Hyaluronan binding protein-1: a modulator of sperm-oocyte interaction

Abstract

Hyaluronan (HA), a complex glycosaminoglycan, is an important component in reproductive fluids and regulates several reproductive processes. It is thought that the multifaceted biological function of HA is mediated through hyaladherin family protein that binds with HA. We have reported a novel glycoprotein from human that has specific affinity towards hyaluronan, referred to as Hyaluronan Binding Protein-1 (HABP1, Ac. No. NP-001203) and is localized on human chromosome 17 p13.3. Sequence analysis of this gene has further revealed that HABP1 is synthesized as a precursor protein of 282 amino acids which undergoes a post-translational modification to give rise to the mature form of 209 amino acids by proteolytic cleavage of 73 amino acids at the N-terminal. The localization of mature HABP1 in several organs including the sperm surface and its involvement in fertilization have already been demonstrated. Enhanced phosphorylation of HABP1 in motile spermatozoa suggests its involvement in cellular signalling. Though only the mature form of HABP1 is detected in somatic tissues, the precursor form of HABP1 was detected in testicular tubules in a stage-specific manner in pachytene and round spermatids. To study the role of HABP1 in the fertilization process, we have shown the absence of mature HABP1 in cryptorchidic rats testes and an accumulation of the precursor form of HABP1 in giant cells, generated in infertile cryptorchidic rats. The loss of HABP1 from the sperm surface of a patient with very low sperm motility and the absence of the proprotein form of HABP1 in pachytene and round spermatids from testicular biopsy material with spermatogenic arrest, suggests that male infertility may be associated with the level of HABP1 on spermatozoa. In order to examine the role of HABP1 in sperm-oocyte interaction, we found that the number of spermatozoa bound to an oocyte was reduced significantly in the presence of D-mannosylated albumin, the universal blocker of sperm-oocyte interaction, and that this effect could be reversed by the addition of purified recombinant HABP1. In continuation, we have used spermatozoa of a patient, who had failed in IVF: the spermatozoa were incubated with HABP1 containing IVF medium for 2 hrs, then washed and allowed them to interact with the oocyte. The fertilized egg thus devloped up to the 16 cell stage, suggesting that HABP1 can modulate the sperm-oocyte interaction, even when sub-fertile spermatozoa are used.