A Shift in Glycerolipid Metabolism Defines the Follicular Fluid of IVF Patients with Unexplained Infertility

Batushansky, Albert; Zacharia, Anish; Shehadeh, Alaa; Bruck-Haimson, Reut; Saidemberg, Daniel Menezes; Kogan, Natalya M.; Mannully, Chanchal Thomas; Herzberg, Shmuel; Ben‐Meir, Assaf; Moussaieff, Arieh

doi:10.3390/biom10081135

Cited by 12 publications

(10 citation statements)

References 41 publications

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“…Although follicular glucose level didn’t show difference between the two groups of different ages, lactate level in the follicular fluid was increased in advanced age group suggesting increased anaerobic glycolysis. Lipid metabolism disorder was proved to be associated with female reproductive and endocrine functions ( 24 ). The current literature indicates that higher lipolysis and lower lipogenesis enhance the delivery of lipid metabolites ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent Metabolomic Profile of the Follicular Fluids From Women Undergoing Assisted Reproductive Technology Treatment

Huang

Qian

et al. 2022

Front. Endocrinol.

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Female fertility declines with age, and this natural variation culminates in reproductive senescence. Human follicular fluids are rich in low-molecular weight metabolites which are responsible for the maturation of oocytes. The metabolomic approaches are powerful tools to study biochemical markers of oocyte quality in the follicular fluids. It is necessary to identify and quantify the reliable metabolites in follicular fluids reflecting oocyte developmental potential. The goal of this study is to conduct a metabolomic analysis of the follicular fluids in women of different ages and study the metabolomic profile of the follicular fluids in relationship with oocyte quality in assisted reproductive technology (ART) treatment. A total of 30 women seeking for ART treatment at the Women’s Hospital, Zhejiang University School of Medicine from October 2014 to April 2015 were recruited for the present study. Fifteen women aged from 39 to 47 were grouped as advanced maternal age, and the other 15 women aged from 27 to 34, as young controls. Ovarian stimulation and oocyte retrieval were conducted using a regular protocol involving mid-luteal pituitary down-regulation and controlled ovarian stimulation. Follicular fluids from mature follicles were collected and centrifuged for analyses. Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectroscopy (GC-MS) were used to perform the quantitative metabolomic analysis. The follicular fluid levels of 311 metabolites and the metabolic significance were assessed. 70 metabolites showed significant differences between women with young and advanced ages. Follicular fluids from women with advanced age showed significantly higher levels of creatine, histidine, methionine, trans-4-hydroxyproline, choline, mevalonate, N2,N2-dimethylguanosine and gamma-glutamylvaline, as compared to those from the young age group. 8 metabolites were found significantly correlated with maternal age positively. Moreover, 3 metabolites were correlated with the number of oocytes retrieved, and 5 metabolites were correlated with cleaved embryo numbers, both negatively. The follicular fluids from women undergoing ART treatment exhibited age-dependent metabolomic profile. Metabolites associated with oocyte quality were identified, suggesting them as potential biomarkers for oocyte maturation and ART outcomes.

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Section: Discussionmentioning

confidence: 99%

Age-Dependent Metabolomic Profile of the Follicular Fluids From Women Undergoing Assisted Reproductive Technology Treatment

Huang

Qian

et al. 2022

Front. Endocrinol.

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“…A research found that mouse cumulus-oocyte complexes exposed to lipid-rich FF during their maturation had increased oocyte lipid content, induction of endoplasmic reticulum stress markers, and impaired oocyte nuclear maturation [ 17 ]. TG accumulation in the FF was also correlated to the levels of adipokines and proinflammatory cytokines in FF, implying inflammatory processes in the FF that are caused by high TG levels and may also attenuate oocyte development [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Lipidomics analysis of human follicular fluid form normal-weight patients with polycystic ovary syndrome: a pilot study

et al. 2021

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Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this pilot study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight. Methods Follicular fluid samples were collected from patients who underwent IVF, including normal-weight women without PCOS (control group, n = 10) and normal-weight women with PCOS (PCOS group, n = 8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. Results All 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC < 0.67, p-value < 0.05 and VIP value > 1. These differential species of lipid belong to lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI). Conclusion The identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal-weight.

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“…and may also attenuate oocyte development [18]. That was why PCOS patients always have the impaired oocyte development in ART.…”

Section: Discussionmentioning

confidence: 99%

“…A research found mouse cumulus-oocyte complexes (COCs) exposed to lipid-rich FF during their maturation had increased oocyte lipid content, induction of endoplasmic reticulum stress markers, and impaired oocyte nuclear maturation [17]. TG accumulation in the FF were also correlated to the levels of adipokines and proin ammatory cytokines in FF, implying in ammatory processes in the FF that are caused by high TG levels and may also attenuate oocyte development [18]. That was why PCOS patients always have the impaired oocyte development in ART.…”

Section: Discussionmentioning

confidence: 99%

Lipidomics Analysis of Human Follicular Fluid Form Normal-weight Patients With Polycystic Ovary Syndrome

Ban

Ran

Chen

et al. 2021

Preprint

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Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight.MethodsFollicular fluid samples were collected from patients who underwent IVF, including normal women (control group, n=10) and normal weight women with PCOS (PCOS group, n=8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. ResultsAll 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC<0.67, p-value <0.05 and VIP value > 1. These differential metabolites were the lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI).ConclusionThe identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal weight.

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A Shift in Glycerolipid Metabolism Defines the Follicular Fluid of IVF Patients with Unexplained Infertility

Cited by 12 publications

References 41 publications

Age-Dependent Metabolomic Profile of the Follicular Fluids From Women Undergoing Assisted Reproductive Technology Treatment

Age-Dependent Metabolomic Profile of the Follicular Fluids From Women Undergoing Assisted Reproductive Technology Treatment

Lipidomics analysis of human follicular fluid form normal-weight patients with polycystic ovary syndrome: a pilot study

Lipidomics Analysis of Human Follicular Fluid Form Normal-weight Patients With Polycystic Ovary Syndrome

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