Hypoxia Inducible Factor 1 Alpha and Matrix Metalloproteinase-9 in Dysfunctional Uterine Bleeding

Abstract

Introduction: Dysfunctional Uterine Bleeding (DUB) is prevalent in 10-15% of gynaecological patients. Matrix metallopeptidase-9 (MMP-9) expression is stimulated by reduced oxygen levels in a highly aggressive, metastatic breast cancer cell line, although MMP-2 expression is unaffected. Under hypoxic conditions, Hypoxia Inducible Factor 1 Alpha (HIF-1α) rapidly accumulates and transactivates hundreds of genes, including angiogenic growth factors as well as receptors. Aim: To compare and estimate the serum HIF-1alpha, serum MMP-9 in ultrasonographically proven DUB patients and in controls with normal menstruation. Materials and Methods: This case-control study was conducted in Department of Biochemistry at Heritage Institute of Medical Sciences, Varanasi, Uttar Pradesh, India, from July 2020 to November 2021. A random venous blood sample (4 mL) was drawn from the DUB cases and controls into a sterile red topped vacutainer which was allowed to clot for 30 minutes. The sample was centrifuged and the serum was separated and analysed for desired parameters. Serum HIF-1α and MMP-9 was estimated by using sandwich Enzyme Linked Immunosorbent Assay (ELISA) method. Student’s t test was used for comparison between the variables and pearson’s correlation test was used to assess the correlation between the parameters. Results: The mean age of controls was 33.9±7.10 years (N=40) compared to cases where it was 38.8±5.32 years (N=40). Serum HIF-1α showed significantly elevated levels of median in DUB cases (1.16 ng/mL) compared to normal control group (0.28 ng/ mL, p-value=0.04). Mean serum levels of MMP-9 significantly decreased in DUB cases as compared to normal control group (34,142±19,043, 61,500±16,169 respectively, p-value=0.003). Presence of hypoxia leading to HIF-1α and MMP-9 formation plays a role in endometrial thickness and angiogenesis leading to various signs and symptoms of DUB. The present study did not find any correlation between MMP-9 and endometrial thickness as well as HIF-1α and endometrial thickness in DUB cases and controls. There was significant low positive correlation between serum MMP-9 and HIF-1α in DUB cases (r-value=0.423, p-value <0.05). Conclusion: Elevated levels of HIF-1α and decreased levels of MMP-9 was observed in DUB cases. No correlation was found between MMP-9 and endometrial thickness as well as HIF-1α and endometrial thickness in DUB cases and controls. Hence, whether this can be used for diagnostic and therapeutic prospects needs to be further studied.