Mono-butyl phthalate-induced mouse testis injury is associated with oxidative stress and down-regulated expression of <i>Sox9</i> and <i>Dazl </i>

Abstract

-Mono-butyl phthalate (MBP) has reproductive toxicity but the related mechanisms have not been fully elucidated in vivo. We exposed male Balb/c mice to MBP by gavage at doses of 0, 25, 50, 100, 200 mg/kg for 14 days, and then evaluated the testicular alterations at the histological and molecular levels. MBP reduced mouse sperm count along with sperm malformation and seminiferous tubule degeneration in a dose-dependent manner. MBP dosed at 200 mg/kg significantly increased reactive oxygen species and malondialdehyde content in mouse testes. High doses of MBP (200 mg/kg) also significantly reduced mRNA expressions of testis growth and function related genes (Sox9 and Dazl). Our findings suggest that oxidative stress and down-regulated expression of Sox9 and Dazl may play important roles in MBP-induced testis injury.

All-trans Retinoic Acid Disrupts Development in Ex Vivo Cultured Fetal Rat Testes. II: Modulation of Mono-(2-ethylhexyl) Phthalate Toxicity

“…This hypothesis is consistent with the interactive effects of ATRA and MEHP on testicular development and function observed in this study. This is also consistent with recent observations that phthalate exposure alters expression of sex determination genes, including Sry, Sox9, and Dazl (Du et al, 2017;Wang et al, 2016), as well as research on the central role of the transcription factor COUP-TFII in both the response to RA and phthalates and in regression of the male reproductive tract (Jorgensen et al, 2015;Zhao et al, 2017). Alteration of RA signaling by phthalates during development would also potentially be consistent with observations of teratogenic effects in some phthalate studies (Gray et al, 2016;Ungewitter et al, 2017).…”

“…oppose the seminiferous cord disorganizing effects of ATRA (Figure 3) presents significant evidence that altered seminiferous cord development is a significant component of the fetal testis toxicity of phthalates, which may be directly mediated by effects on Sertoli or peritubular myoid cells. This mechanism is consistent with recent publications that have argued that phthalates disrupt signaling for sex determination in the testis by disrupting expression of sex determination factors, such as Sry and Sox9 (Du et al, 2017;Wang et al, 2015Wang et al, , 2016.…”

Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility

“…From the preceding discussion, it is apparent that acute and/or chronic exposure to a variety of external or internal factors can trigger the overproduction of ROS and reduce antioxidant defenses within the male reproductive tract, thus propagating an OS cascade and resulting in LPO (summarized in Figure 1). causal agent responsible for elevated levels of apoptosis among developing germ cells, defects in sperm morphology and impaired sperm function in mice treated with industrial contaminants used in the production of plastics, such as bisphenol-A [63], mono-butyl phthalate [64] and other related compounds [65]. This spectrum of deleterious OS-related effects extends to other forms of chemical exposure including those associated with excessive alcohol consumption or cigarette smoking.…”