, Ε.ΔΙ.Π., Ιατρική Σχολή, ΕΚΠΑ
Δρακάκης Πέτρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σταύρος Σοφοκλής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
The aim of this control-case study is to investigate if there is association between the rs17576 polymorphism in Matrix-Metalloproteinase 9 (MMP-9) gene and male infertility. Infertility is a clinical problem that affects many couples and 50% of these cases are caused by male factor. Male infertility is a complex phenomenon and is usually influenced by many environmental and genetic factors. The semen comprises components that affect sperm fertilizing ability and have thus far remained little explored. These components are referred to biochemical parameters of the seminal plasma secreted by the testis, the seminiferous tubules and the prostate gland, such as metalloproteinases.
Matrix Metalloproteinases (MMPs) are a family of zinc-dependent enzymes that are involved in matrix degradation and remodelling. They participate in a number of physiological processes, such as ovulation and fertilization. Reproductive organs undergo major alterations in their structural and functional properties throughout adult life and MMPs contribute to these modifications. Accumulating evidence has shown that MMPs impact male fertility due to their involvement in the development of reproductive organs, in spermatogenesis and in fertilization.
MMP-9 belongs to gelatinases, a subtype of metalloproteinases, which are involved in the degradation of collagen type IV and gelatine. It presents in the tail of the sperm and plays a role in sperm generation and differentiation. Single nucleotide polymorphisms in code or non-code regions of MMP-9's gene influence its expression and alter enzyme’s activity, affecting fertility. The rs17576 polymorphism is located at exon 6 of MMP-9 gene and results in adenine’s replacement with guanine. Studies have related rs17576 with prostate cancer and inflammation. Although, it remains unclear if rs17576 affects sperm parameters and subsequently male infertility.
In order to investigate this question, they were used 114 sperm samples in total. The control group contained 61 sperm samples from fertile men, while the case group consisted of 53 samples from infertile men according to WHO guidelines. DNA was extracted, amplified with polymerase-chain-reaction and incubated with BSO BI restriction enzyme, so as to detect the rs17576 polymorphism. From statistical analysis of the results, it is shown that the percentage of the normal genotype was almost the same between the fertile (52,5%) and the infertile men (49,1%). The percentage of the heterozygous genotype was higher in fertile samples (39,3%) than in infertile (32,1%) samples, while the percentage of homozygous genotype was higher in infertile group (18,9%) in comparison with the fertile one (8,2%). However, the differences in the percentage of each genotype between the fertile and the infertile men are not statistically significant, concluding that in this specific population the rs17576 polymorphism does not affect male fertility.
Keywords:
Male Infertility, SNP, rs17576, MMP-9, sperm
