Early human development · 2026
Metabolomic insights into potential early neurodevelopment in offspring of women with polycystic ovary syndrome: Maternal and fetal serum metabolomics based on a prospective birth cohort study.
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Cao Qi, Zhu Huili, Zhou Rong, Huang Wei
Аннотация
OBJECTIVE: This study aimed to characterize maternal-fetal serum metabolomics profiles in polycystic ovary syndrome (PCOS) pregnancies and explore potential links between metabolomic alterations and neurodevelopmental outcomes in offspring.
METHODS: A prospective birth cohort study enrolled 20 PCOS and 20 non-PCOS women (selected via propensity score matching from a larger cohort of 58 non-PCOS participants) from West China Second University Hospital, Sichuan University, between January 2019 and January 2020. Offspring development was assessed at 27 months using the Ages & Stages Questionnaires (ASQ). Non-targeted metabolomics analyses were performed on maternal serum (collected at 32-36 weeks of gestation) and fetal serum from the umbilical vein at delivery. Metabolite pattern recognition was performed using supervised OPLS-DA and genetic algorithms (GA) to identify significant metabolites, with pathway enrichment analysis conducted using the KEGG database.
RESULTS: Women with PCOS exhibited significantly higher testosterone and free androgen index levels across pregnancy. Metabolomics analysis identified 32 differentially abundant metabolites in maternal serum, mainly related to unsaturated fatty acid and histidine metabolism, and 28 metabolites in fetal serum, including those involved in pyrimidine metabolism. Enrichment analyses revealed schizophrenia-related pathways in both PCOS maternal and fetal serum-a finding mechanistically relevant to neurodevelopmental risks in PCOS offspring. Notably, these metabolomic changes were enriched in placental pathways and involved the retinoic acid-related orphan receptor alpha (RORA), which may contribute to neurodevelopmental abnormalities observed in offspring of PCOS patients.
CONCLUSION: This study identifies a potential link between maternal metabolic disturbances in PCOS and neurodevelopmental abnormalities in offspring through metabolomic analysis. Significant metabolites related to unsaturated fatty acids, pyrimidine, and histidine metabolism were found, with pathways enriched in neurodevelopmental disorders, particularly involving the RORA.
METHODS: A prospective birth cohort study enrolled 20 PCOS and 20 non-PCOS women (selected via propensity score matching from a larger cohort of 58 non-PCOS participants) from West China Second University Hospital, Sichuan University, between January 2019 and January 2020. Offspring development was assessed at 27 months using the Ages & Stages Questionnaires (ASQ). Non-targeted metabolomics analyses were performed on maternal serum (collected at 32-36 weeks of gestation) and fetal serum from the umbilical vein at delivery. Metabolite pattern recognition was performed using supervised OPLS-DA and genetic algorithms (GA) to identify significant metabolites, with pathway enrichment analysis conducted using the KEGG database.
RESULTS: Women with PCOS exhibited significantly higher testosterone and free androgen index levels across pregnancy. Metabolomics analysis identified 32 differentially abundant metabolites in maternal serum, mainly related to unsaturated fatty acid and histidine metabolism, and 28 metabolites in fetal serum, including those involved in pyrimidine metabolism. Enrichment analyses revealed schizophrenia-related pathways in both PCOS maternal and fetal serum-a finding mechanistically relevant to neurodevelopmental risks in PCOS offspring. Notably, these metabolomic changes were enriched in placental pathways and involved the retinoic acid-related orphan receptor alpha (RORA), which may contribute to neurodevelopmental abnormalities observed in offspring of PCOS patients.
CONCLUSION: This study identifies a potential link between maternal metabolic disturbances in PCOS and neurodevelopmental abnormalities in offspring through metabolomic analysis. Significant metabolites related to unsaturated fatty acids, pyrimidine, and histidine metabolism were found, with pathways enriched in neurodevelopmental disorders, particularly involving the RORA.