Figure 2.

Mechanisms underpinning the loss of heat shock protein A2 (HSPA2) from the spermatozoa of infertile patients. Although the mechanism(s) underpinning the selective loss of HSPA2 from the differentiating gametes of infertile patients is currently unknown, several possibilities have been raised. These include: (a) genetic mutations in the encoding Hspa2 gene, (b) epigenetic regulation of Hspa2 gene expression, and/or (c) perturbations in protein expression/stability arising from exposure of developing germ cells to oxidative stress. With regard to the latter it is possible the oxidative attack could act directly to damage the Hspa2 gene or mRNA transcript. Alternatively, the HSPA2 protein itself may be targeted for destruction following adduction by electrophilic aldehydes generated as a result of reactive oxygen species-induced lipid peroxidation. Such insults are known to lead ubiquitin (Ub)-dependent degradation via proteasomal or lysosomal pathways.