title: Blood cell mitochondrial DNA content and premature ovarian aging.
abstract: Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.
authors.affiliation: Laboratori di Ricerche Endocrino-Metaboliche e, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bonomi
authors.forename: Edgardo
authors.initials: E
authors.lastname: Somigliana
authors.forename: Chiara
authors.initials: C
authors.lastname: Cacciatore
authors.forename: Marta
authors.initials: M
authors.lastname: Busnelli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rossetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonetti
authors.forename: Alessio
authors.initials: A
authors.lastname: Paffoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.forename: Guido
authors.initials: G
authors.lastname: Ragni
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
mesh_terms: D000293:Adolescent; D000328:Adult; D001773:Blood Cells / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016649:Primary Ovarian Insufficiency / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial