Metabolic profile of women with premature ovarian insufficiency compared with that of age-matched healthy controls

Huang, Yizhou; Lv, Yifei; Qi, Tongyun; Luo, Zhou; Meng, Xingjun; Ying, Qian; Li, Die; Li, Chunming; Lan, Yibing; Chu, Ketan; Fu, Dongxia; Chen, Peiqiong; Xu, Wenxian; Jia, Yingxian; Li, Saisai; Cen, Xiaoping; Li, Li; Xu, Ling; Ma, Linjuan; Zhou, Jianhong

doi:10.1016/j.maturitas.2021.04.003

Cited by 13 publications

(10 citation statements)

References 33 publications

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“…Another cross-sectional casecontrol study points out women with POI were more likely to exhibit increased serum levels of TG (β, 0.155; 95% CI, 0.086, 0. (Huang et al, 2021). In conclusion, a higher risk of metabolic syndrome was associated with POI.…”

Section: Discussionmentioning

confidence: 71%

“…These association studies pointed out that serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the POI group compared with a healthy matched control group ( Ates et al, 2014 ; Podfigurna et al, 2018 ). Another cross-sectional case-control study points out women with POI were more likely to exhibit increased serum levels of TG (β, 0.155; 95% CI, 0.086, 0.223) and glucose (0.067; 0.052, 0.083), decreased levels of HDL-C (−0.087; −0.123, −0.051), LDL-C (−0.047; −0.091, −0.003) and uric acid (−0.053; −0.090, −0.015), and impaired kidney function (urea [0.070; 0.033, 0.107]; creatinine [0.277; 0.256, 0.299]; and eGFR [−0.234; −0.252, −0.216]) compared with controls after adjusting for age and BMI ( Huang et al, 2021 ). In conclusion, a higher risk of metabolic syndrome was associated with POI.…”

Section: Discussionmentioning

confidence: 99%

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Construction of a ceRNA-based lncRNA–mRNA network to identify functional lncRNAs in premature ovarian insufficiency

Luo

Zhang

et al. 2022

Front. Genet.

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Premature ovarian insufficiency, characterized by ovarian infertility and low fertility, has become a significant problem in developed countries due to its propensity for late delivery. It has been described that the vital role of lncRNA in the development and progression of POI. The aim of this work was to create a POI-based lncRNA–mRNA network (POILMN) to recognize key lncRNAs. Overall, differently expressed mRNAs (DEGs) and differently expressed lncRNAs (DELs) were achieved by using the AnnoProbe and limma R packages. POI-based lncRNA–mRNA network (POILMN) construction was carried out using the tinyarray R package and hypergeometric distribution. To identify key lncRNAs, we used CentiScaPe plug-in Cytoscape as a screening tool. In total, 244 differentially expressed lncRNAs (DELs) and 288 differentially expressed mRNAs (DEGs) were obtained in this study. Also, 177 lncRNA/mRNA pairs (including 39 lncRNAs and 86 mRNAs) were selected using the hypergeometric test. Finally, we identified four lncRNA (HCP5, NUTM2A-AS1, GABPB1-IT1, and SMIM25) intersections by topological analysis between two centralities (degree and betweenness), and we explored their subnetwork GO and KEGG pathway enrichment analysis. Here, we have provided strong evidence for a relationship with apoptosis, DNA repair damage, and energy metabolism terms and pathways in the key lncRNAs in our POI-based lncRNA–mRNA network. In addition, we evaluated the localization information of genes related to POI and found that genes were more distributed on chromosomes 15, 16, 17, and 19. However, more experiments are needed to confirm the functional significance of such predicted lncRNA/mRNA. In conclusion, our study identified four long non-coding RNA molecules that may be relevant to the progress of premature ovarian insufficiency.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Construction of a ceRNA-based lncRNA–mRNA network to identify functional lncRNAs in premature ovarian insufficiency

Luo

Zhang

et al. 2022

Front. Genet.

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“…Several clinical lines of evidence support our findings. For example, women with POI exhibit abnormalities of lipid metabolism and metabolic profiles 54 , 55 . Dysregulation of follicle fatty acids is a potential driver of human POI, as free fatty acid treatment reduces the proliferation rate and induces obvious apoptosis signals in granulosa cells isolated from the ovaries 56 .…”

Section: Discussionmentioning

confidence: 99%

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

Wang

Liu

et al. 2022

Nat Commun

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Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, severe daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We previously identified a Basonuclin 1 (BNC1) mutation from a large Chinese POI pedigree and found that mice with targeted Bnc1 mutation exhibit symptoms of POI. In this study, we found that BNC1 plays key roles in ovarian reserve and maintaining lipid metabolism and redox homeostasis in oocytes during follicle development. Deficiency of BNC1 results in premature follicular activation and excessive follicular atresia. Mechanistically, BNC1 deficiency triggers oocyte ferroptosis via the NF2-YAP pathway. We demonstrated that pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced POI. These findings uncover a pathologic mechanism of POI based on BNC1 deficiency and suggest YAP and ferroptosis inhibitors as potential therapeutic targets for POI.

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“…The alteration of lipid metabolites in POI with respect to Eggerthella is unclear. Nevertheless, abnormalities in lipid metabolism and glucose metabolism and a reduction in kidney function have been reported in females with POI ( 31 , 32 ). As mentioned earlier, an association between POI and increased risk of T2DM has also been recognized ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency

et al. 2021

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ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman’s rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

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Metabolic profile of women with premature ovarian insufficiency compared with that of age-matched healthy controls

Cited by 13 publications

References 33 publications

Construction of a ceRNA-based lncRNA–mRNA network to identify functional lncRNAs in premature ovarian insufficiency

Construction of a ceRNA-based lncRNA–mRNA network to identify functional lncRNAs in premature ovarian insufficiency

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency

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