The Joint Effect of Perceived Psychosocial Stress and Phthalate Exposure on Hormonal Concentrations during the Early Stage of Pregnancy: A Cross-Sectional Study.

Phthalates alter the hormonal balance in humans during pregnancy, potentially affecting embryonic and fetal development. We studied the joint effect of exposure to phthalates, quantified by urinary phthalate metabolite concentration, and perceived psychological stress on the concentration of hormones in pregnant women (n = 90) from the Nitra region, Slovakia, up to the 15th week of pregnancy. We used high-performance liquid chromatography, tandem mass spectrometry (HPLC-MS/MS), and electro-chemiluminescence immunoassay to determine urinary concentrations of phthalates and serum concentrations of hormones, respectively. We used Cohen perceived stress scale (PSS) to evaluate the human perception of stressful situations. Our results showed that mono(carboxy-methyl-heptyl) phthalate (cx-MiNP) and a molar sum of di-iso-nonyl phthalate metabolites (ΣDiNP) were negatively associated with luteinizing hormone (LH) (p ≤ 0.05). Mono(hydroxy-methyl-octyl) phthalate (OH-MiNP) and the molar sum of high-molecular-weight phthalate metabolites (ΣHMWP) were positively associated with estradiol (p ≤ 0.05). PSS score was not significantly associated with hormonal concentrations. When the interaction effects of PSS score and monoethyl phthalate (MEP), cx-MiNP, ΣDiNP, and ΣHMWP on LH were analyzed, the associations were positive (p ≤ 0.05). Our cross-sectional study highlights that joint psychosocial stress and xenobiotic-induced stress caused by phthalates are associated with modulated concentrations of reproductive hormones in pregnant women.

Effects and Mechanisms of Phthalates' Action on Reproductive Processes and Reproductive Health: A Literature Review.

The production of plastic products, which requires phthalate plasticizers, has resulted in the problems for human health, especially that of reproductive health. Phthalate exposure can induce reproductive disorders at various regulatory levels. The aim of this review was to compile the evidence concerning the association between phthalates and reproductive diseases, phthalates-induced reproductive disorders, and their possible endocrine and intracellular mechanisms. Phthalates may induce alterations in puberty, the development of testicular dysgenesis syndrome, cancer, and fertility disorders in both males and females. At the hormonal level, phthalates can modify the release of hypothalamic, pituitary, and peripheral hormones. At the intracellular level, phthalates can interfere with nuclear receptors, membrane receptors, intracellular signaling pathways, and modulate gene expression associated with reproduction. To understand and to treat the adverse effects of phthalates on human health, it is essential to expand the current knowledge concerning their mechanism of action in the organism.

Exposure of children to phthalates and the impact of consumer practices in Slovakia.

Phthalates are environmental pollutants that can enter the human body by ingestion, inhalation and dermal absorption. Food constitutes the most important source of human exposure to these chemicals. The aim of our study was the biological monitoring of exposure to eight phthalate metabolites in children (n=107), 10-12 years of age, living in eastern Slovakia. Additionally, we analysed some associations between anthropometric measures, questionnaire data (i.e. eating and drinking habits, practice of personal care products) and concentrations of phthalate metabolites. Because of the short half-life of phthalates, within 24-48 h, we used 24-h recalls to assess dietary intakes. We used high-performance liquid chromatography and tandem mass spectrometry for the analysis of spot urine samples to determine concentrations of phthalate metabolites mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-benzyl phthalate (MBzP), mono (2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-carboxy pentyl and mono (2-ethylhexyl) phthalate (MEHP). We found statistically significant association between consumer practices and concentration of some phthalate metabolites, concretely consumption of milk and dairy products with MBzP and margarine with MEP (p<0.01 in both cases) and margarine with 5oxo-MEHP, hot beverages with 5OH-MEHP, baguettes and semifinished products with MEP (p<0.05 in all cases). Further, we found relationship between use of cosmetic products and phthalate concentrations, nail polish application and MEP and use of body lotion and MEHP (p<0.05 in both cases). We concluded that consumer practices (including eating and drinking habits and personal care) represent the substantial source of phthalate exposure in Slovak children.

Occupational exposure to phthalates in relation to gender, consumer practices and body composition.

The aim of our work was to find associations between urinary phthalate metabolite concentrations and occupation, consumer practices and body composition. We divided our cohort (n = 129) into occupationally exposed subjects, community service workers (group A; n = 45) and workers from plastic industry (group B; n = 35) and group of general population (control group C, n = 49). To estimate levels of five phthalate metabolites, we used high-performance liquid chromatography and tandem mass spectrometry analysis. We found in plastic industry workers compared to community service workers and subjects of the control group significantly higher urinary concentration mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-etylhexyl) phthalate (MEHP), sum di-(2-ethyl-5-oxohexyl) phthalate (DEHP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP). We identified by multivariate analysis of covariance inverse relationship between MEHP and body parameters as waist-to-height ratio, body mass index, waist-to-hip ratio, hip circumference and waist circumference among females, whereas in males, no significant association was found. Results of our study show, despite of variability in terms of occupational exposure to phthalates, that plastic manufactory represents a higher occupational risk in comparison with waste management. The differences in anthropometric parameters between the two occupationally exposed groups and the general population are suggesting a detrimental effect of occupational exposure on body weight homeostasis.

Relationship between variation of seasonal temperature and extent of occupational exposure to phthalates.

Spot urine samples were collected in summer and winter season to examine the association between temperature variation and phthalate concentration in an occupationally exposed group. We analysed samples by high-performance liquid chromatography with mass spectrometry (HPLC-MS/MS) to determine the concentrations of four phthalate metabolites: mono (2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MnBP), monoethyl phthalate (MEP), and monoisononyl phthalate (MiNP). We observed significantly higher urinary concentrations of all monitored phthalate metabolites collected during the summer in occupationally exposed group (MEP p < 0.0015, MiNP p < 0.0001, MnBP p < 0.00019, and MEHP p < 0.05); however, in general, population was noticed this difference only for MEHP (p < 0.05) in winter season. We conclude that increasing indoor and outdoor temperature is related to phthalate exposure in specific types of work environment.

Phthalate exposure and health-related outcomes in specific types of work environment.

Many toxic substances in the workplace can modify human health and quality of life and there is still insufficient data on respiratory outcomes in adults exposed to phthalates. The aim of this work was to assess in waste management workers from the Nitra region of Slovakia (n = 30) the extent of exposure to phthalates and health-related outcomes. Four urinary phthalate metabolites mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MnBP), monoethyl phthalate (MEP) and monoisononyl phthalate (MiNP) were determined by high-performance liquid chromatography with mass spectrometry (HPLC-MS/MS). Urinary concentration of MEHP was positively associated with ratio of forced expiratory volume in 1 s to forced vital capacity % (FEV1/FVC) (r = 0.431; p = 0.018) and MiNP with fat free mass index (FFMI) (r = 0.439; p = 0.015). The strongest predictor of pulmonary function was the pack/year index as smoking history that predicted a decrease of pulmonary parameters, the FEV1/FVC, % of predicted values of peak expiratory flow (PEF % of PV) and FEV1 % of PV. Unexpectedly, urinary MEHP and MINP were positively associated with pulmonary function expressed as PEF % of PV and FEV1/FVC. We hypothesize that occupational exposure to phthalates estimated from urinary metabolites (MEHP, MiNP) can modify pulmonary function on top of lifestyle factors.

Nuclear and nucleolar reprogramming during the first cell cycle in bovine nuclear transfer embryos.

The immediate events of genomic reprogramming at somatic cell nuclear transfer (SCNT) are to high degree unknown. This study was designed to evaluate the nuclear and nucleolar changes during the first cell cycle. Bovine SCNT embryos were produced from starved bovine fibroblasts and fixed at 0.5, 1, 2, 3, 4, 8, 12, and 16 h postactivation (hpa). Parthenogenetic (PA) embryos were used as control. The SCNT and PA embryos were processed for lacmoid staining, autoradiography, transmission electron microscopy (TEM), and immunofluorescence localization of: upstream binding factor (UBF) and fibrillarin at 4 and 12 hpa. Likewise, starved and nonstarved fibroblasts were processed for autoradiography and TEM. The fibroblasts displayed strong transcriptional activity and active fibrillogranular nucleoli. None of the reconstructed embryos, however, displayed transcriptional activity. In conclusion, somatic cell nuclei introduced into enucleated oocytes displayed chromatin condensation, partial nuclear envelope breakdown, nucleolar desegregation and transcriptional quiescence already at 0.5 hpa. Somatic cell cytoplasm remained temporally attached to introduced nucleus and nucleolus was partially restored indicating somatic influence in the early SCNT phases. At 1-3 hpa, chromatin gradually decondensed toward the nucleus periphery and nuclear envelope reformed. From 4 hpa, the somatic cell nucleus gained a PN-like appearance and displayed NPBs suggesting ooplasmic control of development.