Preeclampsia is a pregnancy complication which threatens the survival of mothers and fetuses. It originates from abnormal placentation, especially insufficient fusion of the cytotrophoblast cells to form the syncytiotrophoblast. In this study, we found that THBS1, a matricellular protein that mediates cell-to-cell and cell-to-matrix interactions, is downregulated during the fusion of primary cytotrophoblast and BeWo cells, but upregulated in the placenta of pregnancies complicated by preeclampsia. Also, THBS1 was observed to interact with CD36, a membrane signal receptor and activator of the cAMP signaling pathway, to regulate the fusion of cytotrophoblast cells. Overexpression of THBS1 inhibited the cAMP signaling pathway and reduced the BeWo cells fusion ratio, while the effects of THBS1 were abolished by a CD36-blocking antibody. Our results suggest that THBS1 signals through a CD36-mediated cAMP pathway to regulate syncytialization of the cytotrophoblast cells, and that its upregulation impairs placental formation to cause preeclampsia. Thus, THBS1 can serve as a therapeutic target regarding the mitigation of abnormal syncytialization and preeclampsia.
The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson’s disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher’s exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease’s pathophysiology but also suggest potential biomarkers for early disease detection.
Abstract Background: Obesity is associated with many adverse effects on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, ovarian function in obese women during early pregnancy still needs further assessment. Methods: Obesity was induced in C57BL6/J mice using high-fat diets (HFD) for 12 weeks; In vitro high-fat model was established with KGN cells treated with Oleate acid and Palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by Hematoxylin and Eosin staining and its function was assessed using ELISA, Western blotting and Immunohistochemistry. The Oil Red O staining and Transmission electron microscopy were used to detect fatty acid accumulation and specific markers relating to ovarian functional mechanism were assessed by Real time PCR, Western blotting, Lactate detection, ATP detection, Biochemical analyses and ELISA. Results: The results of this study showed that during early pregnancy, the number of corpus luteum, serum estradiol and progesterone levels, and the expression of genes CYP19A1, CYP11A1 and StAR, which are related to steroid biosynthesis, were significantly increased in HFD female mice. HFD-fed mice also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis ( Acsl4 and Elovl5 ) and fatty acid uptake and transport ( Slc27a4 ), together with the β-oxidation rate-limiting enzyme ( Cpt1a ) were significantly upregulated in HFD-fed mice. Specifically, there was abnormal elevation of ATP level and aberrant expression of tricarboxylic acid cycle (TCA) and electron transport chain related genes in the ovary of HFD pregnant mice . Treatment of KGN cells with etomoxir targeting β-oxidation of fatty acid, showed decrease tricarboxylic acid cycle and electron transport chain. The elevated ATP level and the increased estradiol and progesterone levels were reversed. Conclusions: This study indicated that during early pregnancy, high-fat diet and induced-obesity increased fatty acid β-oxidation, which in turn increase the tricarboxylic acid cycle and the electron transport chain, and consequently increases ATP production and ovarian dysfunction.
Object: COVID-19 pandemic and worldwide quarantine seriously affected the physical and mental health of the general public. Our study aimed to investigate the effects of the COVID-19 quarantine on pregnancy outcomes among pregnant women with hypertensive disorders of pregnancy (HDP). Methods: This single-center retrospective cohort study collected complete clinical data of HDP patients with a history of home quarantine in The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) in 2020 as well as the patients without home quarantine in 2018 and 2019. Then, the maternal and neonatal outcomes of two subtypes of HDP, gestational hypertension (GH) and preeclampsia/eclampsia (PE/E), were analyzed over the three years. Results: The incidence of HDP increased from 0.84% in 2018 and 0.51% in 2019 to 2.30% in 2020. The data suggested that home quarantine was associated with higher gestational weight gain, obesity rates, blood pressure, and uric acid among the patients with HDP in 2020. Furthermore, HDP patients with a history of home quarantine may have worse neonatal outcomes, including lower newborn weight, shorter body length, lower Apgar score, and higher risk of fetal growth restriction. Conclusion: Our results suggested that COVID-19 quarantine may be a risk factor for poor pregnancy outcomes in HDP patients. Lifestyle guidance and antenatal care may be necessary for HDP patients with home quarantine in an epidemic outbreak. Keywords: COVID-19, home quarantine, pregnancy outcomes, HDP, obesity
Obesity is associated with many adverse effects on female fertility. Obese women have a higher likelihood of developing ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, the effect of obesity on ovarian function during early pregnancy needs to be further assessed.C57BL6/J mice were given a high-fat diet (HFD) for 12 weeks to induce obesity. An in vitro high-fat model was established by treating the human ovarian granulosa cell line KGN with oleic acid and palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by hematoxylin and eosin staining and ovarian function was assessed by enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Oil Red O staining and transmission electron microscopy were used to detect fatty acid accumulation. Specific markers relating to the ovarian functional mechanism were assessed by real-time PCR, western blotting, lactate detection, adenosine triphosphate (ATP) detection, biochemical analyses, and enzyme-linked immunosorbent assay.The results of this study showed that during early pregnancy, the number of corpus lutea, serum estradiol and progesterone levels, and the expression of the steroid biosynthesis-related protein CYP19A1 (aromatase), CYP11A1 (cholesterol side chain cleavage enzyme), and StAR (steroidogenic acute regulatory protein), were significantly increased in HFD mice. Mice fed an HFD also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis (Acsl4 and Elovl5), and fatty acid uptake and transport (Slc27a4), together with the β-oxidation rate-limiting enzyme Cpt1a, were significantly upregulated in HFD mice. Specifically, there was abnormal elevation of ATP and aberrant expression of tricarboxylic acid cycle (TCA)- and electron transport chain (ETC)-related genes in the ovaries of pregnant HFD mice. KGN cells treated with etomoxir targeting β-oxidation of fatty acid showed decreased TCA cycle and ETC related gene expression. The elevation of ATP and estradiol and progesterone levels was reversed.During early pregnancy, HFD-induced obesity increases fatty acid β-oxidation, which in turn increases TCA cycle and ETC related gene expression, leading to increased ATP production and ovarian dysfunction.
Purpose: To evaluate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether rational use of drugs will change these impacts.Methods: This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching (PSM) was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period.Results: A total of 3161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, pre-eclampsia, fetal growth restriction (FGR), preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid.Conclusions: Home quarantine would increase the incidence of ICP and lead to adverse maternal and fetal outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should strengthen management and life guidance for women with ICP and speed up the development of home quarantine guidelines.Funding Information: This work was funded by the National Natural Science Foundation of China (grant numbers 81801458 and 81771614) and Program for Youth Innovation in Future Medicine, Chongqing Medical University (grant numbers W0068).Declaration of Interests: The authors declared that they have no conflict of interest.Ethics Approval Statement: This study was approved by the ethics committee of Chongqing Medical University (ID: 20220627). All participants provided informed consent, documented in an Excel file, and saved with a security code. The Ethics Committee also approved the procedure for verbal informed consent of our study. The Ethics Society of Clinical Scientific Research permitted the visiting and use of the medical records described in our study. All the procedures were performed following the ethical standards of the institutional research committee and the 1964 Helsinki declaration and its later amendments.
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