title: Exposure to lipid-rich follicular fluid is associated with endoplasmic reticulum stress and impaired oocyte maturation in cumulus-oocyte complexes.
abstract: OBJECTIVE
  To determine whether the high lipid content of human follicular fluid influences oocyte maturation.
  
  
  METHODS
  Mouse oocytes as substitutes for human oocytes were exposed to follicular fluids of differing lipid content with outcome monitoring.
  
  
  METHODS
  Private infertility clinic and university laboratory.
  
  
  METHODS
  Seventy-four women seeking assisted reproduction, and gonadotropin-stimulated mice.
  
  
  METHODS
  Assay of follicular fluids for triglyceride and free fatty acids, and stimulation of mouse cumulus-oocyte complexes (COCs) to maturity in vitro in the presence of lipid-rich or lipid-poor follicular fluid.
  
  
  METHODS
  Oocyte lipid content, expression of endoplasmic reticulum stress marker genes, and oocyte maturation assessed in mouse COCs exposed to lipid-rich follicular fluid were compared with complexes exposed to lipid-poor follicular fluid and complexes matured in vivo.
  
  
  RESULTS
  Follicular fluids were obtained from women of known body mass index undergoing oocyte aspiration at a private infertility clinic, and the follicular fluids were assayed for triglyceride and free fatty acids; those with the highest and lowest levels of these lipids were selected. The mouse COCs exposed to lipid-rich follicular fluid during their maturation had increased oocyte lipid content, induction of endoplasmic reticulum stress markers, and impaired oocyte nuclear maturation.
  
  
  CONCLUSIONS
  Increased body mass index is associated with elevated triglycerides and free fatty acids in ovarian follicular fluid. Maturation within this lipid-rich environment is detrimental to oocytes.
authors.affiliation: Reproductive Medical Center, Sixth Affiliated Hospital of Sun Yan-sen University, Guangzhou, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.forename: Linda L
authors.initials: LL
authors.lastname: Wu
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Chura
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
authors.forename: Michelle
authors.initials: M
authors.lastname: Lane
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Norman
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Robker
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics; D051702:Activating Transcription Factor 6 / Q000235:genetics; D000818:Animals; D015992:Body Mass Index; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D054885:Cumulus Cells / Q000166:cytology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism* / Q000503:physiopathology; D007247:Infertility, Female / Q000628:therapy; D008055:Lipids / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009865:Oocytes / Q000166:cytology*; D000070780:Perilipin-2
chemical_list: D051702:Activating Transcription Factor 6; C081452:Atf4 protein, mouse; C497112:Atf6 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008055:Lipids; D008565:Membrane Proteins; D000070780:Perilipin-2; D051701:Activating Transcription Factor 4