Impaired human sperm-zona pellucida receptor complex function in the presence of low levels of oxidative stress (#36)
Despite our sophisticated knowledge of sperm function, a significant proportion of men attending IVF clinics have unexplained infertility. In the absence of an observable 'infertile' phenotype, defective sperm-egg recognition has been suggested as one of the major causes of low fertilisation rates in IVF programs. Recent findings have revealed that molecular chaperones may facilitate the formation of multimeric zona pellucida (ZP)-receptor complexes on the surface of mammalian sperm during their capacitation in the female reproductive tract. Given the well established link between oxidative stress and male-factor infertility, in this study we sought to determine whether oxidative stress impacts upon the formation of chaperone-laden complexes and hence the acquisition of sperm fertilising potential during capacitation.
For the purpose of this study, low levels of oxidative stress were induced in populations of non-capacitated human spermatozoa through treatment with 4-hydroxynonenal (4HNE) or hydrogen peroxide (H2O2) after which sperm were incubated under capacitating conditions. Among the early stage correlates of the capacitation process it was found that membrane fluidisation and lipid raft redistribution were able to proceed at levels similar to that of untreated, capacitated sperm. However, the ability of sperm to interact with human ZP (p<0.01) and undergo an induced acrosome reaction (p<0.05) was severely compromised. Furthermore, the coordination of a chaperone laden complex containing Heat shock protein A2 (HSPA2), and the putative ZP receptors Sperm adhesion molecule 1 (SPAM1) and Arylsulfatase A (ARSA) was disrupted in the presence of both 4HNE and H2O2. Specifically, the capacitation-dependent surface expression of ARSA was significantly reduced (p<0.02). From these data we infer that sperm placed in an environment of oxidative stress may be unable to complete the process of capacitation and therefore assemble the ZP receptor complexes necessary for their interaction with oocytes in vitro.