Effects of chronic dichlorodiphenyldichloroethylene exposure on testosterone secretion and steroidogenic pathway in the male gonad.

Endocrine disrupting chemicals are present in the environment and/or in consumer products. These agents have the capacity to mimic and/or antagonize endogenous hormones and thus perturb the endocrine axis. The male reproductive tract expresses steroid hormone (androgen and estrogen) receptors at high levels and is a major target for endocrine disrupting chemicals. In this study, Long-Evans male rats were exposed to dichlorodiphenyldichloroethylene, a metabolite of dichlorodiphenyltrichloroethane and a chemical present in the environment, in drinking water at 0.1 and 10 µg/L for 4 weeks. At the end of exposure, we measured steroid hormone secretion and analyzed steroidogenic proteins, including 17ß-hydroxysteroid dehydrogenase, 3ß-hydroxysteroid dehydrogenase, steroidogenic acute regulatory protein, aromatase, and the LH receptor. We also analyzed Leydig cell apoptosis (poly-(ADP-ribose) polymerase) and caspase-3 in the testes. Testicular testosterone (T) and 17ß-estradiol (E2) were both affected by exposure to dichlorodiphenyldichloroethylene by displaying altered steroidogenic enzyme expression. Dichlorodiphenyldichloroethylene exposure also increased the expression of enzymes mediating the pathway for programmed cell death, including caspase 3, pro-caspase 3, PARP, and cleaved PARP. Altogether, the present results demonstrate that dichlorodiphenyldichloroethylene directly and/or indirectly can target specific proteins involved in steroid hormone production in the male gonad and suggest that exposure to environmentally relevant dichlorodiphenyldichloroethylene levels has implications for male reproductive development and function.

Effects of different DDE exposure paradigms on testicular steroid hormone secretion and hepatic oxidative stress in male Long-Evans rats.

Chronic exposure to low doses of anthropogenic chemicals in the environment continues to be a major health issue. Due to concerns about the effects in humans and wildlife, use of persistent organic pollutants, such as dichlorodiphenyltrichloroethane (DDT), is prohibited. However, their ubiquitous nature and persistence allows them to remain in the environment at low levels for decades. Dichlorodiphenyldichloroethylene (DDE) is the most persistent metabolite of DDT and has been shown to cause hepatotoxicity, nephrotoxicity, hormonal disorders, and induce oxidative stress in many organisms. Although the effects of acute exposure to DDT and its metabolite DDE have been extensively studied, the chronic effects of sub-lethal DDE exposure at levels comparable to those found in the environment have not been well documented. Long-Evans male rats were used to determine the effect of relatively chronic and short term DDE (doses ranged from 0.001 to 100 µg/L) exposure on endocrine function and oxidative stress at different developmental time points. We found that circulating serum testosterone (T) levels were significantly decreased and T secretion in testicular explants were significantly influenced in a dose dependent manner in both pre-pubertal and pubertal male rats after DDE exposure, with pubertal rats being the most affected contrary to our original prediction. Additionally, exposure to DDE increased expression of protein oxidation indicating a possible increase in cellular damage caused by oxidative stress. This study suggests that chronic exposures to environmentally relevant levels of DDE affected testicular function and decreased T secretion with implications for reproductive capacity.

Chronic Exposure to Environmental DDT/DDE in 2 Species of Small Rodents: Measures of Contaminant Load, Immune Dysfunction, and Oxidative Stress.

Persistent contaminants are ubiquitous in our water and soil, and thus chronic exposure to environmentally relevant levels of these contaminants may pose a risk to humans and wildlife. Two species of small mammals (deer mouse, Peromyscus maniculatus and cotton rat, Sigmodon hispidus) were collected from historically dichlorodiphenyltrichloroethane (DDT)-contaminated and reference areas at the Redstone Arsenal (Huntsville, AL, USA), a US Environmental Protection Agency (USEPA)-designated Superfund site. Soil samples taken concurrently with mammal collection from the DDT abatement site exhibited DDT and dichlorodiphenyldichloroethylene (DDE) levels >1 ppm (USEPA total threshold limit concentration for DDT and DDE <1 ppm), whereas soil samples from the reference area had undetectable levels. Liver samples from individuals of both species collected in the contaminated areas also had significantly elevated DDT/DDE levels, with P. maniculatus averaging an approximately 20× greater load than that documented for S. hispidus. Both rodent species collected from the contaminated site had significantly lower total leukocyte counts and total differential blood cell counts (p = 0.01 and p = 0.04, respectively) than those collected from the nearby (~7000-m) reference site. Cellular stress indices also trended higher in both species, suggesting a potential for chronic exposure to DDT to act as a mediator of oxidative damage. The present study provides support to the idea that environmental exposure to low levels of contaminants can cause physiological consequences that may influence immune responsiveness and initiate cellular stress in resident mammals. Environ Toxicol Chem 2021;40:1619-1629. © 2021 SETAC.