Effects of prenatal and lactational bisphenol a and/or di(2-ethylhexyl) phthalate exposure on male reproductive system.

Bisphenol A (BPA) and phthalates are abundantly used endocrine disrupting chemicals (EDCs). The aim of this study was to evaluate the effects of single and combined exposures to BPA and/or di(2-ethylhexyl) phthalate (DEHP) in prenatal and lactational period on rat male reproductive system in later stages of life. Pregnant Sprague-Dawley rats were divided randomly to four groups (n = 3/group): Control (corn oil); DEHP (30 mg/kg/day); BPA (50 mg/kg/day); and BPA+ DEHP (30 mg/kg/day DEHP and 50 mg/kg/day BPA). Groups exposed to EDCs through 6-21 gestational days and lactation period by intragastric lavage. Male offspring (n = 6/group) from each mother were fed till adulthood and were then euthanized. Later, reproductive hormones, sperm parameters, and oxidative stress parameters were determined. In conclusion, we can suggest that prenatal and lactational exposure to BPA and DEHP may cause adverse effects in male reproductive system in later stages of life especially after combined exposure.

Bisphenol A and phthalate levels in adolescents with polycystic ovary syndrome.

Endocrine disruptors have been proposed in the etiology of polycystic ovary syndrome (PCOS) as they have the potency to interfere with hormone-sensitivity systems. The aim of this study was to evaluate the levels of bisphenol A (BPA) and phtalates in adolescents with PCOS. Sixty-two girls with PCOS and 33 controls, age 12-18 years were enrolled in the study. The diagnosis of PCOS was made using modified Rotterdam criteria. Urinary BPA levels were measured using high-performance liquid chromatography. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used phthalate and mono-(2-ethylhexyl)-phthalate (MEHP), its main metabolite were measured by using high-performance liquid chromatography. Adolescents with PCOS had markedly increased BPA levels (15.89 µg/g creatine ± 1.16) when compared with the control group (7.30 µg/g creatine ± 1.38) (p = .016). In adolescents with PCOS, BPA was significantly correlated with polycystic morphology on ultrasound but not with obesity androgen levels, or other metabolic parameters. Patients with PCOS (DEHP: 0.40 ppm ± 0.24, MEHP: 0.13 ppm ± 0.23) and controls (DEHP: 0.49 ppm ± 0.27, MEHP: 0.14 ppm ± 0.3) had similar serum phtalate concentrations (p = .7 and p = .3, respectively). Exposure to specific endocrine disruptors such as BPA could modify neuroendocrine, reproductive, and metabolic regulation favoring PCOS development in adolescents.

The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty.

Exposure to environmental chemicals can affect genetic and epigenetic molecular pathways and may cause altered growth and development. Among those exposures, endocrine-disrupting chemicals (EDCs) are of particular concern as humans are abundantly exposed to these chemicals by various means in every period of life. Several well-known environmental chemicals, including phthalates and bisphenol A (BPA), are classified as EDCs. These EDCs are suggested to play roles in early onset of puberty in girls. The aim of this study is to determine plasma phthalate (di(2-ethylhexyl)phthalate [DEHP] and its main metabolite mono(2-ethylhexyl)phthalate [MEHP]) and urinary BPA levels in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). This study was performed on newly diagnosed idiopathic central precocious puberty (CPP) patients (n = 42) and peripheral precocious puberty (PPP) (n = 42) patients, who were admitted to Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology between August 2012 and -July 2013. Nonobese healthy girls (n = 50) were used as the control group. Urinary BPA levels were not statistically different in control, PPP and CPP groups (medians 10.91, 10.63 and 10.15 µg/g creatinine, respectively; p > 0.05). Plasma DEHP levels were significantly higher in PPP group when compared to control. Plasma MEHP levels were not significantly different in control and PPP groups (p > 0.05). However, in CPP group, both plasma DEHP and MEHP levels were significantly higher than control and PPP groups. This study showed that phthalates might play a role in the occurence of CPP in girls.

Associations between pediatric intensive care procedures and urinary free-BPA levels.

BACKGROUND: Bisphenol A (BPA) is found in many medical materials used in the paediatric intensive care unit (PICU). Our aim was to evaluate how the urinary free-BPA(fBPA) and total-BPA(tBPA) levels were associated with the use of medical devices in the PICU in a prospective study. METHODS: The procedures applied to the patient were recorded during the follow-up period. Three urine samples were taken on the first day of hospitalization; the seventh day, and after 30 days or when the patients were discharged. Urinary tBPA and fBPA levels were determined using high-pressure liquid chromatography. Generalized estimating equations with repetitive measures were used to determine the associations between PICU procedures and BPA levels. RESULTS: A total of 115 urine samples of 40 children were studied. Mean urinary levels were 189.2 µg/g-creatinine for tBPA and 27.8 µg/g-creatinine for fBPA, and the fBPA/tBPA ratio was 27.9%. Endotracheal intubation, catheter, and haemodialysis procedures caused higher urinary fBPA levels. External drains, inhaler treatment, and the use of four or more medical devices were associated with considerably higher values of fBPA%. The increase in tBPA was positively correlated with fBPA. CONCLUSIONS: fBPA levels and the fBPA/tBPA ratio varied according to the procedure and level of BPA exposure in children.

Toxic Effects of Tetrabromobisphenol A: Focus on Endocrine Disruption.

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is used in a variety of consumer products such as electronic equipment, fire extinguishers, furniture, plastics, textiles, and kitchen hoods. Most studies show that the TBBPA production process and TBBPA in industrial and urban sewage waste result in extensive human exposure and environmental contamination. TBBPA can accumulate in organisms, particularly aquatic life, and is classified as a group 2A carcinogen (likely carcinogenic to humans) by the International Agency for Research on Cancer. This compound produces low acute toxicity, but chronic exposure may produce serious consequences. In this review, we focus on TBBPA toxicity by discussing results of various studies that were published in the last two decades. Studies show that TBBPA acts as an endocrine disruptor, causing neurobehavioral and immunotoxic effects, oxidative stress, and apoptosis. Although several experiments were performed in vitro and in vivo, human data are lacking, and thus, chronic toxic effects of TBBPA on humans are not well known, particularly in sensitive populations including pregnant women, newborns, children, and the elderly. Epidemiological studies that comprehensively assess TBBPA levels in biological fluids of different populations and in different pathological conditions are needed. Research on the impact of TBBPA, particularly regarding endocrine disorders and cancer, must also be performed.

The association between urinary BPA levels and medical equipment among pediatric intensive care patients.

We aim to evaluate urinary total BPA (tBPA) levels and association with medical devices used on patients in pediatric intensive care units. This cross-sectional descriptive study included 117 critically ill children. Urinary tBPA levels were determined using high-performance liquid chromatography. General estimating equations with repeated measures analyzed the effect of interventions and devices on urinary BPA levels. A total of 292 urine samples taken from 117 child intensive care patients were studied. When age, sex, and body mass index-for age z-scores were controlled, cases having endotracheal intubation showed higher urinary tBPA levels (p = 0.003) and hemodialyzed patients had considerably higher urinary tBPA levels (p = 0.004). When confounding factors were controlled, cases using both multiple iv treatment and more than four medical devices showed higher urinary tBPA levels than their counterparts (p = 0.007 and p = 0.028, respectively). The use of certain medical devices and interventions could increase BPA exposure in pediatric intensive care patients.

Neuroendocrine disruption by bisphenol A and/or di(2-ethylhexyl) phthalate after prenatal, early postnatal and lactational exposure.

Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP) are abundant endocrine disrupting chemicals (EDCs). In recent years, studies showed that EDCs may lead to neurodevelopmental diseases. The effects of prenatal exposure to these chemicals may have serious consequences. Moreover, exposure to EDCs as a mixture may have different effects than individual exposures. The present study aimed to determine the toxicity of BPA and/or DEHP on central nervous system (CNS) and neuroendocrine system in prenatal and lactational period in Sprague-Dawley rats. Pregnant rats were randomly divided into four groups: control (received vehicle); BPA group (received BPA at 50 mg/kg/day); DEHP group (received DEHP at 30 mg/kg/day); and combined exposure group (received both BPA at 50 mg/kg/day and DEHP at 30 mg/kg/day) during pregnancy and lactation by oral gavage. At the end of lactation, male offspring (n = 6) were randomly grouped. The alterations in the brain histopathology, neurotransmitter levels and enzyme activities in the cerebrum region, oxidative stress markers, and apoptotic effects in the hippocampus region were determined at adulthood. The results showed that exposure to EDCs at early stages of life caused significant changes in lipid peroxidation, total GSH and neurotransmitter levels, and activities of neurotransmitter-related enzymes. Moreover, BPA and/or DEHP led to apoptosis and histopathologic alterations in the hippocampus. Therefore, we can suggest that changes in oxidant/antioxidant status, as well as in neurotransmitters and related enzymes, can be considered as the underlying neurotoxicity mechanisms of BPA and DEHP. However, more mechanistic studies are needed.

Histopathologic, apoptotic and autophagic, effects of prenatal bisphenol A and/or di(2-ethylhexyl) phthalate exposure on prepubertal rat testis.

Bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP) are endocrine-disrupting chemicals (EDCs) used in a wide variety of industrial products as plasticizers. Exposure to EDCs, particularly in mixtures, in prenatal and early postnatal periods may lead to unwanted effects and can cause both developmental and reproductive problems. In this study, we aimed to determine the individual and combined effects of prenatal and lactational exposure to BPA and/or DEHP on testicular histology, apoptosis, and autophagic proteins. Pregnant Sprague-Dawley rats (n = 3) were divided into four groups (control, BPA (50 mg/kg/day), DEHP (30 mg/kg/day), and BPA (50 mg/kg/day) + DEHP (30 mg/kg/day)) and dosed by oral gavage during pregnancy and lactation. The male offspring (n = 6) from each group were chosen randomly, and their testicular examinations were performed on the twelfth week. The results showed that fetal and neonatal exposure to BPA and DEHP could lead to significant testicular histopathological alterations and cause increases in apoptosis markers (as evidenced by increases in caspase 3 and caspase 8 levels; increased TUNEL-positive spermatogonia and TUNEL-positive testicular apoptotic cells) and autophagic proteins (as evidenced by increased LC3 and Beclin levels and decreased p62 levels) in testicular tissue. We can suggest that EDCs cause more dramatic changes in both testicular structure and cell death when there is combined exposure.

Renal changes and apoptosis caused by subacute exposure to Aroclor 1254 in selenium-deficient and selenium-supplemented rats.

Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A - 34.92 % and ASeD - 86.46 %) and rise in LP (A - 30.45 % and ASeD - 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.

Prenatal bisphenol a and phthalate exposure are risk factors for male reproductive system development and cord blood sex hormone levels.

Bisphenol A (BPA) and phthalates can adversely affect the fetal development. However, observational studies on the effects of these chemicals on fetal male reproductive system are still limited. A hundred of umbilical cord blood samples were analyzed for the levels of BPA, di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and sex hormones. After birth, male newborns underwent physical examination that included measurements of anogenital distance, stretched penile length (SPL), and penile width. BPA, DEHP and MEHP levels were detectable in ≈99% of cord blood samples. In covariate-adjusted models, cord blood BPA levels were inversely associated with SPL of newborns and positively associated with cord blood estradiol levels. In addition, there was a significant inverse relationship between cord blood DEHP levels and anogenital distance index of newborn males. Our results suggest that in utero BPA and DEHP exposure exerted adverse effects on fetal male reproductive development and cord blood estradiol levels.

Oxidative Stress Parameters, Selenium Levels, DNA Damage, and Phthalate Levels in Plastic Workers.

Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.

Urinary bisphenol-A levels in children with type 1 diabetes mellitus.

BACKGROUND: Bisphenol-A (BPA) is one of the most abundantly produced chemicals globally. Concerns have been raised about BPA's possible role in the pathogenesis of type 1 diabetes mellitus (T1DM). The main aim of the current study was to evaluate the possible association between BPA exposure and T1DM. The second aim was to investigate children's possible BPA exposure routes in Turkey. METHODS: A total of 100 children aged between 5 and 18 years including 50 children with T1DM and 50 healthy children were included. Urinary BPA levels of all children were measured using high-performance liquid chromatography. Mothers of children enrolled in the study were also requested to complete a survey that included questions on the sociodemographic characteristics, medical history and possible BPA exposure routes of their children. RESULTS: In the T1DM group, urinary BPA levels were slightly higher compared to the control group, but this difference was not significant (p=0.510). However, there was an inverse relationship between current urinary BPA levels and birth weight. It was found that the use of plastic kettles and the consumption of dairy products in plastic boxes significantly increased the urinary BPA concentrations in all subjects. CONCLUSIONS: Although there was no significant association between urinary BPA levels and T1DM, we found an inverse relationship between current urinary BPA levels and birth weight. This finding might be important for prenatal exposure, and further prospective research must be conducted. Also, the use of plastic kettles, which has not been mentioned much in the literature before, was found to be an important exposure route for BPA.

Copper, zinc and iron levels in premature infants following red blood cell transfusion.

This study aimed to investigate effect of erythrocyte suspension (ES) transfusion on Cu, Zn, and Fe levels. It was conducted on 53 premature infants who were admitted to Hacettepe Hospital and received EST for first time. Blood samples were drawn before and 96h after ES transfusion to determine Cu, Zn, and Fe levels in plasma and/or erythrocytes. The mean plasma Cu levels were 99±3µg/dl and 113±3µg/dl; Zn levels were 105±2µg/dl and 115±23µg/dl; mean plasma Fe level was 58.1±19.4 and 75.2±25.4µg/dl and mean erythrocyte Fe level was 4182±2314µg/ml and 7009±5228µg/ml, before and after ES transfusion. The differences between before and after ES transfusion in Cu, Zn and Fe levels were significant. Correlation between plasma and erythrocyte Fe levels was significant both before and after ES transfusion. Though Fe overload is a major cause of morbidity/mortality after ES transfusion, alterations in trace elements should also be considered when transfusing blood to infants and children.