Endocrine-disrupting chemicals (EDCs) an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or can mimic the occurrence of natural hormones that damage for the balance of homeostasis. Exposure to EDCs results in damage to human health that may persist in the long term. In recent years, accumulative evidence has demonstrated that EDCs also play a pivotal role in the onset and development of myocardial fibrosis, including heart failure, hypertension and vascular stiffening. Studies indicate that EDCs plays the negative effects of the cardiovascular system, however, EDCs-induced toxicity on heart remains unclear. This review summarized EDCs-induced myocardial fibrosis, and discuss the possible mechanisms of myocardial fibrosis induced by EDCs. This paper could provide further understandings for prevention, diagnosis and treatment of myocardial fibrosis.
Endocrine Disruptors/toxicity* ; Environmental Exposure ; Environmental Pollutants ; Fibrosis ; Humans

Endocrine Disruptors ; toxicity ; Environmental Pollutants ; toxicity ; Humans ; Immune System ; drug effects

The reproductive toxicity of environmental endocrine disruptors has attracted substantial attention from researchers in recent years. Bisphenol A (BPA) is among the most prominent environmental estrogens worldwide, demonstrated to be related with the impairment of male reproductive function as well as other health problems, such as diabetes, obesity, cardiovascular diseases, and cancer. BPA acts primarily by mimicking antiandrogenic and estrogenic effects, disturbing the hypothalamic-pituitary-testicular axis and modulating gene expressions and enzyme activities in the hormone biosynthesis affecting steroids or its receptors. BPA is also involved in DNA methylation and the effects of epigenetics, resulting in dyszoospermia, oligoasthenoteratospermia/azoospermia and/or infertility in males. This review addresses the effects of BPA on male reproductive function, focusing on the mechanisms of its toxicity on spermatogenesis, semen quality, and the reproductive system.
Benzhydryl Compounds ; toxicity ; Endocrine Disruptors ; toxicity ; Endocrine System ; drug effects ; Environmental Pollutants ; toxicity ; Estrogens ; toxicity ; Humans ; Infertility, Male ; chemically induced ; Male ; Phenols ; toxicity ; Semen Analysis ; Spermatogenesis ; drug effects

BACKGROUND: Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models. METHOD: In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs. RESULTS: From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models. CONCLUSION Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.
Animals ; Benzhydryl Compounds ; toxicity ; Diethylstilbestrol ; toxicity ; Dose-Response Relationship, Drug ; Drug Interactions ; Endocrine Disruptors ; toxicity ; Estrogens ; toxicity ; Models, Theoretical ; Phenols ; toxicity ; Rats ; Rats, Sprague-Dawley ; Risk Assessment

Bisphenol A (BPA) is a commonly used phenolic environmental estrogen. Long-term exposure of female mammalians to BPA can lead to endocrine disorders, followed by the morphological and functional changes in ovary, uterus, vagina, and oviducts. The interactions of BPA with various target molecules or tissues will cause different effects. To further elucidate the effects of BPA on female reproductive system, we review the changes in the structure and functions of female reproduction system after BPA exposure and their possible mechanisms.
Benzhydryl Compounds ; toxicity ; Endocrine Disruptors ; toxicity ; Estrogens, Non-Steroidal ; toxicity ; Female ; Humans ; Ovary ; drug effects ; Phenols ; toxicity ; Uterus ; drug effects ; Vagina ; drug effects

Animals ; Endocrine Disruptors ; toxicity ; Lethal Dose 50 ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Thyrotropin ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo verify the antagonistic effect of Bushen Tianjing Recipe (BTR) on environmental endocrine disruptors (EEDs) induced gonadal dysgenesis (GD) Sprague-Dawley (SD) male rat model.

METHODSTotally 70 3-week-old male SD rats were randomly divided into seven groups, i.e., the control group (fed with corn oil), the model A group [di-2-ethylhexyl-phthalate (DEHP) 500 mg/kg], the CM A group (fed with DEHP 500 mg/kg + BTR 40 mL/kg), the exposed group B (fed with CYP 80 mg/kg), the CM B group (fed with CYP 80 mg/kg + BTR 40 mL/kg), the model C group [fed with DEHP 500 mg/kg + CYP 80 mL/kg], the CM C group (DEHP 500 mg/kg + CYP 80 mg/kg + BTR 40 mL/kg), respectively, 10 in each group. All were administered with corresponding medication by gastrogavage, once daily, for total 30 days. Rats were killed 24 h after the last administration, and their body weight and wet testis weight were weighed. The coefficient of testis was calculated. The serum testosterone (T) level was measured by chemiluminescent immunoassay. The histopathologic tissue was prepared. The ultrastructural changes of genital cells were observed by electron microscope.

RESULTSCompared with the control group, there was no statistical difference in the body weight increase among all groups (P > 0.05). The time of testicular descent and preputial separation were significantly delayed in each exposed group (P < 0.01). In the exposed group A and the exposed group C, the wet weight of the testes was reduced and serum T level decreased (P < 0.01). The coefficient of testis significantly decreased in the exposed group A (P < 0.01). Compared with corresponding model group, the time of testicular descent and preputial separation were significantly fore-laid in each corresponding CM group (P < 0.01). The weight of the testes, the coefficient of testis, and the serum T level increased in the CM A group (P < 0.01). The serum T level obviously increased in the CM B group (P < 0.05).

CONCLUSIONSThe GD rat model was successfully duplicated by using DEHP. EEDs were proved to have significant anti-androgen activities. BTR was verified to have significant antagonistic to its anti-androgen effect.

Animals ; Diethylhexyl Phthalate ; toxicity ; Drugs, Chinese Herbal ; therapeutic use ; Endocrine Disruptors ; toxicity ; Gonadal Dysgenesis ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

Ochratoxin A (OTA) is found not only nephrotoxic, teratogenic, neurotoxic, and immunotoxic, but also reprotoxic for human and animals. In the recent decade, more attention has been paid to the impact of OTA on human reproduction and the studies of its underlying mechanisms. Many studies show that OTA affects the function of the reproductive system by acting as an endocrine disrupter and, as a testicular toxin, decreases sperm quality and even induces testis cancer. This review summarizes the toxicological characteristics and toxicokinetic process of OTA as well as recent progress in the studies of various toxic effects of OTA and their underlying mechanisms, hoping to call the attention from more people to the toxicity of OTA to male reproductive health.
Animals ; Endocrine Disruptors ; pharmacokinetics ; toxicity ; Fertility ; drug effects ; Humans ; Male ; Ochratoxins ; pharmacokinetics ; toxicity ; Reproduction ; drug effects ; Spermatozoa ; drug effects ; Testicular Neoplasms ; chemically induced ; Testis ; drug effects

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.
Animals ; Biomarkers ; Endocrine Disruptors/toxicity* ; Environmental Exposure/adverse effects* ; Environmental Pollutants/toxicity* ; Hypothalamo-Hypophyseal System/physiopathology* ; Infertility, Male/physiopathology* ; Male ; Phenols/toxicity* ; Rats ; Rats, Sprague-Dawley ; Sulfones/toxicity* ; Testis/physiopathology* ; Toxicity Tests, Chronic

OBJECTIVETo observe the effects of fenvalerate on calcium homeostasis in rat ovary.

METHODSFemale Sprague-Dawley rats were orally given fenvalerate at daily doses of 0.00, 1.91, 9.55, and 31.80 mg/kg for four weeks. The ovary ultrastucture was observed by electron microscopy. Serum free calcium concentration was measured by atomic absorption spectrophotometry. The activities of phosphorylase a in rat ovary were evaluated by the chromatometry. The total content of calmodulin in ovary was estimated by ELISA at each stage of estrous cycle. Radioimmunoassay (RIA) was used to evaluate the level of serum progesterone.

RESULTSHistopathologically, damages of ovarian corpus luteum cells were observed. An increase in serum free calcium concentration was observed in rats treated with 31.80 mg/kg fenvalerate. The activities of phosphorylase a enhanced in all treated groups, and fenvalerate increased the total content of calmodulin significantly in estrus period. Serum progesterone levels declined in fenvalerate exposed rats in diestrus.

CONCLUSIONFenvalerate interferes with calcium homeostasis in rat ovary. Also, the inhibitory effects of fenvalerate on serum progesterone levels may be mediated partly through calcium signals.

Animals ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Calmodulin ; metabolism ; Endocrine Disruptors ; toxicity ; Female ; Homeostasis ; drug effects ; Insecticides ; toxicity ; Nitriles ; toxicity ; Ovary ; drug effects ; metabolism ; pathology ; Progesterone ; blood ; Pyrethrins ; toxicity ; Rats ; Rats, Sprague-Dawley