Male reproductive toxicity of di(2-ethylhexyl) phthalate: data from a rat model

Di(2-ethylhexyl) phthalate, the most common plasticizer, normally enters the body by ingestion, inhalation, or dermal absorption and has the potential to achieve toxic effects through various intracellular signaling pathways. The antiandrogenic effects of di(2-ethylhexyl) phthalate and the activation of estrogen receptors are largely responsible for the toxic effects on the reproductive system. The histomorphological examinations of the testes in pre-pubertal and adult rats, which were treated with di(2-ethylhexyl) phthalate, showed numerous changes in the function and the structure of the seminiferous tubules, Sertoli, and Leydig cells. Di(2-ethylhexyl) phthalate disturbs spermatogenesis and steroidogenesis by disabling the blood-testis barrier and reduces the thickness of the seminiferous tubules' epithelia, their diameters, and the number of germ cell layers. In consequence, sperm production is reduced and the degree of damage to the motility and reduction of the number of spermatozoa is greater if di(2-ethylhexyl) phthalate is combined with bisphenol A. Due to oxidative stress, peroxisome proliferator-activated receptors, and its effects on testosterone production, the testosterone levels are reduced. Polyphenols such as mangiferin, isoflavones, and other antioxidants may mitigate these effects.