Polycystic ovary syndrome(PCOS)is a complex ***-wide association studies(GWAS)have identified several genes associated with this condition,including ***1A encodes a clathrin-binding protein that functions as a guanine...
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Polycystic ovary syndrome(PCOS)is a complex ***-wide association studies(GWAS)have identified several genes associated with this condition,including ***1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular ***,the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly *** this study,we investigated DENND1A expression in ovarian granulosa cells(GCs)from PCOS patients and its correlation with *** results revealed an upregulation of DENND1A expression in GCs from PCOS cases,which was positively correlated with testosterone *** further explore the functional implications of DENND1A,we generated a transgenic mouse model overexpressing Dennd1a(TG mice).These TG mice exhibited subfertility,irregular estrous cycles,and increased testosterone production following PMSG ***,the TG mice displayed diminished responsiveness to FSH,characterized by smaller ovary size,less well-developed follicles,and abnormal expressions of FSH-priming ***,we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor(FSHR),promoting its internalization and inhibiting *** findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms,thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.
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