Figure 4
A schematic mechanism on the effects of phthalate esters and organochlorines on testosterone and sperm quality.
A. Steroidogenesis. EDCs can inhibit the synthesis of testosterone through direct pathways including cholesterol, StAR, 3β-HSD, CYP 17 and 17β-HSD, or indirect pathways including the binding of LH to LH receptor and PPARγ, PKA and StAR, or through FSH receptor, or the binding of testosterone to ABP or AR. In addition, EDCs can increase the AROM activity, which converts testosterone to estrogen, resulting in the decrease in testosterone. B. Spermatogenesis. EDCs may affect spermatogenesis through the apoptosis of spermatocytes, ROS production, or disrupting BTB integrity via the activation of PI3K/FAK or PI3K/Akt and MAPK/ERK signaling pathways. C. DNA damage and DNA methylation. CpG islands may be possible mechanisms of EDC-induced testicular toxicity and sperm quality. LHR, luteinizing hormone receptor; PPARγ, peroxisome proliferator activated receptor gamma; PKA, protein kinase A; CREB, cAMP response element; StAR, steroidogenic acute regulatory protein; TSPO, translocator protein; 3β-HSD, 3β hydroxysteroid; CYP 17, Cytochrome P450 17; 17β-HSD, 17β hydroxysteroid; AROM, cytochrome P450 aromatase; ROS, reactive oxygen species; AR, androgen receptor; ER, estrogen receptor; FSH, follicle stimulating hormone; ABP, androgen binding protein; PI3K, phosphatidylinositol 3 kinase; FAK, focal adhesion kinase; MAPK, mitogen activated protein kinase; ERK, extracellular regulated protein kinases; BTB, blood–testis barrier.
