Related Experiment Video
Updated: Mar 18, 2026
Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
Published on: March 1, 2019
MMP2, MMP9 and TIMP2 polymorphisms affect sperm parameters but not fertility in Polish males
M Kurzawski1, M Kaczmarek1, M Kłysz1
1Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland.
Abstract:
Proper function of the blood-testis barrier is pivotal to spermatogenesis. Synchronised action of matrix metalloproteinases (MMP) and their inhibitors (TIMP) is mandatory to maintain dynamic balance of the barrier. Therefore, the association of functional genetic variants of MMP-2, MMP-9 and TIMP-2 and male infertility was studied. A total of 416 infertile males and 421 healthy subjects were genotyped for 7 SNPs within MMP2, MMP9 and TIMP2 genes, along with the assessment of semen parameters (concentration, motility and morphology of spermatozoa). No association was observed between the studied genotypes and male infertility. However, higher sperm concentration was associated with TIMP2 rs8080623 C and rs2277698 T variants among infertile men, and with MMP9 rs17576 A minor allele in controls (p < .05). TIMP2 rs9900972 T and rs2277698 T allele were associated with higher percentage of morphologically normal spermatozoa among controls. MMP2 rs2285053 TT homozygous infertile patients presented higher percentage of spermatozoa displaying nonprogressive motility. Haplotype analysis revealed strong linkage disequilibrium between the studied loci (5 of 8 possible TIMP2 haplotypes, and 3 of 4 possible MMP2 and MMP9 were found). None of the haplotypes showed association with infertility. This study results suggest an association between MMP9 and TIMP2 SNPs with sperm parameters, but not infertility.
Insights
Genetic variants in matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes were studied for male infertility. While no direct link to infertility was found, specific MMP9 and TIMP2 gene variants influenced sperm concentration and morphology.
Area of Science:
- Reproductive Biology
- Genetics
- Andrology
Background:
- The blood-testis barrier's integrity is crucial for spermatogenesis, requiring balanced activity of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).
- Understanding the genetic basis of male infertility involves examining functional variants in genes related to barrier maintenance.
Purpose of the Study:
- To investigate the association between functional genetic variants (SNPs) in MMP2, MMP9, and TIMP2 genes and male infertility.
- To assess the impact of these genetic variants on semen parameters, including sperm concentration, motility, and morphology.
Main Methods:
- Genotyping of 7 single nucleotide polymorphisms (SNPs) within MMP2, MMP9, and TIMP2 genes in 416 infertile males and 421 healthy controls.
- Analysis of semen parameters (sperm concentration, motility, morphology) in relation to genotypes.
- Haplotype analysis to examine linkage disequilibrium between studied loci.
Main Results:
- No significant association was found between the studied MMP2, MMP9, and TIMP2 genotypes and male infertility.
- Specific TIMP2 variants (rs8080623 C, rs2277698 T) and an MMP9 variant (rs17576 A) were associated with higher sperm concentration in infertile men and controls, respectively.
- TIMP2 variants (rs9900972 T, rs2277698 T) correlated with increased morphologically normal spermatozoa in controls, while MMP2 rs2285053 TT genotype was linked to nonprogressive sperm motility in infertile patients.
- Haplotype analysis revealed linkage disequilibrium but no association with infertility.
Conclusions:
- Single nucleotide polymorphisms in MMP9 and TIMP2 genes are associated with specific sperm parameters, but not directly with male infertility.
- These findings suggest a role for MMP and TIMP genetic variations in modulating sperm quality rather than causing infertility itself.
Related Concept Videos
01:23Infertility in Males
01:41Spermatogenesis