Metabolic characteristics and pathogenesis of precocious puberty in girls: the role of perfluorinated compounds

BMC Medicine

Research Article

Rong Huang¹  Yanyan Lin¹  Jing Chen¹  Yajie Chang²  Jinxia Wu²  Jianghua Feng²  Guiping Shen²  Hongwei Zhu³  Lin Che⁴ 

[1] Department of Child Health, Women and Children’s Hospital, School of Medicine, Xiamen University, 361003, Xiamen, Fujian, China;Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Siming District, 422 Siming South Road, 361005, Xiamen, Fujian, China;Department of Pediatrics, The First Affiliated Hospital of Bengbu Medical College, 233000, Anhui, Bengbu, China;Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, 510060, Guangzhou, Guangdong, China;

关键词: Premature thelarche;    Central precocious puberty;    Specific biomarkers;    Metabolic network;    Perfluorinated compounds;   

DOI  :  10.1186/s12916-023-03032-0

 received in 2023-02-19, accepted in 2023-08-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPrecocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP.MethodsNuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP.ResultsThe disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT.ConclusionsThe elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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