Environmental toxicants and male reproductive function

Abstract

environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine disruptors. in utero, perinatal or neonatal exposure of BPA to rats affect the male reproductive function, such as the blood-testis barrier (BTB) integrity. This effect of BPA on BTB integrity in immature rats is likely mediated via a loss of gap junction function at the BTB, failing to coordinate tight junction and anchoring junction function at the site to maintain the immunological barrier integrity. This in turn activates the extracellular signal-regulated kinases 1/2 (erk1/2) downstream and an increase in protein endocytosis, destabilizing the BTB. The cadmium-induced disruption of testicular dysfunction is mediated initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK) complex at the BTB, causing redistribution of proteins at the SertoliSertoli cell interface, leading to the BTB disruption. The damaging effects of these toxicants to testicular function are mediated by mitogen-activated protein kinases (MAPK) downstream, which in turn perturbs the actin bundling and accelerates the actin-branching activity, causing disruption of the Sertoli cell tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion at the apical ectoplasmic specialization (apical eS, a testis-specific anchoring junction type) that leads to premature release of germ cells from the testis. However, the use of specific inhibitors against MAPK was shown to block or delay the cadmium-induced testicular injury, such as BTB disruption and germ cell loss. These findings suggest that there may be a common downstream p38 and/or erk1/2 MAPK-based signaling pathway involving polarity proteins and actin regulators that is shared between different toxicants that induce male reproductive dysfunction. As such, the use of inhibitors and/or antagonists against specific MAPKs can possibly be used to "manage" the illnesses caused by these toxicants and/or "protect" industrial workers being exposed to high levels of these toxicants in their work environment.

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

“…Environmental toxins can impair the viability and function of Sertoli cells, inducing BTB disruption. [109][110][111] Our findings demonstrate that ZO-1 and Cx43 were targeted by AgNPs, as evidenced by the decreased level of their mRNA in TM4 cells exposed to AgNPs, whereas Ocln-11 did not show significant changes ( Figure 10B). Vimentin expression is considered an indicator of the early effects of testicular toxins.…”

Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury

“…Essentially, the dynamic nature of spermatogenesis requires AJs to act rapidly to extracellular stimuli in order to permit a timely passage of developing germ cells across the seminiferous epithelium from the basal to the adluminal compartment (Yan et al 2008). Therefore, the half-life of AJs component proteins is usually short and thereby Sertoli germ cell contacts are subject to extensive alteration and remodeling (Cheng et al 2011). In addition, EGF signaling has been identified as one of the earliest signal transduction events occurring near the cell membrane in response to different stress conditions (Cai et al 1998, Zhang & Jope 1999, Murshid et al 2011.…”

Adverse effects of bisphenol A on the testicular parenchyma of zebrafish revealed using histomorphological methods

“…Most of the samples exhibited an alteration in their testicular structure with an extensive degeneration in the testes, a major reduction in the tubules of the spermatogenic lines, and with a local atrophy of the germinal epithelium, and remains of germinal cells and inflammatory processes inside the tubules (Mandich et al 2007;Al-Sakran et al 2016;Li et al 2016). There are other studies in which it was observed that the alteration in the blood-testis barrier at 200µM perturbed the tight junction of sustentacular cells (Cheng et al 2011). This differs from what was observed in rats after exposure to 20 and 100 mg/kg of BPA, where there were no adverse effects on the testicular morphology compared to the control (Nakamura et al 2010).…”