title: Endocrine-disrupting chemicals in human follicular fluid impair in vitro oocyte developmental competence.
abstract: BACKGROUND
  Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called 'endocrine-disrupting chemicals' (EDCs) or 'endocrine disruptors', can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum.
  
  
  METHODS
  Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination.
  
  
  RESULTS
  Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even when the analysis is adjusted for age, estradiol concentration, BMI, fertilization procedure and male subfertility as explanatory variables. The strong correlations between the EDC concentrations in serum and follicular fluid (r ≥ 0.93) allowed us to build regression models, which accurately predict EDC concentrations in the follicular fluid based on serum samples.
  
  
  CONCLUSIONS
  An overall higher EDC contamination in the follicular micro-environment was associated with a decreased fertilization rate and consequently with a lower chance of an oocyte to develop into a high-quality embryo. In addition, EDC concentrations in serum were reliable predictors of the contamination status of the follicular micro-environment.
authors.affiliation: Gamete Research Center, Laboratory for Veterinary Physiology and Biochemistry, Department of Veterinary Sciences,  University of Antwerp, Universiteitsplein 1, 2610 Wilrijk,  Belgium.
authors.forename: Evi M L
authors.initials: EM
authors.lastname: Petro
authors.forename: Jo L M R
authors.initials: JL
authors.lastname: Leroy
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Diane
authors.initials: D
authors.lastname: De Neubourg
authors.forename: Alin C
authors.initials: AC
authors.lastname: Dirtu
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Pauw
authors.forename: Peter E J
authors.initials: PE
authors.lastname: Bols
mesh_terms: D000328:Adult; D002849:Chromatography, Gas; D052244:Endocrine Disruptors / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000737:chemistry*; D055768:Halogenated Diphenyl Ethers / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D007247:Infertility, Female / Q000628:therapy; D013058:Mass Spectrometry; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D052244:Endocrine Disruptors; D055768:Halogenated Diphenyl Ethers; D006843:Hydrocarbons, Chlorinated; D011078:Polychlorinated Biphenyls