In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus

Abstract

Cadmium (Cd) and arsenic (iAs) are toxic metals ubiquitously present in the environment. Both pollutants exert nonmonotonic dose responses, being mostly cytotoxic at high concentrations but mimicking estrogen (E2) effects at low doses. Xenoestrogenic activity of Cd and iAs has been demonstrated in different hormone-dependent tumor cell lines; however, their actions in vivo remain largely unknown. Here, we investigated whether in vivo administration of low doses of Cd and iAs through drinking water would display xenoestrogenic effects in the anterior pituitary gland and uterus of ovariectomized rats. Cd (1 ppm) and iAs (0.1 ppm) exposure increased the wet weight of anterior pituitary gland and uterus and induced proestrus-and estrus-like vaginal smears. Both metals stimulate cell proliferation of these tissues as they increased the expression of proliferation markers. More importantly, they augmented soluble guanylyl cyclase α1 subunit expression, which has been linked to hormone-dependent tumor progression. Also, Cd and iAs modified protein levels of full-length estrogen receptor α and its truncated variants in an E2-like manner. Anterior pituitary hormone secretion was differentially affected by both metals. Luteinizing hormone synthesis and release were strongly diminished after Cd exposure and only mildly reduced by iAs. Both metals were able to increase prolactin synthesis, although only iAs augmented serum prolactin levels. This study shows for the first time that Cd and iAs exert strong xenoestrogenic effects on anterior pituitary gland at low doses. The differences between Cd and iAs E2-like behavior indicate that other Cd-and iAs-specific mechanisms could be involved. Altogether, these results contribute to the knowledge of reproductive disorders associated with Cd and iAs environmental contamination.

Modeling Environmentally-Induced Motor Neuron Degeneration in Zebrafish

“…ALS has been associated with heavy metals that have endocrine disrupting qualities 29 , 45 , 46 . For example, metals associated with ALS such as cadmium 47 and manganese 48 have been shown to have an effect on estrogenic activity 16 . However, a similar dose of BPA as used by our group has been reported to induce apoptosis mainly in the cells of the brain and spinal cord in Xenopus laevis embryos, which did not appear to be due to BPA’s estrogenic properties 49 .…”

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

“…Current evidence supports cadmium being cytotoxic at high concentrations. At low doses cadmium mimics estrogen (E2) effects both in vitro and in vivo [149]. …”

“…At low doses arsenic acts as a xenoestrogen and modifies estrogen signaling [149]. Human populations are usually exposed through the air, drinking water, and food, with food being the main source of arsenic in a population, with some areas having naturally high levels of arsenic [162].…”

“…However, PCBs, BPA, phthalates, Cd, As or Mn, through influencing gonadotropin-releasing hormone (GnRH) regulated increases in levels of serum LH and E2, have been shown to modify the hypothalamic–pituitary-ovarian axis and they also bind to estrogen receptors [1,2,149,173]. BPA, Phthalates and metalloestrogens—Cd, As and Mn have been shown to cross the blood brain barrier [1,64,65,118,119,149,173]. Metalloestrogens, such as arsenite, cadmium, mimic the actions of physiological estrogens through binding to estrogen receptors [196,197,198].…”

Spirulina platensisameliorates arsenic-mediated uterine damage and ovarian steroidogenic disorder

“…Long term exposure of arsenic in animal models has established male and female reproductive hazards: the alteration of ovarian and testicular steroidogenesis, the disruption of ovarian and testicular tissue, and the arrestation of spermatogenesis and folliculogenesis (Shukla and Pandey 1984;Chattopadhyay and Ghosh 2010). Arsenic-contaminated drinking water has xenoestrogenic effects on the anterior pituitary gland, and anterior pituitary hormone secretion is affected by arsenic (Ronchetti et al 2016). Chronic environmental arsenic exposure in humans has been reported to cause reproductive disturbances in women (Zadorozhnaja et al 2000) including critical pregnancy, low birth weight, reduced lactation, and impetuous abortion (Ahmad et al 2001).…”