title: Elevated non-esterified fatty acid concentrations during in vitro murine follicle growth alter follicular physiology and reduce oocyte developmental competence.
abstract: OBJECTIVE
  To study how long-term elevated non-esterified fatty acid (NEFA) concentrations, typical in metabolic disorders such as obesity or type 2 diabetes, affect murine follicular development, follicle quality, and subsequent oocyte developmental competence in vitro.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  In vitro culture setting.
  
  
  METHODS
  Female and male 13-day old, B6CBAF1 mice of proven fertility were sacrificed for harvesting ovaries and epididymal sperm, respectively.
  
  
  METHODS
  Early secondary murine follicles were cultured in vitro in the presence of NEFAs until the antral stage (12 days). Treatments consisted of one or a mixture of NEFAs (stearic acid [SA], palmitic acid [PA], oleic acid [OA]) in physiological (basal) or pathological (high SA, high OA, high NEFA) concentrations.
  
  
  METHODS
  Follicular development; follicle and oocyte diameters; secretion of progesterone, estradiol, and inhibin B; and luteinized granulosa cell gene expression patterns were investigated. Oocytes from NEFA-exposed follicles were fertilized in vitro, and presumptive zygotes were cultured until the blastocyst stage.
  
  
  RESULTS
  Exposure to high SA reduced follicle diameters and day-12 antrum formation. Elevated NEFA concentrations changed luteinized granulosa cell messenger-ribonucleic acid abundance of genes related to energy/fatty acid/steroid metabolism, apoptosis, and oxidative stress. High NEFA and high SA treatments increased progesterone synthesis, compared with high OA follicles. Oocyte developmental competence was substantially reduced in oocytes retrieved from high OA-, high SA-, and high NEFA-exposed follicles compared with basal-treated follicles.
  
  
  CONCLUSIONS
  This study showed, for the first time, that lipolysis-linked, elevated NEFA concentrations can potentially impair fertility, by altering follicular physiology and reducing oocyte developmental competence.
authors.affiliation: Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium. Electronic address: sara.valckx@uantwerpen.be.
authors.forename: Sara D M
authors.initials: SD
authors.lastname: Valckx
authors.affiliation: Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Hoeck
authors.affiliation: Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Arias-Alvarez
authors.affiliation: Department of Animal Reproduction, National Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Maillo
authors.affiliation: Department of Animal Reproduction, National Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain; Biogénesis, University of Antioquia, Antioquia, Colombia.
authors.forename: Angela P
authors.initials: AP
authors.lastname: Lopez-Cardona
authors.affiliation: Department of Animal Reproduction, National Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gutierrez-Adan
authors.affiliation: Algemeen Medisch Laboratorium, Antwerp, Belgium.
authors.forename: Mario
authors.initials: M
authors.lastname: Berth
authors.affiliation: EggCentris Besloten Vennootschap met Beperkte Aansprakelijkheid, Evergem, Belgium.
authors.forename: Rita
authors.initials: R
authors.lastname: Cortvrindt
authors.affiliation: Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Peter E J
authors.initials: PE
authors.lastname: Bols
authors.affiliation: Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Jo L M R
authors.initials: JL
authors.lastname: Leroy
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D007265:Inhibins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology*; D010060:Ovulation; D011374:Progesterone / Q000096:biosynthesis
chemical_list: D005230:Fatty Acids, Nonesterified; C422364:inhibin B; D011374:Progesterone; D007265:Inhibins
keywords: Metabolic disorder; NEFA; folliculogenesis; obesity; oocyte developmental competence