Prenatal and Perinatal per- and polyfluoroalkyl substances (PFAS) exposure and birth outcomes and fetal development.
Prenatal and perinatal exposure to Per- and polyfluoroalkyl substances (PFAS)-contaminated drinking water impacts offspring neurobehavior and development
M. J. Marchese, T. Zhu, A. B. Hawkey, K. Wang, E. Yuan, J. Wen, S. E. Be, E. D. Levin, L. Feng
Our post-weaning behavioral measures of anxiety, depression, and memory were not found to be affected by maternal PFAS exposure. In adolescence (week five) and adulthood (week eight), the high PFAS dose significantly attenuated typical sex differences in locomotor activity. Maternal exposure to an environmentally relevant PFAS mixture produced developmental delays in the domains of pup weight, anogenital distance, and reflex acquisition for rat offspring. The high-dose PFAS exposure significantly decreased typical sex differences in locomotor activity.
Maternal exposure to perfluorobutane sulfonate (PFBS) during pregnancy: evidence of adverse maternal and fetoplacental effects in New Zealand White (NZW) rabbits
C. E. Crute, C. D. Landon, A. Garner, S. M. Hall, J. I. Everitt, S. Zhang, B. Blake, D. Olofsson, H. Chen, H. M. Stapleton, S. K. Murphy, L. Feng MJ; Zhu, T; Hawkey, AB; Wang, K; Yuan, E; Wen, J; Be, SE; Levin, ED; Feng, L
PFBS-high dose dams exhibited significant changes in blood pressure markers, seen through increased pulse pressure and renal resistive index measures, as well as kidney histopathological changes. Fetuses from these dams showed decreased crown-rump length. Statistical analysis of placental weight identified a significant interaction term between PFBS high dose and fetal sex, suggesting a sex-specific effect on placental weight. RNA sequencing identified the dysregulation of angiotensin (AGT) in PFBS high-dose placentas. These results suggest that PFBS exposure during gestation leads to adverse maternal outcomes, such as renal injury and hypertension, and fetal outcomes, including decreased growth parameters and adverse placenta function. These outcomes raise concerns about pregnant women’s exposure to PFBS and pregnancy outcomes.
Perfluoroalkyl and polyfluroalkyl substances and maternal thyroid hormones in early pregnancy
R. Aimuzi, K. Luo, R. Huang, X. Huo, M. Nian, F. Ouyang, Y. Du, L. Feng, W. Wang, J. Zhang; Shanghai Birth Cohort Study
Results: Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) were positively associated with FT4. Perfluorononanoic acid (PFNA) and PFHxS were positively associated with FT3, while PFHxS was negatively associated with TSH. TPOAb-positivity appeared to modify the associations between PFAS and THs. In TPOAb-positive women, several long-chain PFAS were positively associated with FT4 and/or FT3 and tended to be negatively associated with TSH.
Conclusions: Several long-chain PFAS were associated with disrupted TH homeostasis in Chinese pregnant women, especially among TPOAb-positive women.
Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells
W. Marinello, L. Feng, T. K. Allen
We found that PFBS exposure interrupted cell proliferation and invasion dose-dependently. Transcriptome analysis identified dysregulated HIF-1a target genes relevant to cell proliferation/invasion and preeclampsia
Our findings demonstrate that medroxyprogesterone acetate exerts its anti-inflammatory effect primarily through the glucocorticoid receptor in human amnion mesenchymal cells. Modulation of glucocorticoid receptor signaling pathways maybe a useful therapeutic strategy for preventing inflammation induced fetal membrane weakening leading to preterm premature rupture of membranes.
Perfluoroalkyl substances in early pregnancy and risk of hypertensive disorders of pregnancy: A prospective cohort study
X. Huo, R. Huang, Y. Gan, K. Luo, R. Aimuzi, M. Nian, J. Ao, L. Feng, Y. Tian, W. Wang, W. Ye, J. Zhang; Shanghai Birth Cohort
Results: Among all singleton live births, the incidence rates of GH and PE were 2.0% and 2.2%, respectively. Overall, PFASs did not show a significant and consistent pattern of the associations with GH, PE or overall HDP, both before and after controlling for potential confounders. ENR model confirmed the results that there was no independently predictive role of PFASs on GH, PE or overall HDP.
Conclusions: In this large prospective cohort study, maternal plasma concentration of PFASs in early pregnancy were not associated with GH, PE or overall HDP in singleton livebirths.
Perfluoroalkyl and polyfluoroalkyl substances and fetal thyroid hormone levels in umbilical cord blood among newborns by prelabor caesarean delivery
R. Aimuzi, K. Luo, Q. Chen, H. Wang, L. Feng, F. Ouyang, J. Zhang
Results: In SPLS analyses, thyroid stimulating hormone (TSH) level decreased with increasing concentrations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUA) and perfluorododecanoic acid (PFDoA). Moreover, we found a positive association between PFDoA and free thyroxine (FT4) levels after adjusting for potential confounders. Free tri-iodothyronine (FT3) levels were positively associated with concentrations of PFOS, but negatively associated with PFDoA. We also observed gender disparity in the associations of PFAS exposure and FT3, FT4, TSH levels.
Conclusion: Our results suggest that prenatal exposure to certain PFAS may disrupt fetal thyroid function. The effect may be gender-specific.
Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances(PFAS) and the risk of hypertensive disorders of pregnancy
R. Huang, Q. Chen, L. Zhang, K. Luo, L. Chen, S. Zhao, L. Feng, J. Zhang
Results: The risk of gestational hypertension and preeclampsia was 3.3% and 2.8% in our subjects, respectively. Perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluoroundecanoic acid (PFUA) were associated with preeclampsia based on elastic net penalty regression. In the fully adjusted statistical model, women with a higher level of standardized ln-transformed PFBS had an increased odds of preeclampsia and overall HDP.
Conclusion: Prenatal exposure to PFBS and other PFAS were positively associated with the risk of preeclampsia and overall HDP.
The biology of placental development and the roles of placental molecular signals in reproduction and neurobehavioral development in offspring using placental-specific knockout mouse models.
Longitudinal intravital imaging of mouse placenta
X. Zhu, Q. Huang, L. Jiang, V.-T. Nguyen, T. Vu, G. Devlin, J. Shaima, X. Wang, Y. Chen, L. Ma, K. Xiang, E. Wang, Q. Rong, Q. Zhou, Y. Kang, A. Asokan, L. Feng, S.-W. D. Hsu, X. Shen, J. Yao
Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy.
Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.
Progesterone receptor membrane component 2 is critical for human placental extravillous trophoblast invasion
T. Yokouchi-Konishi, Y. Liu, L. Feng
Proper extravillous trophoblast invasion is essential for normal placentation and pregnancy. However, the molecular mechanisms by which cytotrophoblasts differentiate into extravillous trophoblast are unclear
We discovered that the attenuation of progesterone receptor membrane component 2 plays a role in placentation by promoting cell proliferation, invasion, and angiogenesis in extravillous trophoblasts via activation of hypoxia-inducible factor 1 alpha signaling. We thus identified a new function of progesterone receptor membrane component 2 and provide insights on understanding the mechanisms of trophoblast invasion.
BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation
B. Liu, Y. Liu, S. Li, P. Chen, J. Zhang, L. Feng
Background: Brain-derived neurotrophic factor (BDNF) plays an important role in ovarian function including follicle development and oocyte maturation, and embryonic development. However, whether BDNF treatment can reimpose ovarian aging and impaired fertility remains elusive.
Conclusion: We demonstrated that ten consecutive days of daily IP injection of rhBDNF rescued ovarian function in aged mice. Our results further indicate that TrkB and cyclin D1-creb signaling may underlie the BDNF function in ovaries. Targeting BDNF-TrkB signaling is a potential novel therapeutic strategy to reverse ovarian aging.
Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion
Y. Zhang, P. Liang, L. Yang, K. Z. Shan, L. Feng, Y. Chen, W. Liedtke, C. B. Coyne, H. Yang
TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear.
Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events.
TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development
Y. Zhang, T. Le, R. Grabau, Z. Mohseni, H. Kim, D. R. Natale, L. Feng, H. Pan, H. Yang
Cell-cell fusion or syncytialization is fundamental to the reproduction, development, and homeostasis of multicellular organisms. In addition to various cell type–specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell fusion events. Nevertheless, the molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear.
Our findings provide insight into understanding cell-cell fusion mechanism of other cell types and on mitigating pregnancy complications such as miscarriage, intrauterine growth restriction, and preeclampsia.
Other endocrine disrupting chemicals exposures and birth outcomes and health in offspring
Effects of maternal urban particulate matter SRM 1648a exposure on birth outcomes and offspring growth in mice
S. Li, B. Liu, Y. Liu, Y.-Q. Ding, J. Zhang, L. Feng
The association between exposure to particulate matter (PM) during pregnancy and abnormal birth outcomes is still inconclusive. This study aims to provide more evidence for this public health concern by investigating birth outcomes and the growth of offspring in mice exposed to PM during pregnancy.
Our study indicated that maternal exposure to PM did not significantly impact birth outcomes of C57BL/6 J mice but affected growth trajectories in offspring after birth in a dose- and fetal sex-dependent manner.
Maternal urban particulate matter exposure and signaling pathways in fetal brains and neurobehavioral development in offspring
S. Li, Y. Liu, B. Liu, Y.-Q. Hu, Y.-Q. Ding, J. Zhang, L. Feng
It is well understood that exposure to particulate matter (PM) can have adverse effects on the nervous system. When pregnant women are exposed to PM, their fetuses are also affected through the placenta. However, the mechanisms by which fetal brain development is regulated between mother and fetus remain unclear.
Our study demonstrated that prenatal PM exposure enhanced exploration and locomotor activity in adolescent offspring and altered molecular events in maternal brain, fetal brain, and placenta. The connections of these changes warrant further investigations.
Transcriptomics integrated with metabolomics reveals the effect of Bisphenol F (BPF) exposure on intestinal inflammation
Y. Liu, W. Tang, J. Ao, J. Zhang, L. Feng
As a viable alternative to Bisphenol A (BPA), Bisphenol F (BPF) has been detected in humans at comparable concentrations and detection frequencies. Emerging evidence reveals that BPF induces intestinal toxicity. However, less information is available concerning BPF and its potential effects on intestinal inflammation, which has been associated with numerous disorders.
Data presented herein provide evidence for the possible roles of BPF in the pathogenesis of intestinal inflammation. These results illustrate the advantages of using integrative analyses of high throughput datasets for characterizing the effects and mechanisms of toxicants.
Association between triclocarban and triclosan exposures and the risks of type 2 diabetes mellitus and impaired glucose tolerance in the National Health and Nutrition Examination Survey
Background: There has been increasing interest in the concept that exposure to environmental chemicals may be contributing factors to epidemics of diabetes mellitus (DM). Triclocarban and triclosan (TCs) are synthetic antibacterial chemicals that are widely used in personal care products. Studies have shown that TCs are endocrine disruptors that alter metabolic conditions. However, it remains unclear whether exposure to TCs is a risk factor for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM).
Results: Nine hundred US participants were included in the analysis, of whom 242 were diagnosed with T2DM and 117 had IGT. Among women, there was a significant positive association between triclocarban, but not triclosan exposure and T2DM after adjusting for potential confounding factors. Among men, no significant association between TCs exposure and IGT or T2DM was observed.
Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2
Y. Ye, Y. Tang, Y. Xiong, L. Feng, X. Li
Preeclampsia leads to adverse outcomes for pregnant women. Bisphenol A (BPA) is an environmental endocrine disruptor and has been shown to be positively associated with increased risk of preeclampsia in human studies. We investigated whether BPA exposure causes preeclampsia-like features in pregnant mice and the associated underlying mechanisms.
Our results suggest that this phenomenon involves the epigenetic reprogramming and down-regulation of WNT2 mediated by DNMT1. Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2.
Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study
Y. Ye, Q. Zhou, L. Feng, J. Wu, Y. Xiong, X. Li
Background: Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia.
Conclusions: These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia.
Maternal Urinary Triclosan Concentration in Relation to Maternal and Neonatal Thyroid Hormone Levels: A Prospective Study
Y. Ye, Q. Zhou, L. Feng, J. Wu, Y. Xiong, X. Li
Background: Triclosan (TCS) is a synthetic antibacterial chemical widely used in personal care products. TCS exposure has been associated with decreased thyroid hormone levels in animals, but human studies are scarce and controversial.
Conclusions: Our results suggest significant inverse associations between maternal urinary TCS and cord blood FT3 as well as maternal blood FT4 concentrations at third trimester.
