Bisphenol A (BPA) exposure during the perinatal and postnatal periods increases the susceptibility to disease over the life cycle. However, information on the BPA delivered to fetuses or infants via ...the placenta and breastfeeding is limited. We determined the BPA exposure levels in various bodily fluids and tissues of pregnant women and described fetus and infant exposures to BPA based on associations and BPA ratios in mother–neonate paired samples. Maternal serum, urine, placenta, breast milk, cord serum, and neonatal urine samples were collected from 318 mother–neonate pairs at six university hospitals in Korea. BPA levels were detected using liquid chromatography tandem mass spectrometry. The ratios of the BPA levels in the other sample types to the levels in maternal serum were calculated. BPA was detected in 79.5–100% of the maternal and fetal samples. The median BPA concentration in the samples decreased in the order of neonatal urine (4.75ng/mL), maternal urine (2.86ng/mL), cord serum (1.71ng/mL), maternal serum (1.56ng/mL), breast milk (0.74ng/mL), and the placenta (0.53ng/g). We estimated the ratios of BPA levels in the other sample types to those in maternal serum. The median (95th percentile) cord serum-to-maternal serum ratio was 1.12 (15.2) for 160 mother–fetal pairs, in which BPA was detected in both samples. The placenta-, maternal urine-, neonatal urine-, and breast milk-to-maternal serum ratios were 0.28 (5.31), 1.79 (29.9), 1.98 (28.2), and 0.51 (10.5), respectively. In addition, the median (95th percentile) cord serum-to-placenta ratio was 4.03 (45.8), and the neonatal urine-to-cord serum ratio was 1.95 (25.6). The 95th percentile values were 14–20-fold greater than the medians. Urine contained the highest BPA concentrations, followed by serum, breast milk, and the placenta. The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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•Not enough data on tissue distribution of BPA in mother‑neonate (or fetus) pair•The order of BPA concentrations in examined tissue or bio-samples are urine in mother and neonates>cord serum>maternal serum>breast milk>placenta.•BPA in cord serum, significantly associated with in maternal serum and urine but not in others.•The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•PFOS, PFOA, PFUnDA, and PFNA were the predominant compounds in breast milk.•Concentrations of PFASs were significantly correlated with maternal age, BMI, and parity.•Increased levels of PFASs were ...found in breast milk after the first month of nursing.•Snack consumption and frequency of eating-out were significantly associated with increased PFAS levels.•The infant exposure levels of PFOS and PFOA via breast milk were lower than the TDI.
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Breastfeeding is an important exposure pathway to perfluoroalkyl substances (PFASs) for newborn infants. Nevertheless, reports are limited on the occurrence and time-course of PFASs in breast milk, and most studies have focused on the analysis of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). In this study, 16 PFASs were analyzed in breast milk samples (n=293) collected from 128 mothers in Korea during various lactation periods to assess maternal exposure levels, contamination profiles, time-course variations, and infant health risks. The total concentrations of PFASs (ΣPFAS) ranged from 31.7 to 1004 (median: 188) ng/L, which was within the ranges recently reported for Asian and European populations. After a month of nursing, the concentrations of PFOS, PFOA, perfluorononanoic acid (PFNA), and ΣPFAS significantly increased. This could be due to changes in the dietary and behavior patterns of the mothers after the first month of lactation. The concentrations of PFOS and PFOA were significantly correlated with maternal age, body mass index, and parity. Certain types of diet (e.g. consuming snacks and milk) and eating-out frequency were significantly associated with increasing levels of PFAS. Significant correlations and similar time-course trends were found between PFASs and PCBs/DDTs, implying similar exposure sources and biokinetics for these contaminants. The estimated daily intakes of PFOS and PFOA via the consumption of breast milk were below the tolerable daily intakes for infants suggested by the European Food Safety Authority (EFSA).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha‐lipoic acid ...(ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA‐related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis, protein–protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein‐to‐protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top 10 hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple targets and multiple pathways mechanisms.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The placenta is a crucial organ for the supply of oxygen and nutritional elements from mother to fetus. Several studies have reported evidence of the placental transfer of persistent organic ...pollutants (POPs). Despite the importance of prenatal exposure to POPs, the transport process of POPs via the human placenta is not well understood. To investigate the transport processes of these contaminants and to assess the feasibility of the placenta as a non-invasive biological matrix, we measured 19 polychlorinated biphenyls (PCBs), 18 organochlorine pesticides (OCPs), and 24 polybrominated diphenyl ethers (PBDEs) in placenta tissues. The total concentrations of PCBs, OCPs, and PBDEs in placental tissues ranged from 0.36 to 75.2 (median: 5.85) ng/g lipid wt, 1.37 to 250 (63.5) ng/g lipid wt, and 1.21 to 427 (11.7) ng/g lipid wt, respectively. The BDE 209 concentrations were higher than those reported in previous studies presumably because of the high consumption of deca-BDE technical mixtures in Korea. The concentrations of all of the POPs in placental tissues correlated significantly with each other, but BDE 209 concentration did not correlate with that of any other contaminants possibly because of different exposure sources and kinetics. Maternal age, body mass index, and parity were contributors to the accumulation of several POPs in the placenta. Partitioning ratios between maternal blood–placenta–cord blood showed that lower molecular-weight and hydrophobic POPs were preferentially transported from maternal blood to the placenta and that higher molecular-weight and hydrophobic contaminants tended to remain in placental tissues. Regression analysis showed significant relationships between the POP concentrations in multiple biological matrices such as maternal blood, placenta, cord blood, and meconium. These relationships suggest that the placenta can be used as a non-invasive matrix for biomonitoring prenatal exposure to several POPs.
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•PCBs, OCPs, and PBDEs were measured in 108 placental tissues from the Korean women.•Maternal age, body mass index, and parity were related to placental POP levels.•Molecular weight and liposolubility influenced POP transport via the human placenta.•The placenta may be a non-invasive matrix for biomonitoring of prenatal POP exposure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Current knowledge on adverse endocrine disruption effects of persistent organic pollutants (POPs) among newborn infants is limited and often controversial. To investigate the associations between ...prenatal exposure to major POPs and thyroid hormone levels among newborn infants, both cord serum or maternal serum concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) were compared with five thyroid hormones in cord serum of newborn infants as well as TSH in bloodspot collected at 2 day after birth (n=104). Since cord serum thyroid hormones could be affected by those of mothers, thyroid hormone concentrations of the matching mothers at delivery were adjusted. In cord serum, BDE-47, -99, and Σchlordane (CHD) showed significant positive associations with cord or bloodspot TSH. At the same time, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorbenzene (HCB) showed negative associations with total T3 and total T4 in cord serum, respectively. Maternal exposure to β-hexachlorhexane (β-HCH), ΣCHD, ΣDDT, or p,p'-DDE were also associated with neonatal thyroid hormones. Although the sample size is small and the thyroid hormone levels of the subjects were within the reference range, our observation supports thyroid disrupting potential of several POPs among newborn infants, at the levels occurring in the general population. Considering the importance of thyroid hormones during gestation and early life stages, health implication of thyroid hormone effects by low level POPs exposure deserves further follow up investigations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mercury and lead are naturally occurring toxicants and are responsible for various health issues including neurobehavioral and developmental disorders. Because of crucial synchronized developmental ...processes occurring at the early stage of life, infancy and childhood are considered as among the most susceptible windows to the exposure to these metals. Breastmilk is often the only source of nutrition during the first months of life. As breastmilk can be contaminated with these metals, breastfeeding may serve as a significant route of heavy metal exposure among infants. In order to understand current levels of exposure to mercury and lead through breastfeeding, and their associated risks, a total of 157 lactating mothers were recruited from Children's Health and Environmental Chemicals of Korea (CHECK) cohort, and breastmilk samples were collected at 15 and 30days after delivery (n=207). Mercury was detected from 100% of breastmilk with a median concentration of 0.59μg/L, and lead was detected in 77% of the samples with a median at 4.71μg/L. Higher concentrations of lead were found in the 30- day breastmilk than in the 15-day. Up to 45% of the breastmilk samples exceeded the normal range of the breastmilk lead suggested by WHO. Based on Monte Carlo simulation, about 71% of 15days old infants and 56% of 30days old infants were estimated at risk due to lead exposure through breastfeeding. Considering vulnerability of infants and well-known neurological toxicity of these metals, further studies to identify major exposure sources that contribute the lead concentration in breastmilk and health implication of early life stage exposure to lead among the breastfed infants are warranted.
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•We analyzed mercury and lead in 207 breastmilk collected at 15 and 30days after delivery.•Mercury was detected from 100% of breastmilk with the median of 0. 59μg/L.•Lead was detected in 77 % of breastmilk with the median of 4.71μg/L.•The hazard quotient of lead exceeded 1.0 for 71% of 15days and for 56% for 30days old infants from breastfeeding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study aimed to examine the impact of term LBW on short-term neonatal and long-term neurodevelopmental outcomes in children 5-7 years of age. This is a population-based cohort study that merged ...national data from the Korea National Health Insurance claims and National Health Screening Program for Infants and Children. The participants were women who gave birth at a gestational age of ≥ 37 weeks between 2013 and 2015 in the Republic of Korea, and were tracked during 2020 for the neurodevelopmental surveillance of their children. Among 830,806 women who gave birth during the study period, 31,700 (3.8%) of their babies weighed less than 2500 g. By Cox proportional hazard analysis, children aged 5-7 years who had LBW were associated with any developmental, motor developmental delay, cognitive developmental delay, autism spectrum, attention deficit hyperactivity disorders, and epileptic and febrile seizures.Children born with term LBW were more vulnerable to neurodevelopmental disorders at 5-7 years of age than those with normal and large birth weights. This study further substantiates counseling parents regarding the long-term outcomes of children being born underweight.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Lead (Pb) and mercury (Hg) are neurodevelopmental toxicants that pose risks to cognitive and behavioral health. Given early childhood's vulnerability to these metals, understanding their sources and ...pathways of exposure during infancy is crucial for public health. During the weaning process, infants may be exposed to metals through the baby food they consume. We aimed to assess metal exposure through homemade weaning foods by analyzing 288 samples consumed by 157 Korean infants aged 6-, 9-, 12-, 15-, and 24–27 months. Pb was detected in 65 % of samples, with levels reaching up to 169 ng/g. Notably, 58 % exceeded the Maximum Level (ML) of 10 ng/g, with a median concentration of 14.7 ng/g fresh weight. Total Hg was found in 88 % of samples, with a median concentration of 4.56 ng/g fresh weight. Estimated median daily intakes of Pb and Hg were 0.29 and 0.09 μg/kg/d, respectively. Considering a benchmark dose for Pb (0.5 μg/kg/d by EFSA), 94 % (the margin of exposure <10) of all age groups was estimated to have a potential health concern associated with homemade baby food consumption. For Hg, only 6 % exceeded a hazard quotients of 1 compared to a provisional tolerable weekly intake for Hg (4 μg/kg/week by WHO). This study marks the first direct assessment of daily Pb and Hg intake through homemade baby food among Korean infants. Our findings underscore the urgent need for heightened awareness regarding metal exposure through homemade baby food.
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•Directly assessed Pb and Hg intake from homemade baby food in Korean infants•Found Pb in 65 % of homemade baby foods, with 58 % exceeding safe levels•Margin of Exposures (MOEs) for Pb constantly below 10 across all age groups•Based on Hg's Estimated Daily Intakes (EDIs), 6 % of infants face potential risks.•Homemade baby food emerges as a significant source of Pb and Hg exposure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) are of global concern because of their widespread ...contamination and adverse health effects. Potential endocrine disruption, especially of thyroid status by PCBs has been repeatedly suggested in both experimental and epidemiological studies. However the associations with PBDEs or OCPs have been arguable especially in human populations. We investigated the associations between major groups of POPs and thyroid hormone balances among pregnant women. One hundred five pregnant women at delivery were recruited from four cities of Korea in 2011 and were investigated. Blood samples were collected within a day before delivery. Serum was then analyzed for 19 PCBs, 19 PBDEs, and 19 OCPs, along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs such as PCB28, 52, and 118 showed negative associations with T3 or T4. BDE47 and total PBDEs showed significant associations with T3 or T4. For OCPs, dichlorodiphenyltrichloroethanes (DDTs) and hexachlorobenzene (HCB) were generally associated with reduction of T3 or T4. The thyroid hormone levels of all subjects were within the reference range, however exposure to several target POPs were clearly related with potential for disrupting thyroid hormone balance among pregnant women, at the current level of exposure. Although subtle, the changes in thyroid hormones should be seen with caution because even minor changes within pregnant women may have significant consequences especially on sensitive population like fetus.
•Associations between POPs and thyroid hormone levels were examined in pregnant women.•Several PCBs and OCPs are significantly associated with T3 or T4 levels.•PBDEs showed thyroid disrupting potential, but the directions were inconsistent.•Implications of POPs exposure on fetus during gestation deserve further investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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