Reproduction Abstracts

Introduction: Defective sperm–egg recognition is recognised as one of the major causes of failed fertilization in IVF programs. Our recent findings have revealed that such defects may be linked to the molecular chaperone, heat shock protein A2 (HSPA2), due to its ability to facilitate the formation of multimeric zona pellucida (ZP)-receptor complexes on the surface of human spermatozoa. This study aimed to examine the impact of oxidative stress on the formation of these ZP receptor complexes.

Materials and method: For the purpose of this study, low levels of oxidative stress were induced in populations of human spermatozoa through treatment with 4-hydroxynonenal (4HNE) or hydrogen peroxide (H₂O₂).

Results and discussion: The surface expression of the predominant HSPA2 complex containing the putative ZP receptors sperm adhesion molecule 1 (SPAM1) and arylsulfatase A (ARSA) was found to be significantly disrupted by both 4HNE and H₂O₂ treatment. Furthermore, the ability of sperm to interact with ZP (P<0.01) and undergo an induced acrosome reaction (P<0.05) was also severely compromised. Upon investigating the mechanism of action it was demonstrated that oxidative stress targeted HSPA2 for covalent modification by 4HNE. From these data we infer that the adduction of HSPA2 by 4HNE may cause attenuation of its chaperone activity and a subsequent deregulation of the coordinated surface expression of SPAM1 and ARSA. The perturbation of this complex may thereby contribute to the observed loss of ZP binding ability and supports a key role for this complex in the initial tethering of human spermatozoa to the ZP.