Multi‐miRNAs‐Mediated Hepatic Lepr Axis Suppression: A Pparg–Dicer1 Pathway‐Driven Mechanism in Spermatogenesis for the Intergenerational Transmission of Paternal Metabolic Syndrome DOI Creative Commons
Yi Lin, Xiuye Ni, Lin Zhu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Bisphenol A (BPA) is an “environmental obesogen” and this study aims to investigate the intergenerational impacts of BPA‐induced metabolic syndrome (MetS), specifically focusing on unraveling mechanisms. Exposure BPA induces disorders in paternal mice, which are then transmitted offspring, leading late‐onset MetS. Mechanistically, upregulates Srebf1, turn promotes Pparg‐dependent transcription Dicer1 spermatocytes, increasing levels multiple sperm microRNAs (miRNAs). Several these miRNAs highly expressed a synchronized manner liver offspring. miR149‐5p, miR150‐5p, miR700‐5p target specific region Lepr 3′UTR, termed “SMITE” (“ S everal Mi RNAs T argeting E lements”), negatively regulate Lepr. These i nherited nti‐ L epr miRNAs, also referred (IAL‐miRs), modulate hepatic steatosis, insulin signaling through regulatory Igfbp2, Egfr, Ampk. Furthermore, IAL‐miRs inhibit Ccnd1 not only via binding but Lepr–Igfbp2 axis, contribute hepatocyte senescence. pathological processes interact self‐reinforcing cycle, worsening MetS BPA‐exposed The findings reveal mechanism wherein lipid metabolism reprogramming spermatocytes‐induced perturbations triggered by BPA, leads inheritance suppression axis

Language: Английский

Multi‐miRNAs‐Mediated Hepatic Lepr Axis Suppression: A Pparg–Dicer1 Pathway‐Driven Mechanism in Spermatogenesis for the Intergenerational Transmission of Paternal Metabolic Syndrome DOI Creative Commons
Yi Lin, Xiuye Ni, Lin Zhu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Bisphenol A (BPA) is an “environmental obesogen” and this study aims to investigate the intergenerational impacts of BPA‐induced metabolic syndrome (MetS), specifically focusing on unraveling mechanisms. Exposure BPA induces disorders in paternal mice, which are then transmitted offspring, leading late‐onset MetS. Mechanistically, upregulates Srebf1, turn promotes Pparg‐dependent transcription Dicer1 spermatocytes, increasing levels multiple sperm microRNAs (miRNAs). Several these miRNAs highly expressed a synchronized manner liver offspring. miR149‐5p, miR150‐5p, miR700‐5p target specific region Lepr 3′UTR, termed “SMITE” (“ S everal Mi RNAs T argeting E lements”), negatively regulate Lepr. These i nherited nti‐ L epr miRNAs, also referred (IAL‐miRs), modulate hepatic steatosis, insulin signaling through regulatory Igfbp2, Egfr, Ampk. Furthermore, IAL‐miRs inhibit Ccnd1 not only via binding but Lepr–Igfbp2 axis, contribute hepatocyte senescence. pathological processes interact self‐reinforcing cycle, worsening MetS BPA‐exposed The findings reveal mechanism wherein lipid metabolism reprogramming spermatocytes‐induced perturbations triggered by BPA, leads inheritance suppression axis

Language: Английский

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