MEHP impairs male reproductive function through the lipid metabolism pathway: Evidence from in vitro human immature testis culture.

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used industrial plasticizer whose main metabolite in the body is mono-(2-ethylhexyl) phthalate (MEHP). The reproductive toxicity of DEHP and MEHP has been documented in some studies. However, precise mechanisms remain unclear, and most research has focused on animal models. In this study, an in vitro culture system of immature human testicular tissue was employed to explore the etiological link between MEHP and developmental toxicity in immature human testes. The examination of micro-morphology, subcellular structure and testosterone secretion demonstrated that immature human testicular tissue could grow best at the temperature of 34 °C in this in vitro culture system. MEHP exposure damaged organelles, reduced testosterone secretion, disrupted oxidative stress and autophagy expression levels. Transcriptome sequencing revealed that differentially expressed genes (DEGs) were mainly associated with lipid metabolism pathways, which indicated the key role of DEGs in MEHP-induced reproductive toxicity. In the current study, the toxicological mechanisms of MEHP were investigated using an in vitro model of immature human testicular tissue. The lipid metabolism pathway could be a critical molecular pathway involved. This study offers a theoretical basis for understanding toxic damage from environmental toxins.