Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage

Tang, Linchen; Xu, Xianghong; Xu, Sha; Liu, Zeying; He, Qing-Yu; Li, Wenxuan; Sun, Jiaxue; Shuai, Wen; Mao, Jingwen; Zhao, Jian; Jin, Liping

doi:10.1016/j.xcrm.2023.101026

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…The process of endometrial-decidual transformation is accompanied by remarkable metabolic reprogramming. 43 Using liquid chromatography with mass spectrometry-based metabolite profiling, Tang et al 44 found that accumulated αketoglutarate derived from activated glutaminolysis contributes to decidual transformation, whereas hESCs obtained from patients with recurrent spontaneous miscarriage exhibited glutaminolysis blockade and decidual defects. Further investigation revealed that enhanced α-ketoglutarate flux decreased histone methylation and supported ATP production during decidualization.…”

Section: Recent Progress In Endometrial-decidual Transformation Resea...mentioning

confidence: 99%

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

Bao,

Wang

2024

Maternal Fetal Med

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This review aimed to summarize the major progress in maternal-fetal medicine achieved by Chinese scientists in recent years. PubMed was systematically searched from January 2020 to November 2023. Publications that reported the progress in embryo implantation, placentation, and parturition made by Chinese scientists in the last 3 years were selected. The milestone events during gestation, embryo implantation, endometrial decidualization, placentation, and parturition are pivotal to a successful pregnancy. Embryo implantation requires intricate interactions between implantation-competent blastocysts and receptive endometrium. To adapt to pregnancy, endometrial stromal cells transform into specialized decidual cells, which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in mice. With embryonic development, the placenta forms to support fetal growth until parturition. The maternal-fetal interface is composed of diverse cell types, including endometrial decidual cells, placental trophoblast cells, endothelial cells, and various immune cells, a sophisticated interplay among which contributes to the maintenance of pregnancy. Near term, the uterus transitions from quiescence to contractility, in preparation for delivery. Disruptions to these events lead to pregnancy-related disorders such as repeated implantation failure, recurrent pregnancy loss, preeclampsia, fetal growth restriction, preterm birth, and infertility. In recent years, Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy events. Chinese scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine research in recent years, highlighting future research directions in this field.

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Section: Recent Progress In Endometrial-decidual Transformation Resea...mentioning

confidence: 99%

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

Bao,

Wang

2024

Maternal Fetal Med

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“…delineated an activated glutamine (Gln) metabolism in decidualization. They uncovered the fundamental support of Gln-glutamic acid (Glu)-α-ketoglutarate (α-KG) metabolism flux for successful decidualization through Gln-Glu-αKG-dependent H3K27 demethylation in promotor regions of PRL and IGFBP1, while patients with RSA exhibited impaired decidualization owing to deficient Gln metabolism ( 75 ).…”

Section: Energy Metabolism Reprogramming In Dsc Differentiationmentioning

confidence: 99%

Energy metabolism and maternal-fetal tolerance working in decidualization

et al. 2023

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One pivotal aspect of early pregnancy is decidualization. The decidualization process includes two components: the differentiation of endometrial stromal cells to decidual stromal cells (DSCs), as well as the recruitment and education of decidual immune cells (DICs). At the maternal-fetal interface, stromal cells undergo morphological and phenotypic changes and interact with trophoblasts and DICs to provide an appropriate decidual bed and tolerogenic immune environment to maintain the survival of the semi-allogeneic fetus without causing immunological rejection. Despite classic endocrine mechanism by 17 β-estradiol and progesterone, metabolic regulations do take part in this process according to recent studies. And based on our previous research in maternal-fetal crosstalk, in this review, we elaborate mechanisms of decidualization, with a special focus on DSC profiles from aspects of metabolism and maternal-fetal tolerance to provide some new insights into endometrial decidualization in early pregnancy.

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Prenatal 1‐Nitropyrene Exposure Causes Autism‐Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain

Zhao,

Huang,

Zhang

et al. 2024

Advanced Science

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain.

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Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage

Cited by 5 publications

References 33 publications

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

Energy metabolism and maternal-fetal tolerance working in decidualization

Prenatal 1‐Nitropyrene Exposure Causes Autism‐Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain

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