Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway

Article Biochemistry & Molecular Biology

Inhibition of GCN2 alleviates hepatic steatosis and oxidative stress in obese mice: Involvement of NRF2 regulation

Juntao Yuan et al.

Summary: The development of nonalcoholic fatty liver disease (NAFLD) is associated with the regulation of NRF2 by GCN2, which can attenuate hepatic steatosis and oxidative stress.

REDOX BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Gestational cholestasis induced intrauterine growth restriction through triggering IRE1α-mediated apoptosis of placental trophoblast cells

Xing-Xing Gao et al.

Summary: This study revealed that gestational cholestasis induces apoptosis of trophoblast cells in the placenta, leading to placental insufficiency and IUGR. Furthermore, the activation of the IRE1α pathway was found in cholestasis cases.

FASEB JOURNAL (2022)

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Article Gastroenterology & Hepatology

Pregnancy-Associated Liver Diseases

Norah A. Terrault et al.

Summary: Liver disorders unique to pregnancy are important due to their significant impact on maternal and fetal/neonatal morbidity and mortality. Prompt diagnosis and multidisciplinary care are crucial to minimize risks for pregnant women and their babies.

GASTROENTEROLOGY (2022)

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Article Environmental Sciences

Differential expression of placental 11β-HSD2 induced by high maternal glucocorticoid exposure mediates sex differences in placental and fetal development

Pengxia Yu et al.

Summary: This study demonstrates that high maternal glucocorticoids can regulate the expression of placental 11β-HSD2 in a sex-specific manner, resulting in differences in placental and fetal development.

SCIENCE OF THE TOTAL ENVIRONMENT (2022)

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Article Biochemistry & Molecular Biology

Substance P Hinders Bile Acid-Induced Hepatocellular Injury by Modulating Oxidative Stress and Inflammation

Dahyeon Lee et al.

Summary: This study investigated the effect of substance P (SP) on liver injury caused by cholestatic stress due to excessive bile acid accumulation. The results showed that SP reduced the damage of bile acids to hepatocytes and liver sinusoidal endothelial cells, possibly by modulating oxidative stress and inflammation to protect the cells.

ANTIOXIDANTS (2022)

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Article Obstetrics & Gynecology

Predictive Value of Serum Cholic Acid and Lithocholic Acid for the Diagnosis in an Intrahepatic Cholestasis of Pregnancy Population with High Levels of Total Bile Acids and the Correlation with Placental Hypoxia-Inducible Factor-1α

Chu-Yun Cheng et al.

Summary: This study found that serum cholic acid and lithocholic acid can be used as predictive diagnostic indicators for intrahepatic cholestasis of pregnancy, and the combined evaluation is associated with adverse perinatal outcomes. Cholic acid and lithocholic acid are positively correlated with placental HIF-1α expression levels.

INTERNATIONAL JOURNAL OF WOMENS HEALTH (2022)

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Review Biochemistry & Molecular Biology

Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients-A Systematic Review

Daniel Adon Mapamba et al.

Summary: NAC may have a positive impact on the treatment of TB, but current research lacks sufficient evidence to support its overall effects, requiring more clinical trials for validation.

ANTIOXIDANTS (2022)

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Article Obstetrics & Gynecology

Beyond stillbirth: association of intrahepatic cholestasis of pregnancy severity and adverse outcomes

Minhazur Sarker et al.

Summary: The severity of intrahepatic cholestasis of pregnancy is associated with adverse obstetrical outcomes, including spontaneous preterm labor, iatrogenic preterm birth, and meconium-stained amniotic fluid.

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY (2022)

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Article Environmental Sciences

Mitochondrial ROS-mediated ribosome stalling and GCN2 activation are partially involved in 1-nitropyrene-induced steroidogenic inhibition in testes

Jian Li et al.

Summary: In this research, it was discovered that acute exposure to 1-nitropyrene (1-NP) from polluted atmosphere resulted in a decline in testosterone (T) level in men. The study found that the reduction of T contents was caused by the downregulation of steroidogenic proteins in mouse testes and Leydig cells. The mechanism involved the activation of GCN2 and mitochondrial ROS-mediated ribosome stalling, leading to the inhibition of steroidogenic activity.

ENVIRONMENT INTERNATIONAL (2022)

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Article Obstetrics & Gynecology

Placental weight and size in relation to fetal growth restriction: a case-control study

Hong-Jiao Liu et al.

Summary: Reductions in placental weight and size are associated with decreased birth weight and increased odds of fetal growth restriction (FGR). These associations are more significant in male fetuses.

JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE (2021)

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Article Obstetrics & Gynecology

Cholestasis: A Prospective Study of Perinatal Outcomes and Time to Symptom Improvement

Casey S. Yule et al.

Summary: This study aimed to examine perinatal outcomes of women with intrahepatic cholestasis of pregnancy (ICP), finding that ICP patients had no significant differences in age, parity, mode of delivery, preeclampsia, or stillbirth compared to non-ICP patients and the general population, but preterm birth was significantly associated with ICP. The risk of spontaneous preterm birth increased significantly with severity of ICP, and time to symptom improvement also increased with worsening severity of the disease.

AMERICAN JOURNAL OF PERINATOLOGY (2021)

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Article Medicine, General & Internal

P-gp expression inhibition mediates placental glucocorticoid barrier opening and fetal weight loss

Caiyun Ge et al.

Summary: This study revealed that P-gp plays a critical role in mediating the placental glucocorticoid barrier, with its expression inhibited in IUGR cases. The epigenetic regulation mechanism of P-gp was also explored, providing new insights into early warning, prevention, and treatment strategies for IUGR.

BMC MEDICINE (2021)

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Article Engineering, Environmental

Environmental exposure to cadmium impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress

Yong-Wei Xiong et al.

Summary: Cadmium exposure can negatively affect placental angiogenesis and progesterone levels, potentially impairing fetal growth through a mechanism involving GCN-2-mediated mitochondrial stress.

JOURNAL OF HAZARDOUS MATERIALS (2021)

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Article Gastroenterology & Hepatology

Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations

Tharni Vasavan et al.

Summary: Elevated fetal and maternal serum bile acid concentrations in untreated ICP are associated with an abnormal fetal cardiac phenotype characterized by increased NT-proBNP concentration, PR interval length and HRV. UDCA treatment partially attenuates this phenotype.

JOURNAL OF HEPATOLOGY (2021)

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Article Biochemistry & Molecular Biology

The eIF2 kinase GCN2 directs keratinocyte collective cell migration during wound healing via coordination of reactive oxygen species and amino acids

Rebecca R. Miles et al.

Summary: The study demonstrates that the eIF2 kinase GCN2 plays a crucial role in maintaining intracellular amino acid balance and coordinating various cellular processes essential for wound healing, such as cell migration, ROS generation, lamellipodia formation, and focal adhesion dynamics. Inhibition or deletion of GCN2 significantly delays collective cell migration and wound closure, highlighting the importance of GCN2 in regulating the re-epithelialization of cutaneous wounds.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Article Endocrinology & Metabolism

Rhythm of Fetoplacental 11β-Hydroxysteroid Dehydrogenase Type 2-Fetal Protection From Morning Maternal Glucocorticoids

Eva Kathrin Lamade et al.

Summary: The study revealed time-specific alteration of fetoplacental 11 beta-HSD2 activity, peaking in the morning to protect fetus from maternal glucocorticoids. Acute affective or anxiety disorders were found to impact fetoplacental 11 beta-HSD2 activity.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

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Article Developmental Biology

Dexamethasone-induced intrauterine growth restriction modulates expression of placental vascular growth factors and fetal and placental growth

A. Arias et al.

Summary: Maternal dexamethasone administration during late gestation results in fetal and placental growth restriction, potentially due to altered placental angiogenesis.

MOLECULAR HUMAN REPRODUCTION (2021)

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Article Biochemistry & Molecular Biology

Melatonin protects against environmental stress-induced fetal growth restriction via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts

Hua-Long Zhu et al.

Summary: Gestational exposure to environmental stress can lead to fetal growth restriction (FGR) with reduced levels of melatonin (MT) in the placenta. MT offers protective effects against FGR by inhibiting BNIP3-dependent mitophagy, potentially serving as a therapeutic agent against environmental stress-induced developmental toxicity.

REDOX BIOLOGY (2021)

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Article Environmental Sciences

Microcystin-LR inhibits testosterone synthesis via reactive oxygen species-mediated GCN2/eIF2α pathway in mouse testes

Lan Gao et al.

Summary: The study revealed that ROS-mediated GCN2/eIF2 alpha activation plays a role in the disruption of testicular T synthesis induced by MC-LR, providing a new clue for understanding the mechanism of endocrine disruption caused by MC-LR.

SCIENCE OF THE TOTAL ENVIRONMENT (2021)

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Article Medicine, General & Internal

Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Fuzhen Song et al.

Summary: This study found that gestational hypercholanemia was associated with an increased risk of LBW and IUGR, especially in pregnant individuals with hypertensive disorders in pregnancy. Monitoring sTBA concentration during the follow-up of pregnancies with potential IUGR could be meaningful.

JAMA NETWORK OPEN (2021)

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Article Multidisciplinary Sciences

Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation

Nadine Provencal et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Multidisciplinary Sciences

Dysregulation of bile acids increases the risk for preterm birth in pregnant women

Sangmin You et al.

NATURE COMMUNICATIONS (2020)

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Article Biochemistry & Molecular Biology

Gestational vitamin D deficiency causes placental insufficiency and fetal intrauterine growth restriction partially through inducing placental inflammation

Yuan Hua Chen et al.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY (2020)

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Review Endocrinology & Metabolism

Tracking placental development in health and disease

John D. Aplin et al.

NATURE REVIEWS ENDOCRINOLOGY (2020)

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Article Environmental Sciences

Cadmium down-regulates 11 beta-HSD2 expression and elevates active glucocorticoid level via PERK/p-eIF2 alpha pathway in placental trophoblasts

Xue-Ting Shi et al.

CHEMOSPHERE (2020)

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Article Developmental Biology

The placenta in fetal growth restriction: What is going wrong?

Cherry Sun et al.

PLACENTA (2020)

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Article Multidisciplinary Sciences

Continuous association of total bile acid levels with the risk of small for gestational age infants

Li Li et al.

SCIENTIFIC REPORTS (2020)

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Review Biochemistry & Molecular Biology

Mechanisms for establishment of the placental glucocorticoid barrier, a guard for life

Ping Zhu et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2019)

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Article Pediatrics

Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery A Secondary Analysis of a Randomized Clinical Trial

Cynthia Gyamfi-Bannerman et al.

JAMA PEDIATRICS (2019)

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Article Obstetrics & Gynecology

Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study

L. B. Manna et al.

BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY (2019)

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Article Cell Biology

Obeticholic Acid Protects against Gestational Cholestasis-Induced Fetal Intrauterine Growth Restriction in Mice

Wei Chen et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2019)

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Article Obstetrics & Gynecology

From population reference to national standard: new and improved birthweight charts

Liset Hoftiezer et al.

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY (2019)

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Article Cell Biology

Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress

Ronald C. Wek

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2018)

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Article Endocrinology & Metabolism

Programming of central and peripheral insulin resistance by low birthweight and postnatal catch-up growth in male mice

Lindsey M. Berends et al.

DIABETOLOGIA (2018)

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Article Obstetrics & Gynecology

Early Second-Trimester Fetal Growth Restriction and Adverse Perinatal Outcomes

Lorene A. Temming et al.

OBSTETRICS AND GYNECOLOGY (2017)

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Article Endocrinology & Metabolism

Pregnancy Suppresses the Daily Rhythmicity of Core Body Temperature and Adipose Metabolic Gene Expression in the Mouse

Michaela D. Wharfe et al.

ENDOCRINOLOGY (2016)

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Article Immunology

Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and Intrauterine Growth Restriction through Its Anti-Inflammatory Activity

Yuan-Hua Chen et al.

JOURNAL OF IMMUNOLOGY (2016)

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Article Multidisciplinary Sciences

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

Caitlin S. Wyrwoll et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

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Article Multidisciplinary Sciences

Maternal bile acid transporter deficiency promotes neonatal demise

Yuanyuan Zhang et al.

NATURE COMMUNICATIONS (2015)

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Article Immunology

Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia

Tiziana Cotechini et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2014)

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Review Biochemistry & Molecular Biology

The eIF2α kinases: their structures and functions

Neysan Donnelly et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2013)

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Article Gastroenterology & Hepatology

Intrahepatic Cholestasis of Pregnancy and Associated Hepatobiliary Disease: A Population-Based Cohort Study

Hanns-Ulrich Marschall et al.

HEPATOLOGY (2013)

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Article Medicine, Research & Experimental

Maternal cholestasis during pregnancy programs metabolic disease in offspring

Georgia Papacleovoulou et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

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Article Biochemistry & Molecular Biology

The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression

Wafa B'chir et al.

NUCLEIC ACIDS RESEARCH (2013)

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Article Microbiology

Infection-Induced Host Translational Blockage Inhibits Immune Responses and Epithelial Renewal in the Drosophila Gut

Sveta Chakrabarti et al.

CELL HOST & MICROBE (2012)

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Article Biochemistry & Molecular Biology

Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude

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FASEB JOURNAL (2012)

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Bile acid modulates transepithelial permeability via the generation of reactive oxygen species in the Caco-2 cell line

Y Araki et al.

FREE RADICAL BIOLOGY AND MEDICINE (2005)

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Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway

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