Direct impact of gonadotropins on glucose uptake and storage in preovulatory granulosa cells: Implications in the pathogenesis of polycystic ovary syndrome

Chahal, Nidhi; Geethadevi, Anjali; Kaur, Surleen; Lakra, Ruchi; Nagendra, A; Shrivastav, Tulsidas G.; Pascali, Francesco De; Reiter, Eric; Crépieux, Pascale; Devi, M. Gouri; Malhotra, Neena; Muralidhar, K.; Singh, Rita

doi:10.1016/j.metabol.2020.154458

Cited by 18 publications

(16 citation statements)

References 81 publications

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“…Our study found lower circulating glycine in patients with FOI < 1, which would result in a poor response to ovarian stimulation via glucose metabolism pathway. This founding was in accordance with the study of Chahal, et al [24].…”

Section: Discussionsupporting

confidence: 94%

Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Pei

Zhu

et al. 2022

Horm Metab Res

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In in vitro fertilization (IVF), it is meaningful to find novel biomarkers predicting ovarian response in advance. To identify serum metabolomics predicting ovarian response after controlled ovarian stimulation (COS). Blood samples collected at the start of pituitary downregulation and on the fifth day after COS using Liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods were analyzed to quantify metabolites. Demographic data were calculated with SPSS version 22.0 software. Multivariate statistics were used to analyze metabolomics dataset. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic model. Analyses revealed 50 different metabolomics between the pre- and post-COS groups. Compared with baseline, amino acids increased significantly following COS. At baseline, acetylglycine was more abundant in FOI <1 group, while glycine and lipids increased in FOI ≥1 group. After COS, glycine, N-acetyl-L-alanine, D-alanine, and 2-aminomuconic acid were higher in those with FOI ≥1, but L-glutamine was abundant in FOI <1. ROC curves indicated that combination of glycine, acetylglycine and lipids predicts different responses to COS (AUC =0.866). Serum metabolism might reflect the response to ovarian stimulation. Higher glycine and PC may be a good predictor for response to COS.

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Section: Discussionsupporting

confidence: 94%

Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Pei

Zhu

et al. 2022

Horm Metab Res

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show abstract

Section: Discussionsupporting

confidence: 94%

Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Pei

Zhu

et al. 2021

Preprint

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Introduction In in vitro fertilization (IVF) cycles, some patients fail to adequately respond to ovarian stimulation. Finding novel biomarkers predicting ovarian response in advance would be meaningful.Objective To identify serum metabolomics predicting the growth of follicles after controlled ovarian stimulation (COS).Methods Blood samples were collected at the start of pituitary downregulation and on the fifth day after controlled ovarian stimulation. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods were used to quantify metabolites. Demographic data were calculated with SPSS version 22.0 software. Multivariate statistics were used to analyze metabolomics dataset. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic model.Results The number of retrieved oocytes was higher in the group of Follicle-to-oocyte index (FOI) ≥ 1 group. Analyses revealed 50 different metabolomics between the pre- and post- COS groups. Compared with baseline, amino acids increased significantly following COS. At baseline, acetylglycine was more abundant in the FOI <1 group, while glycine and lipids were more abundant in the FOI ≥1 group. After COS, glycine, N-acetyl-L-alanine, D-alanine, and 2-aminomuconic acid were increased in those with FOI ≥1, but L-glutamine was increased in those with FOI <1. ROC curves indicated that the combination of glycine, acetylglycine and lipids predicts different responses to controlled ovarian stimulation (AUC =0.866).Conclusion Serum metabolism might reflect the response to ovarian stimulation. Higher glycine and PC may be a good predictor for response to COS.

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“…Glucose uptake and metabolism in GCs supply essential energy substrates and intermediates to ensure oocyte maturation, and disturbance of the metabolic function of GCs leads to abnormalities in follicle development [ 41 , 42 , 43 ]. Glucose is metabolized through the glycolytic pathway, pentose phosphate pathway (PPP), HBP, and polyol pathway [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine

Wang

Feng

Sun

et al. 2022

IJMS

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O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.

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Direct impact of gonadotropins on glucose uptake and storage in preovulatory granulosa cells: Implications in the pathogenesis of polycystic ovary syndrome

Cited by 18 publications

References 81 publications

Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine

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