FIG. 9.

A working model of MEHP-induced MMP2 activation and its influence on junctional complexes in the serminiferous epithelium. First, MEHP exposure causes a decrease in Sertoli cell TIMP2 expression, which allows for MMP2 activation in the seminiferous tubules. Second, activated MMP2 leads to the remodeling of tight junctions between adjacent Sertoli cells by multiple mechanisms. Third, activated MMP2 directly cleaves laminin-γ3 in order to break laminin/integrin complex at the ectoplasmic specialization between Sertoli cells and spermatids. Disruption of ectoplasmic specialization as well as remodeling of tight junctions allows for the premature detachment of germ cells in the seminiferous epithelium in response to MEHP exposure.