Regulation of uterus and placenta remodeling under high estradiol levels in gestational diabetes mellitus models

Kang, Da; Kim, Min Jae; Mohamed, El-Sayed; Kim, Dasom; Jeong, Jea Sic; Kim, So Young; Kang, Hyun-Mi; Lee, Geun‐Shik; Hong, Eui-Ju; Ahn, Changhwan; Jung, Eui-Man; An, Beum‐Soo; Kim, Seung‐Chul

doi:10.1093/biolre/ioad059

Cited by 3 publications

(1 citation statement)

References 62 publications

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“…In T1DM patients, estradiol levels are higher compared to the control group [ 37 ]. Moreover, based on the vivo experimental model, researchers from Korea found that the placenta and uterus were rebuilt in the rats with GDM, resulting in the upregulation of genes related to estradiol production [ 38 ]. This suggests that the estradiol may be a potential mediator between endometriosis and diabetes.…”

Section: Discussionmentioning

confidence: 99%

Causal effects of glycemic traits and endometriosis: a bidirectional and multivariate mendelian randomization study

Xin,

Li,

Chen

et al. 2024

Diabetol Metab Syndr

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Background Observational studies have suggested an association between endometriosis and glycemic traits, but causality remains unclear. We used bidirectional and multivariate Mendelian randomization (MR) to examine the causal effect of glycemic traits on endometriosis and vice versa. Methods We obtained genome-wide association studies summary data of endometriosis and glycemic traits in our study. Inverse variance weighted (IVW), Weighted median, MR-Egger and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were applied in bidirectional two-sample MR analyses. MVMR was implemented to estimate the causal effect for fasting insulin (FI), fasting glucose (FG), and glycosylated hemoglobin A1c (HbA1c) on endometriosis. To test the validity of our findings, a number of sensitivity analyses were conducted. Results The risk of endometriosis was significantly increased by genetically predicted T1DM (OR = 1.02, 95% CI 1.00-1.04, p = 0.0171, q = 0.0556) and GDM (OR = 1.01, 95% CI 1.01–1.02, p = 1.34 × 10− 8, q = 1.74 × 10− 7). Endometriosis had a suggestive association with HbA1c (Beta = 0.04, 95% CI 0.00-0.08, p = 0.0481, q = 0.1251). Using multivariate Mendelian randomization (MVMR), a significant causal effect of FI on genetically predicted endometriosis was found (OR = 2.18, 95% CI 1.16–4.09, p = 0.0154, q = 0.0547). Moreover, no causal associations between endometriosis and other glycemic traits were detected. Conclusion Our findings supported the significant causal associations of T1DM, GDM and FI with endometriosis, respectively. Additionally, a suggestive association was found of endometriosis on HbA1c. Importantly, our study may shed light on etiology studies and clinical management of endometriosis.

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Section: Discussionmentioning

confidence: 99%

Causal effects of glycemic traits and endometriosis: a bidirectional and multivariate mendelian randomization study

Xin,

Li,

Chen

et al. 2024

Diabetol Metab Syndr

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Visfatin (NAMPT) expression in human placenta cells in normal and pathological conditions and its hormonal regulation in trophoblast JEG-3 cells

Dawid,

Kurowska,

Pawlicki

et al. 2024

PLoS ONE

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Visfatin is an adipokine involved in energy metabolism, insulin resistance, inflammation, and female reproduction. Due to limited data about its action in the human placenta, the aims of our studies included the analysis of visfatin expression and immunolocalization in trophoblast cell lines JEG-3 and BeWo as well as in human placentas from normal and pathological pregnancies. Moreover, we also checked the hormonal regulation of visfatin levels and the molecular mechanism of observed changes in JEG-3 cells. Cell culture and placental fragments collection along with statistical analysis were performed using standard laboratory procedures also described in our previous papers. We demonstrated an increased gene and protein expression of visfatin in JEG-3, BeWo cells, while variable expression in maternal and fetal parts of normal/ pathological pregnancy placentas. In addition, the immunolocalization of visfatin was observed in the cytoplasm of both cell lines, the capillary epithelium of the maternal part and syncytiotrophoblasts of the placental fetal part; in all tested pathologies, the signal was also detected in decidual cells. Furthermore, we demonstrated that hormones: progesterone, estradiol, human chorionic gonadotropin, and insulin increased the visfatin levels in JEG-3 cells with the involvement of specific signaling pathways. Taken together, differences in the expression and localization of visfatin between normal and pathological placentas suggested that visfatin may be a potential marker for the diagnosis of pregnancy disorders. In addition, we found that placental levels of visfatin can be regulated by hormones known to modulate the function of placental cells.

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Unravelling the Crosstalk between Estrogen Deficiency and Gut-biota Dysbiosis in the Development of Diabetes Mellitus

Rishabh,

Bansal,

Goel

et al. 2024

CDR

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Estrogens are classically considered essential hormonal signals, but they exert profound effects in a number of physiological and pathological states, including glucose homeostasis and insulin resistance. Estrogen deficiency after menopause in most women leads to increased androgenicity and changes in body composition, and it is recommended to manipulate the β-cell function of the pancreas, insulin-induced glucose transport, and hepatic glucose output, hence, the increasing incidence of type 2 diabetes mellitus. Recently, studies have reported that gut biota alteration due to estrogen deficiency contributes to altered energy metabolism and, hence, accentuates the pathology of diabetes mellitus. Emerging research suggests estrogen deficiency via genetic disposition or failure of ovaries to function in old age modulates the insulin resistance and glucose secretion workload on pancreatic beta cells by decreasing the levels of good bacteria such as Akkermansia muciniphila, Bifidobacterium spp., Lactobacillus spp., Faecalibacterium prausnitzii, Roseburia spp., and Prevotella spp., and increasing the levels of bad bacteria’s such as Bacteroides spp., Clostridium difficile, Escherichia coli, and Enterococcus spp. Alteration in these bacteria's concentrations in the gut further leads to the development of impaired glucose uptake by the muscles, increased gluconeogenesis in the liver, and increased lipolysis and inflammation in the adipose tissues. Thus, the present review paper aims to clarify the intricate interactions between estrogen deficiency, gut microbiota regulation, and the development of diabetes mellitus.

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Regulation of uterus and placenta remodeling under high estradiol levels in gestational diabetes mellitus models

Cited by 3 publications

References 62 publications

Causal effects of glycemic traits and endometriosis: a bidirectional and multivariate mendelian randomization study

Causal effects of glycemic traits and endometriosis: a bidirectional and multivariate mendelian randomization study

Visfatin (NAMPT) expression in human placenta cells in normal and pathological conditions and its hormonal regulation in trophoblast JEG-3 cells

Unravelling the Crosstalk between Estrogen Deficiency and Gut-biota Dysbiosis in the Development of Diabetes Mellitus

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