Elevated peritoneal fluid ceramides in human endometriosis-associated infertility and their effects on mouse oocyte maturation.
Fertil Steril
; 110(4): 767-777.e5, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30196975
ABSTRACT
OBJECTIVE:
To characterize the peritoneal fluid (PF) sphingolipid profile in endometriosis-associated infertility (EAI), and to assess the plausible functional role(s) of ceramides in oocyte maturation potential.DESIGN:
Retrospective case-control study and in vitro mouse oocyte study.SETTING:
University-affiliated hospital and university laboratory.SUBJECTS:
Twenty-seven infertile patients diagnosed with endometriosis and 20 infertile patients who did not have endometriosis; BALB/c female mice. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) PF sphingolipid concentrations. Number of metaphase II (MII) mouse oocytes. RESULT(S) Liquid chromatography-tandem mass spectrometry revealed 11 significantly elevated PF sphingolipids in infertile women with severe endometriosis compared with infertile women without endometriosis (change >50%, false discovery rate ≤10%). Logistic regression analysis identified three very-long-chain ceramides potentially associated with EAI. Functional studies revealed that very-long-chain ceramides may compromise or induce murine MII oocyte maturation. The oocyte maturation effects induced by the very long-chain ceramides were triggered by alterations in mitochondrial superoxide production in a concentration-dependent manner. Scavenging of mitochondrial superoxide reversed the maturation effects of C240 ceramide. CONCLUSION(S) EAI is associated with accumulation of PF very-long-chain ceramides. Mouse studies demonstrated how ceramides affect MII oocyte maturation, mediating through mitochondrial superoxide. These results provide an opportunity for direct functional readout of pathophysiology in EAI, and future therapies targeted at this sphingolipid metabolism may be harnessed for improved oocyte maturation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oócitos
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Líquido Ascítico
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Ceramidas
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Endometriose
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Infertilidade Feminina
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article