Disrupted hyaluronan binding protein 1 (HABP1) expression: one of the key mediator for ovarian dysfunction in polycystic ovary rat

Abstract

Proper follicular development is crucial for cumulus-oocyte complex (COC) maturation, ovulation and luteinisation. All these ovarian processes are regulated by finely tuned rapid tissue remodeling that involves hyaluronan and interconnecting hyaladherins-rich extracellular matrix synthesis and its breakdown by various proteinase systems like matrix metalloproteinase (MMP). Disrupted tissue remodeling machinery can result into pathophysiologies like atretic follicular cysts formation in polycystic ovary syndrome (PCOS). In present study, we employ superovulated (SO) and polycystic ovary (PCO) rat models and demonstrate that on contrary to SO, PCO rat ovary illustrates abnormal follicular morphology with differential levels of various ovarian factors [like HA (hyaluronan), TSG-6 (TNF-α-stimulated gene/protein 6), PTX-3 (pentraxin-3), HABP1 (hyaluronan binding protein 1), MMP2 (matrix metalloproteinase), MT1-MMP (membrane type 1-matrix metalloproteinase) and COX2 (Cyclooxygenase-2)] along with hyperactivities of gelatinases (like MMP9 and -2). Besides cultured COC expansion is blocked by anti-HABP1 antibody treatment showing reduced HABP1 expression. Overall, as MT1-MMP has inverse relation with HABP1 level and direct effect on MMP2 activity, the observations from current in vivo and in vitro studies indicate that disrupted ovarian HABP1 along with concurrent altered expression and hyperactivation of related MMPs can lead to abnormal follicular maturation resulting into ovarian dysfunction in PCO rat.