title: Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes.
abstract: BACKGROUND
  Follicular fluid (FF) is an important micro-environment influencing oocyte growth, its development competence, and embryo viability. The FF content analysis allows to identify new relevant biomarkers, which could be predictive of in vitro fertilization (IVF) outcomes. Inside ovarian follicle, the amount of FF components from granulosa cells (GC) secretion, could be regulated by gonadotropins, which play a major role in follicle development.
  
  
  METHODS
  This prospective study included 61 female undergoing IVF or Intra-cytoplasmic sperm injection (ICSI) procedure. Apolipoprotein B (APOB) concentrations in follicular fluid and APOB gene and protein expression in granulosa cells from reproductively aged women undergoing an in vitro fertilization program were measured. The statistical analyses were performed according to a quartile model based on the amount of APOB level found in FF.
  
  
  RESULTS
  Amounts of APOB were detected in human FF samples (mean ± SD: 244.6 ± 185.9 ng/ml). The odds of obtaining an oocyte in the follicle and a fertilized oocyte increased significantly when APOB level in FF was higher than 112 ng/ml [i.e., including in Quartile Q 2, Q3 and Q4] (p = 0.001; p < 0.001, respectively). The probabilities of obtaining an embryo and a top quality embryo on day 2, were significantly higher if APOB levels were within the ranges of 112 and 330 ng/ml (i.e. in Q2 and Q3) or 112 and 230 ng/ml (i.e. in Q2), respectively (p < 0.001; p = 0.047, respectively). In addition, our experiments in vitro indicated that APOB gene and protein expression, along with APOB content into culture were significantly under-expressed in GC upon stimulation with gonadotropins (follicular stimulating hormone: FSH and/or human chorionic gonadotropin: hCG).
  
  
  CONCLUSIONS
  We are reporting a positive and statistically significant associations between APOB and oocyte retrieval, oocyte fertilization, and embryo quality. Using an experimental study component, the authors report significant reduced APOB expression and content for luteinized granulosa cells cultured in the presence of gonadotropins.
authors.affiliation: ART-PGD Department, INSERM U1203, Arnaud de Villeneuve Hospital, CHU Montpellier, Montpellier, France. elodie.scalici@inserm.fr.
authors.forename: Elodie
authors.initials: E
authors.lastname: Scalici
authors.affiliation: University of Burgundy, UFR Sciences de Santé de Dijon, Dijon, France.
authors.forename: Shaliha
authors.initials: S
authors.lastname: Bechoua
authors.affiliation: Department of Epidemiology, Bocage Hospital, CHU Dijon, Dijon, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Astruc
authors.affiliation: Biochemistry Department, CHU Dijon, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
authors.affiliation: INSERM UMR 866, lipids, Nutrition and Cancer, UFR of Medicine, Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.affiliation: ART Department, CHU de Dijon, Dijon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Drouineaud
authors.affiliation: Service de Biologie de la Reproduction-CECOS, CHU de Bordeaux, Centre Aliénor d'Aquitaine, Bordeaux, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Jimenez
authors.affiliation: ART-PGD Department, INSERM U1203, Arnaud de Villeneuve Hospital, CHU Montpellier, Montpellier, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Hamamah
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D015571:Follicular Fluid / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D054315:Oocyte Retrieval; D010062:Ovulation Induction; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D001055:Apolipoproteins B; D015415:Biomarkers; D006063:Chorionic Gonadotropin; D005640:Follicle Stimulating Hormone
keywords: Apolipoprotein B; Gonadotropins; Human follicular fluid; Human granulosa cells; IVF outcomes