title: Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries.
abstract: Polycystic ovarian syndrome (PCOS) is associated with hyperhomocysteinemia and polycystic ovaries (PCO) usually produce oocytes of poor quality. However, the intracellular mechanism linking hyperhomocysteinemia and oocyte quality remains elusive. In this study, the quality of the oocytes isolated from healthy and polycystic gilt ovaries was evaluated in vitro in association with one-carbon metabolism, mitochondrial DNA (mtDNA) methylation, and mitochondrial function. PCO oocytes demonstrated impaired polar body extrusion, and significantly decreased cleavage and blastocyst rates. The mitochondrial distribution was disrupted in PCO oocytes, together with decreased mitochondrial membrane potential and deformed mitochondrial structure. The mtDNA copy number and the expression of mtDNA-encoded genes were significantly lower in PCO oocytes. Homocysteine concentration in follicular fluid was significantly higher in PCO group, which was associated with significantly up-regulated one-carbon metabolic enzymes betaine homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT) and the DNA methyltransferase DNMT1. Moreover, mtDNA sequences coding for 12S, 16S rRNA and ND4, as well as the D-loop region were significantly hypermethylated in PCO oocytes. These results indicate that an abnormal activation of one-carbon metabolism and hypermethylation of mtDNA may contribute, largely, to the mitochondrial malfunction and decreased quality of PCO-derived oocytes in gilts.
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P. R. China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P. R. China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, P. R. China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Niu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, P. R. China.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P. R. China.|Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing 210095, P. R. China.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism*; D019175:DNA Methylation; D004272:DNA, Mitochondrial; D005260:Female; D005399:Fishes; D018628:Gene Dosage; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D053078:Membrane Potential, Mitochondrial; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D009865:Oocytes / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D012097:Repressor Proteins; D002244:Carbon