O-GlcNAc modification mediates aquaporin 3 to coordinate endometrial cell glycolysis and affects embryo implantation

Zhang, Hongshuo; Jia, Qi; Pei, Jingyuan; Zhang, Man; Shang, Yue; Li, Zhen; Wang, Yufei; Guo, Jinqiu; Sun, Kai-qi; Fan, Jianhui; Sui, Linlin; Xu, Yan; Kong, Li; Kong, Ying

doi:10.1016/j.jare.2021.06.022

Cited by 21 publications

(12 citation statements)

References 42 publications

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“…Recently, a study showed that in addition to reduced GLUT1 in the decidua of patients with severe preeclampsia, GLUT1 deficiency may trigger aberrant glycolysis, thereby leading to poor decidualization and subsequent impaired placental development ( 52 ). Furthermore, a recent study showed that O -GlcNAcylation mediates the regulation of the water channel aquaporin 3 (AQP3) and that both elevated O -GlcNAcylation and AQP3 increase glucose uptake via GLUT1 ( 53 ). Interestingly, we have previously described that SHR presents a lack of placental AQP3 expression and that AQP3 is important for trophoblast cell migration, a crucial step during placentation ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

“…Curiously, loss of AQP3 in the placentas was shown to induce growth restriction in mice ( 55 ). O -GlcNAcylation was found to regulate GLUT1 through c-Myc ( 56 ) and AQP3 through SP1 ( 53 ). Together, our findings make a significant contribution to our understanding of how protein O -GlcNAcylation affects fetal growth and placental function during hypertension.…”

Section: Discussionmentioning

confidence: 99%

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Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy

et al. 2022

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IntroductionDuring pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension.MethodsTo investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses.ResultsSHR presented a higher blood pressure than the Wistar rats (p=0.001). Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs.ConclusionsThese findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy

et al. 2022

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“…30 Given that the precursor of the O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification, uridine diphosphate N-acetylglucosamine, connects the metabolic pathways of glucose, fatty acids, nucleic acids, and nitrogen, O-GlcNAcylation is engaged in diverse metabolic and physiological processes by rapidly and reversibly sensing a wide range of signals and affecting protein localization, interaction, activity, and degradation. 31 In their recent study, Zhang et al 32 identified an unexpected role of O-GlcNAcylation in modulating endometrial cell functions and influencing embryo implantation. O-GlcNAcylation of Glut1 increased glucose uptake and Warburg-like glycolysis during the window of implantation, and O-GlcNAcylation modification of aquaporin 3 mediated the intracellular transport of glycerol to compensate for increased glycolysis.…”

Section: Reviewmentioning

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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“…[89][90][91][92] Impaired GLUT1 expression leads to inadequate glucose uptake and dramatically reduced decidualization. 88,89,93 Von Wolff et al showed that the GLUT3 and GLUT1 expression levels were similar in different developmental stages. 89 The difference is that the expression of GLUT3 expression does not change in the stroma, gland, or CD45-positive leukocytes throughout the menstrual cycle or decidualization.…”

Section: Decidual Stromal Cellsmentioning

confidence: 99%

“…Under the control of estrogen and progesterone, GLUT1 is significantly upregulated during decidualization 89–92 . Impaired GLUT1 expression leads to inadequate glucose uptake and dramatically reduced decidualization 88,89,93 . Von Wolff et al.…”

Section: Glycolysis In Normal Pregnancymentioning

confidence: 99%

Glycolysis: A fork in the path of normal and pathological pregnancy

Gou,

Zhang

2023

The FASEB Journal

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Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal–fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal–fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal–fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.

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O-GlcNAc modification mediates aquaporin 3 to coordinate endometrial cell glycolysis and affects embryo implantation

Cited by 21 publications

References 42 publications

Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy

Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy

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

Glycolysis: A fork in the path of normal and pathological pregnancy

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