Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption.

The placenta is pivotal for fetal development and maternal-fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (ß: -103.8, 95% CI: -186.3 and -21.32) and 6:2 Cl-PFESA (ß: -80.04, 95% CI: -139.5 and -20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%-32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.

Parental Exposure to Environmentally Relevant Concentrations of Bisphenol-A Bis(diphenyl phosphate) Impairs Vascular Development in Offspring through DNA/RNA Methylation-Dependent Transmission.

Bisphenol-A bis(diphenyl phosphate) (BDP) has been increasingly detected in indoor environmental and human samples. Little is known about its developmental toxicity, particularly the intergenerational effects of parental exposure. In this study, adult zebrafish were exposed to BDP at 30-30,000 ng/L for 28 days, with results showing that exposure did not cause a transfer of BDP or its metabolites to offspring. Vascular morphometric profiling revealed that parental exposure to BDP at 30 and 300 ng/L exerted significant effects on the vascular development of offspring, encompassing diverse alterations in multiple types of blood vessels. N6-Methyladenosine (m6A) methylated RNA immunoprecipitation sequencing of larvae in the 300 ng/L group revealed 378 hypomethylated and 350 hypermethylated m6A peaks that were identified in mRNA transcripts of genes crucial for vascular development, including the Notch/Vegf signaling pathway. Concomitant changes in 5 methylcytosine (m5C) DNA methylation and gene expression of m6A modulators (alkbh5, kiaa1429, and ythdf1) were observed in both parental gonads and offspring exposed to BDP. These results reveal that parental exposure to low concentrations of BDP caused offspring vascular disorders by interfering with DNA and RNA methylation, uncovering a unique DNA-RNA modification pattern in the intergenerational transmission of BDP's developmental toxicity.

Maternal exposure to nano-titanium dioxide impedes fetal development via endothelial-to-mesenchymal transition in the placental labyrinth in mice.

BACKGROUND: Extensive production and usage of commercially available products containing TiO2 NPs have led to accumulation in the human body. The deposition of TiO2 NPs has even been detected in the human placenta, which raises concerns regarding fetal health. Previous studies regarding developmental toxicity have frequently focused on TiO2 NPs < 50 nm, whereas the potential adverse effects of large-sized TiO2 NPs received less attention. Placental vasculature is essential for maternal-fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO2 NPs (100 nm in size) on the placenta and fetal development and elucidates the underlying mechanism from the perspective of placental vasculature. Pregnant C57BL/6 mice were exposed to TiO2 NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5-16.5. RESULTS: TiO2 NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO2 NP-exposed groups exhibited a dose-dependent decrease in body weight and length, as well as in placental weight and diameter. In vivo imaging showed an impaired placental barrier, and pathological examinations revealed a disrupted vascular network of the labyrinth upon TiO2 NP exposure. We also found an increase in gene expression related to the transforming growth factor-ß (TGF-ß) -SNAIL pathway and the upregulation of mesenchymal markers, accompanied by a reduction in endothelial markers. In addition, TiO2 NPs enhanced the gene expression responsible for the endothelial-to-mesenchymal transition (EndMT) in cultured human umbilical vein endothelial cells, whereas SNAIL knockdown attenuated the induction of EndMT phenotypes. CONCLUSION: Our study revealed that maternal exposure to 100 nm TiO2 NPs disrupts placental vascular development and fetal mice growth through aberrant activation of EndMT in the placental labyrinth. These data provide novel insight into the mechanisms of developmental toxicity posed by NPs.

Environmentally relevant concentrations of fipronil selectively disrupt venous vessel development in zebrafish embryos/larvae.

The pesticide fipronil is widely dispersed in aquatic environments and frequently detected in the general population. Although the adverse effects on embryonic growth by fipronil exposure have been extensively documented, the early responses for its developmental toxicity are largely unknown. In the present study, we explored the sensitive targets of fipronil, focusing on vascular injury using zebrafish embryos/larvae and cultured human endothelial cells. Exposure to 5-500 µg/L fipronil at the early stage impeded the growth of sub-intestinal venous plexus (SIVP), caudal vein plexus (CVP), and common cardinal veins (CCV). The damages on venous vessels occurred at exposure to the environmentally relevant concentration as low as 5 µg/L fipronil, whereas no significant change was observed in general toxicity indexes. In contrast, vascular development of the dorsal aorta (DA) or intersegmental artery (ISA) was not affected. In addition, the mRNA levels of vascular markers and vessel type-specific function genes exhibited significant decreases in venous genes, including nr2f2, ephb4a, and flt4, but no appreciable change in arterial genes. Likewise, the more pronounced changes in cell death and cytoskeleton disruption were shown in human umbilical vein endothelial cells as compared with human aortic endothelial cells. Furthermore, molecular docking supported a stronger affinity of fipronil and its metabolites to the proteins correlated with venous development, such as BMPR2 and SMARCA4. These results reveal the heterogeneity in developing vasculature responsive to fipronil's exposure. The preferential impacts on the veins confer higher sensitivity, allowing them to be appropriate targets for monitoring fipronil's developmental toxicity.

Age-, period- and cohort-specific incidence of sexually transmitted diseases in Yantian District from 2008 to 2022 / 预防医学

Objective@#To investigate the incidence trend of sexually transmitted diseases (STDs) in Yantian District, Shenzhen City, Guangdong Province from 2008 to 2022, and the effects of age, period, and cohort on STDs incidence, so as to provide the basis for formulating control measures for STDs.@*Methods@#Data of reported STDs cases (syphilis, gonorrhea, genital Chlamydia trachomatis infections, condyloma acuminatum and genital herpes) among population aged 15 to 64 years in Yantian District from 2008 to 2022 were collected through the Chinese Disease Control and Prevention Information System. The temporal and population distribution of STDs were descriptively analyzed. Trends in incidence of STDs were analyzed using average annual percent change (AAPC). Impacts of age, period and cohort on the incidence of STDs were analyzed by an age-period-cohort model.@*Results@#A total of 6 156 cases of STDs aged 15 to 64 years were reported from 2008 to 2022, and the average annual incidence was 229.92/105. The overall incidence showed an upward trend (AAPC=2.409%, P<0.05), and an upward trend among females (AAPC=5.846%, P<0.05), but the trend was not statistically significant among males (AAPC=0.193%, P>0.05). The incidence of STDs showed an increasing trend followed by a decreasing trend with the increase of age. The incidence trend among males was consistent with the overall population, reaching its peak in the age group of 30 to 34 years (371.04/105), while the incidence among females showed an increasing trend with the increase of age, peaking in the age group of 60 to 64 years (442.15/105). Compared with 2013-2017, the incidence risk of STDs showed an increasing trend in 2018-2022 (RR=1.349, 95%CI: 1.217-1.495). Compared with the birth cohort of 1975-1979, the incidence risk of STDs in 1980-2005 birth cohort showed an increasing trend, with the highest incidence risk in 2000-2004 birth cohort (RR=4.178, 95%CI: 2.717-6.423).@*Conclusions@#The overall incidence of STDs among residents aged 15 to 64 years in Yantian District from 2008 to 2022 appeared a tendency towards a rise. Age, period and cohort all had impacts on the incidence, with a greater effect among females than males.

Analysis of the demand and influencing factors for children’s sexual education knowledge among rural parents / 中国学校卫生

Objective@#To understand the demand of rural parents for children’s sexual education knowledge and associated factors, to provide reference and advise for the development of the children’s sexual education in the rural areas.@*Methods@#In this study,1 015 parents from 16 rural kindergartens in Luzhou City and Mianyang City were selected as the research objects by multiple-stage stratified sampling from March to May, 2019. The self-interview or face-to-face questionnaire survey was used to investigate the demand for children’s sexual education among parents.@*Results@#Totally 81.7%(829) of parents expressed their demand for children’s sexual education knowledge. Multivariate logistic regression analysis showed that age was negatively associated with demand for sexual education of children(OR=0.73,95%CI=0.61-0.88). Junior middle school education background of mothers(OR=2.45,95%CI=1.36-4.41), received sexual education for children(OR=2.85，95%CI=1.84-4.42), reckon sexual education for children as necessary(OR=4.97，95%CI=3.16-7.83)and regarded it as parents’ own responsibility(OR=2.11，95%CI=1.30-3.43) had a high demand for children’s sexual education knowledge(P<0.05).@*Conclusion@#Parents in Sichuan rural areas generally have a high demand for children’s sexual education. We should intensify publicity and training about sexual education knowledge among parents in rural areas and attach importance to the cooperation between family and kindergarten in order to jointly promote the development of children’s sexual education.

Sex-related knowledge and behavior among children in senior grade of kindergarten in rural areas fo Sichuan Province / 中国学校卫生

Objective@#To analyze the level of sex-related knowledge and behavior and related factors among children in senior grade of kindergarten in rural areas, and to provide the evidence for early childhood sexuality education.@*Methods@#Multi-state stratified sampling method was adopted. From March to May 2019,a total of 324 students and their parents from 16 kindergartens of rural areas in Sichuan Province were enrolled, self-developed questionnaire was used to collect the basic demographic characteristics, information of sexuality education knowledge and sex-related behavior.@*Results@#The average score of sexuality education knowledge was 5(4,6) point, and the awareness rate was 33.6%(109). The qualified sex-related behavior was observed in 75.0%(243 of all the children), while 25.0%(81) needed to be improved. Multivariate analysis showed that,compared with children were aware of the sexuality education knowledge, children who were unaware of the sexuality education knowledge were more likely to have good sex-related behavior, with the OR(95%CI) value was 2.06(1.14-3.72). The possibility of having good sex-related behavior among those children with more than 2 members in the family parents carring out sexuality education was higher than children without sexuality education in the family, with the OR(95%CI) value being 2.40(1.17-4.89).@*Conclusion@#The level of sexuality education knowledge among children in senior grade of kindergarten of rural areas in Sichuan is low, and most children s behavior needs to be improved. Children s awareness of sexuality education knowledge and the number of family members who have carried out sexuality education are related to the occurrence of children s sex-related behavior.