Bisphenol A (BPA) accumulation in the placenta leads to fetal growth restriction (FGR). Here we aimed to explore the effect and the underlying mechanism of BPA exposure on fetal development. ELISA ...was performed to measure estrogen levels in human placenta and BeWo cells. qRT-PCR and Western blotting were conducted to determine the expression of estrogen receptors (ERs), breast cancer resistance protein (BCRP), the key enzymes for ER synthesis, and DNA methyltransferases (DNMTs). Bisulfite-sequencing PCR analysis was performed to measure CpG methylation in ER genes. Flow cytometry was used to examine cell apoptosis. We found that human FGR placentae had significantly increased BPA and estrogen levels and decreased BCRP levels compared with healthy placentae. BPA downregulated BCRP expression via ERs, and BCRP silencing promoted ER expression in BeWo cells. Compared with vehicle treatment, BPA treatment significantly enhanced the expression of key enzymes for estrogen synthesis and ERs in BeWo cells. BPA treatment inhibited CpG methylation in ER genes, along with downregulated DNMT1 expression and upregulated DNMT3a and DNMT3b expression. BPA treatment significantly promoted BeWo cell apoptosis compared with vehicle treatment. Importantly, ER inhibitor ICI-182780 significantly reversed all the BPA-induced effects on BeWo cells. In conclusion, BPA promotes estrogen production and cell apoptosis in BeWo cells via upregulating ER expression, leading to FGR.
•Human FGR placentae had increased BPA and estrogen levels and decreased BCRP levels.•BPA downregulated BCRP expression via ERs.•BCRP silencing promoted ER expression in BeWo cells.•ER inhibitor ICI-182780 reversed all the BPA-induced effects on BeWo cells.
•Intracellular Ca2+ level is dynamics during mammalian erythropoiesis.•Ca2+-driven signaling regulates erythroid differentiation.•Ca2+ homeostasis provides new therapeutic opportunities in erythroid ...disorders.
Calcium (Ca2+) is an important second messenger molecule in the body, regulating cell cycle and fate. There is growing evidence that intracellular Ca2+ levels play functional roles in the total physiological process of erythroid differentiation, including the proliferation and differentiation of erythroid progenitor cells, terminal enucleation, and mature red blood cell aging and clearance. Moreover, recent research on the pathology of erythroid disorders has made great progress in the past decades, indicating that calcium ion hemostasis is closely related to ineffective erythropoiesis and increased sensitivity to stress factors. In this review, we summarized what is known about the functional roles of intracellular Ca2+ in erythropoiesis and erythrocyte-related diseases, with an emphasis on the regulation of the intracellular Ca2+ homeostasis during erythroid differentiation. An understanding of the regulation roles of Ca2+ homeostasis in erythroid differentiation will facilitate further studies and eventually molecular identification of the pathways involved in the pathological process of erythroid disorders, providing new therapeutic opportunities in erythrocyte-related disease.
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The endometrial basal layer is essential for endometrial regeneration, whose disruption leads to thin endometrium or intrauterine adhesion (IUA) with an unsatisfactory prognosis. Emerging data ...indicate that platelet-rich plasma (PRP) can promote endometrial proliferation, but the mechanism by which PRP regulates endometrial regeneration remains unclear. Herein, we investigated the therapeutic effects and possible mechanisms of PRP on endometrial regeneration. IUA animal model was generated by sham, mechanically damaging endometrium with or without PRP for 10 days. The uterine section in the model group showed degenerative changes with a narrow endometrial lumen, atrophic columnar epithelium, decreased number of endometrial glands, decreased endometrial thickness, and increased collagen deposition. The above disruption could be ameliorated by the PRP. Transcriptome sequencing analysis displayed that the retinol metabolism pathway and extracellular matrix (ECM) receptor interaction pathway were up-regulated and enriched in differential expression genes (DEGs). Melanotransferrin (MELTF) was the key up-regulated gene in PRP-induced endometrial regeneration, which was verified in vivo and in vitro. Ferroptosis, autophagy, and pyroptosis were down-regulated in PRP-treated Ishikawa cells. Conclusively, PRP promotes endometrium regeneration by up-regulating the retinol metabolism and ECM receptor interaction pathway with MELTF. Meanwhile, PRP could also inhibit endometrial epithelial cell death by regulating ferroptosis, autophagy, and pyroptosis.
An efficient N-heterocyclic carbene (NHC)-catalyzed asymmetric 3 + 4 annulation reaction of N-Ts hydrazones with 2-bromoenals has been developed. A series of functionalized ...tetrahydro-1H-1,2-diazepines with two consecutive stereocenters was obtained using NHCs as the catalyst in good yields with excellent diastereo- and enantioselectivities.
Endocrine-disrupting chemicals (EDCs) are suspected to be associated with endometriosis (EMs). This study aimed to synthesize published data and evaluate the relationship between four classic EDCs ...exposure and the risk of EMs. A systematic literature search for original peer reviewed papers was performed in the databases PubMed, EMBASE, and Web of Science based on inclusion criteria up to January 2018. Subsequently, a total of 20 papers conducting 30 studies fulfilled the eligibility criteria and were included in this meta-analysis (four studies for bisphenol A (BPA), 12 studies for polychlorinated biphenyls (PCBs), eight studies for organochlorine pesticides (OCPs), and six studies for phthalate esters (PAEs)). The overall odds ratio (OR) across all exposures and EMs was 1.41 (95% confidence interval (CI): 1.23-1.60). When assessing four specific chemicals, respectively, consistent increases in the risk of EMs were found in PCBs group (OR = 1.58; 95% CI: 1.18-2.12), OCPs group (OR = 1.40; 95% CI: 1.02-1.92) and PAEs group (OR = 1.27; 95% CI: 1.00-1.60), while BPA showed no significant association with EMs. Besides, in the di-(2-ethylhexyl)-phthalate (DEHP) group - the most commonly used PAEs, significant risk was also found (OR = 1.42; 95% CI: 1.19-1.70). The current meta-analysis strengthens the evidence that specific EDCs or their metabolites may promote the occurrence of EMs.
Congenital heart disease (CHD) is well established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive ...prenatal diagnosis of fetal CHD. This study used data-independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9%, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD.
Graphical abstract
Congenital heart disease (CHD) is well-established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. We used data independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9 %, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD
Objective
To provide clinical management guidelines for novel coronavirus (COVID‐19) in pregnancy.
Methods
On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and ...researchers was held and medical management strategies of COVID‐19 infection in pregnancy were discussed.
Results
Ten key recommendations were provided for the management of COVID‐19 infections in pregnancy.
Conclusion
Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal–fetal status.
Currently, there is no clear evidence regarding optimal delivery timing or route of delivery for pregnant women with COVID‐19 infection; these should be individualized based on obstetrical indications and maternal–fetal status.
It is known that inhibiting 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression in the placenta can cause fetal over-exposure to maternal glucocorticoids and induce intrauterine growth ...restriction (IUGR); these effects ultimately increase the risk of adult chronic diseases. This study aimed to investigate the molecular mechanism of the prenatal ethanol exposure (PEE)-induced inhibition of placental 11β-HSD2 expression. Pregnant Wistar rats were intragastrically administered ethanol (4 g/kg/d) from gestational days 9 to 20. The levels of maternal and fetal serum corticosterone and placental 11β-HSD2-related gene expression were analyzed. Furthermore, we investigated the mechanism of reduced placental 11β-HSD2 expression induced by ethanol treatment (15–60 mM) in HTR-8/SVneo cells. In vivo, PEE decreased fetal body weights and increased maternal and fetal serum corticosterone and early growth response factor 1 (EGR1) expression levels. Moreover, histone modification changes (decreased acetylation and increased di-methylation of H3K9) to the HSD11B2 promoter and lower 11β-HSD2 expression levels were observed. In vitro, ethanol decreased cAMP/PKA signaling and 11β-HSD2 expression and increased EGR1 expression in a concentration-dependent manner. A cAMP agonist and EGR1 siRNA reversed the ethanol-induced inhibition of 11β-HSD2 expression. Together, PEE reduced placental 11β-HSD2 expression, and the underlying mechanism is associated with ethanol-induced histone modification changes to the HSD11B2 promoter through the cAMP/PKA/EGR1 pathway.
•Impaired placental 11β-HSD2 involves in PEE-induced IUGR.•cAMP/PKA/EGR1 pathway is proposed to inhibit placental 11β-HSD2 expression.•Histone modifications are involved in ethanol-inhibited 11β-HSD2 expression.
Bisphenol-A (BPA) is a common environmental toxicant that is known to be associated with fetal growth restriction (FGR). However, the mechanisms of how BPA induce FGR is poorly characterized. We ...conducted proteomics to identify the abnormal expression of SRB1 in female placental tissues with high BPA-induced FGR and further verified its decreased expression in human placenta and BeWo cells. Next, the effect of BPA on fetal development was further confirmed in pregnant C57BL/6 mice. The expression of SRB1 was consistently downregulated in human FGR placentas, BPA-exposed trophoblasts and mouse placentas. In addition, we found that SRB1 interacted with PCNA, and BPA exposure indirectly reduced the expression of PCNA and further inhibited placental proliferation. In vitro studies showed that BPA exposure reduced the expression of CDK1, CDK2, cyclin B and phosphorylated Rb in placental trophoblast cells, indicating cell cycle arrest after exposure to BPA. In addition, the expression of γ-H2AX and phosphorylated ATM was upregulated in BPA-exposed trophoblasts, indicating increased DNA damage. Our results indicate that BPA-induced FGR is achieved by reducing the expression of SRB1, inhibiting placental proliferation and increasing DNA damage. Our findings not only explain the mechanism of BPA-associated developmental toxicity but also shed light upon developing novel therapeutic targets.
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