Lactational exposure to polychlorinated biphenyls is higher in overweight /obese women and associated with altered infant growth trajectory: A pilot study.

BACKGROUND: Infant exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may contribute to developmental programming of long-term metabolic disease risk. PCBs persist given their lipophilicity and long half-lives, allowing them to bio-accumulate in adipose tissue. These compounds can then be excreted into maternal milk resulting in infant exposure. OBJECTIVE: To determine the level of PCBs in milk from mothers with pre-pregnancy overweight and obese (OW/OB) versus normal weight status (NW) and evaluate the association of milk PCB levels with infant growth over the first 6 months of life. METHODS: A pilot study of a subset of milk samples from mothers with NW (pre-pregnancy body mass index (BMI) < 25 kg/m2, n = 11) and OW/OB (pre-pregnancy BMI ≥ 25 kg/m2, n = 8) were examined approximately 2-weeks postpartum. PCB congeners 138 + 163, 132 + 153, 180, and the sum were measured using gas chromatography/mass spectrometry and adjusted for milk fat content. Infant growth was monitored from birth to 6 months for weight-for-age (WFA), length-for-age (LFA), weight-for-length (WFL), head circumference-for-age (HCA), and associations with milk PCB content determined using linear mixed modeling. RESULTS: Total milk fat content did not differ by maternal weight status (p = 0.88). Milk from mothers with OW/OB had significantly higher PCB sum (p = 0.02) and PCB 138 + 163 (p = 0.03). PCB 132 + 153 (ß -0.0008, p = 0.0218), PCB 180 (ß -0.0010, p = 0.0279), and PCB sum (ß -0.0006, p = 0.0138) were negatively associated with HCA Z-score growth to 6 months. PCB 180 was negatively associated with infant WFA (ß -0.0015, p = 0.0058) and WFL Z-score (ß -0.0016, p = 0.0263) to 6 months. There were no associations of PCB sum content with WFL, LFA, WFL Z-score over the first 6 months of life. CONCLUSIONS: Maternal overweight and obesity are associated with higher levels of total PCB congeners (132, 138, 153, 163, 180) in human milk. PCB congeners have negative associations with infant head circumference and weight trajectory over the first 6 months of life.

Phthalate metabolites concentrations in amniotic fluid and maternal urine: Cumulative exposure and risk assessment.

Phthalates are used in industry as plasticizers or additives in everyday products and they have been considered as endocrine disrupting chemicals. Maternal exposure during pregnancy has been associated with neonatal exposure, preterm birth and impacts in the reproductive and respiratory systems. The aim of this study is to determine six phthalate metabolites (mono isobutyl phthalate, miBP, mono n-butyl phthalate, mnBP, mono benzyl phthalate, mBzP, mono ethylhexyl phthalate, mEHP, mono 2-ethyl-5-hydroxyhexyl phthalate, mEHHP, mono 2-ethyl-5-oxohexyl-phthalate, mEOHP) in amniotic fluid and urine from 100 pregnant women. Participants answered questionnaires for the use of plastics and cosmetics, dietary habits, health effects, pregnancy problems, health and infant development. Positive amniotic fluid samples ranged from 1% to 21% and urine from 27% to 54%. The median levels for amniotic fluid were 2.3 µg/L - 10.7 µg/L and for urine 4.9 µg/L - 46.7 µg/L. The major results include significant correlations between urinary phthalates indicating their common sources of exposure, the frequent use of deodorant was significantly associated with higher urinary miBP (p = 0.050) and mnBP (p = 0.028) and a weak inverse association was found for the use of make-up products with mBzP (p = 0.053). The frequent use of plastic food containers was significantly associated with urinary mEHP (p = 0.026), and a positive trend was noticed for mEHP in amniotic fluid (p = 0.093). An association although weak was found between urinary mEHP and lower birth length (rs = 0.396, p = 0.062). No other associations were found for infant health problems or development. The daily intake of the total phthalates was calculated 5.4 µg/kg body weight/day which corresponds to hazard index 0.10 and exposure follows the declining trend that has been observed the last decades.

Acrylamide induces a thyroid allostasis-adaptive response in prepubertal exposed rats.

Some endocrine-disrupting chemicals (EDCs) can affect the endocrine system through covalent interactions with specific sites, leading to deregulation of physiological homeostasis. The acrylamide (AA) present in some fried or baked foods is an example of an electrophile molecule that is able to form adducts with nucleophilic regions of nervous system proteins leading to neurological defects. A positive correlation between increased urinary AA metabolite concentration and reduced levels of thyroid hormones (TH) was described in adolescents and young adults. Thus, this study aimed to evaluate whether AA affects the physiology of the hypothalamus-pituitary-thyroid (HPT) axis and the possible repercussions in peripheral TH-target systems. For this, male Wistar rats were exposed to doses of 2.5 or 5.0 mg AA/Kg/day, based on the LOAEL (Lowest Observed Adverse Effect Level) during prepubertal development. The expression of molecular markers of HPT functionality was investigated in the hypothalamus, pituitary, thyroid, heart and liver, as well as the hormonal and lipid profiles in blood samples. Herein, we showed that AA acts as EDCs for thyroid gland function, increasing the transcript expression of several proteins related to TH synthesis and altering hypothalamus-pituitary-thyroid axis homeostasis, an effect evidenced by the higher levels of THs in the serum. Compensatory mechanisms were observed in TH-target tissues, such as an increase in Dio3 mRNA expression in the liver and a reduction in Mct8 transcript content in the hearts of AA-treated rats. Together, these results pointed out an allostatic regulation of the HPT axis induced by AA and suggest that chronic exposure to it, mainly associated with food consumption, might be related to the higher prevalence of thyroid dysfunctions.

Cell junctions in the prostate: an overview about the effects of Endocrine Disrupting Chemicals (EDCS) in different experimental models.

Throughout the last decades, increasing exposure to environmental Endocrine Disruptors Chemicals (EDCs) has been associated with the occurrence of male reproductive disorders, such as impairment of prostate development and function, increase of susceptibility to oncogenesis, Epithelial-Mesenchymal Transition and the metastatic invasive potential. Nevertheless, few studies address the mechanisms involved in these alterations, especially those related to cell junctions, which are hormonally regulated and, therefore, possible EDCs targets. The cellular mechanisms discussed in this review are addressed to EDCs actions on tight, gap and adherent junctions and its related genes and proteins, such as claudin-1, -3, -4 and -8, connexin-32 and -43, E-cadherin and ß-catenin, respectively. The impairment of cell junction function, mainly due EDCs exposure during the prostate's critical window of development, can corroborate to acquire a mesenchymal phenotype by epithelial cells and the prostate microenvironment becomes susceptible to development of lesions in the latter stages of life.

Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD.

People are frequently and unintentionally exposed to many chemical compounds, such as environmental pollutants and endocrine-disrupting chemicals (EDCs), in food and from the atmosphere. In particular, endocrine-disrupting TBBPA and dioxins are found in human breast milk and in the body. Conventional studies evaluate toxicity by administering a single substance to cells or animals, but evaluation of the toxicity of mixtures of these ingested compounds is essential for "true" toxicological assessment. We evaluated toxic effects in vitro using human mesenchymal stem cells (hMSCs). TBBPA increased the number of lipid droplets, and upregulated the expression of adipocyte-related mRNA, aP2 and LPL, through a PPARγ-dependent mechanism. TCDD suppressed lipid droplets and adipocyte-related mRNA levels. Adipocyte differentiation was stimulated by TBBPA and inhibited by TCDD in a dose-dependent manner. TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances.

Conazole fungicides inhibit Leydig cell testosterone secretion and androgen receptor activation in vitro.

Conazole fungicides are widely used in agriculture despite their suspected endocrine disrupting properties. In this study, the potential (anti-)androgenic effects of ten conazoles were assessed and mutually compared with existing data. Effects of cyproconazole (CYPRO), fluconazole (FLUC), flusilazole (FLUS), hexaconazole (HEXA), myconazole (MYC), penconazole (PEN), prochloraz (PRO), tebuconazole (TEBU), triadimefon (TRIA), and triticonazole (TRIT) were examined using murine Leydig (MA-10) cells and human T47D-ARE cells stably transfected with an androgen responsive element and a firefly luciferase reporter gene. Six conazoles caused a decrease in basal testosterone (T) secretion by MA-10 cells varying from 61% up to 12% compared to vehicle-treated control. T secretion was concentration-dependently inhibited after exposure of MA-10 cells to several concentrations of FLUS (IC50 = 12.4 µM) or TEBU (IC50 = 2.4 µM) in combination with LH. The expression of steroidogenic and cholesterol biosynthesis genes was not changed by conazole exposure. Also, there were no changes in reactive oxygen species (ROS) formation that could explain the altered T secretion after exposure to conazoles. Nine conazoles decreased T-induced AR activation (IC50s ranging from 10.7 to 71.5 µM) and effect potencies (REPs) were calculated relative to the known AR antagonist flutamide (FLUT). FLUC had no effect on AR activation by T. FLUS was the most potent (REP = 3.61) and MYC the least potent (REP = 0.03) AR antagonist. All other conazoles had a comparable REP from 0.12 to 0.38. Our results show distinct in vitro anti-androgenic effects of several conazole fungicides arising from two mechanisms: inhibition of T secretion and AR antagonism, suggesting potential testicular toxic effects. These effects warrant further mechanistic investigation and clearly show the need for accurate exposure data in order to perform proper (human) risk assessment of this class of compounds.