Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
|---|---|
| Enthalten in: |
Scientific reports - 6(2016) vom: 13. Jan., Seite 19436 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jia, Longfei [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
7440-44-0 |
|---|
| Anmerkungen: |
Date Completed 13.12.2016 Date Revised 13.11.2018 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/srep19436 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM25637564X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM25637564X | ||
| 003 | DE-627 | ||
| 005 | 20231226192502.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/srep19436 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0854.xml |
| 035 | |a (DE-627)NLM25637564X | ||
| 035 | |a (NLM)26758245 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jia, Longfei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.12.2016 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a DNA, Mitochondrial |2 NLM | |
| 650 | 7 | |a Repressor Proteins |2 NLM | |
| 650 | 7 | |a Carbon |2 NLM | |
| 650 | 7 | |a 7440-44-0 |2 NLM | |
| 700 | 1 | |a Li, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Yingjie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chenfei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ruqian |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 6(2016) vom: 13. Jan., Seite 19436 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
| 773 | 1 | 8 | |g volume:6 |g year:2016 |g day:13 |g month:01 |g pages:19436 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/srep19436 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 6 |j 2016 |b 13 |c 01 |h 19436 | ||