Life sciences · 2025
Impaired metabolic cooperation between oocyte and granulosa cells may contribute to the disrupted folliculogenesis and poor oocyte quality in PCOS.
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Naigaonkar Aalaap, Shinde Gayatri, Khavale Sushma, Hinduja Indira, Mukherjee Srabani
Аннотация
BACKGROUND: Oocyte quality is largely governed by metabolic cooperation between oocytes and granulosa cells (GCs). PCOS is prevalent endocrine disorder in women of reproductive age, characterized by hyperandrogenaemia, skewed gonadotropins, insulin resistance, anovulation and poor oocyte quality. We aim to unravel glucose metabolism dynamics in oocyte microenvironment in PCOS compared to healthy controls undergoing IVF using follicular fluid (FF) and GCs.
METHODS: Glucose uptake by GCs was studied. Basal GLUT4 transcript and protein expression; and its translocation were assessed in GCs by immunofluorescence. Transcript levels of genes encoding metabolic enzymes, pyruvate levels and glycation markers were assessed in follicular environment. Real-time metabolic analysis was done using Seahorse XFe24 system.
RESULTS: Basal and stimulated glucose uptake, basal GLUT4 transcript and protein expression; and translocation on insulin stimulation were significantly lower in GCs from PCOS women. In PCOS follicle, glycolysis was downregulated as indicated by decreased transcript levels of rate-limiting enzymes, reduced pyruvate levels and lower real-time glycolysis and glycolytic capacity. Alternatively, pentose phosphate pathway, polyol pathway and glycation were increased and transcript levels of gap junctional proteins were downregulated in PCOS follicle. GCs from PCOS women showed increased oxidative stress and higher expression and nuclear translocation of NRF2.
CONCLUSION: Our data indicates inherent defects in metabolism in follicular compartment in women with PCOS which may affect oocyte quality. Understanding energy dynamics in the follicle can offer valuable insights about key metabolites to be added to oocyte/embryo culture media in IVF settings and may highlight plausible markers for oocyte/embryo quality.
METHODS: Glucose uptake by GCs was studied. Basal GLUT4 transcript and protein expression; and its translocation were assessed in GCs by immunofluorescence. Transcript levels of genes encoding metabolic enzymes, pyruvate levels and glycation markers were assessed in follicular environment. Real-time metabolic analysis was done using Seahorse XFe24 system.
RESULTS: Basal and stimulated glucose uptake, basal GLUT4 transcript and protein expression; and translocation on insulin stimulation were significantly lower in GCs from PCOS women. In PCOS follicle, glycolysis was downregulated as indicated by decreased transcript levels of rate-limiting enzymes, reduced pyruvate levels and lower real-time glycolysis and glycolytic capacity. Alternatively, pentose phosphate pathway, polyol pathway and glycation were increased and transcript levels of gap junctional proteins were downregulated in PCOS follicle. GCs from PCOS women showed increased oxidative stress and higher expression and nuclear translocation of NRF2.
CONCLUSION: Our data indicates inherent defects in metabolism in follicular compartment in women with PCOS which may affect oocyte quality. Understanding energy dynamics in the follicle can offer valuable insights about key metabolites to be added to oocyte/embryo culture media in IVF settings and may highlight plausible markers for oocyte/embryo quality.