title: Bisphenol-A and human oocyte maturation in vitro.
abstract: OBJECTIVE
  Does exposure to bisphenol-A (BPA) affect the maturation of human oocytes in vitro?
  
  
  CONCLUSIONS
  There was a dose-response association of BPA exposure with altered human oocyte maturation in vitro.
  
  
  BACKGROUND
  There is widespread exposure of the general population to BPA. BPA has been detected in the human follicular fluid. Animal studies have shown that BPA exposure is associated with maturation arrest and spindle abnormalities in maturing oocytes.
  
  
  METHODS
  A randomized trial, using 352 clinically discarded oocytes from 121 patients.
  
  
  METHODS
  The study population was drawn from patients undergoing IVF/ICSI cycles in our program at Brigham and Women's Hospital from March 2011 to April 2012. Oocytes from only one cycle for each patient were included in the study. Cycles with at least two germinal vesicle stage oocytes were included with random allocation of one oocyte to culture for 30 h without BPA and remaining sibling oocytes to medium-containing BPA (20, 200 ng/ml or 20 µg/ml). Oocytes were fixed and labeled for tubulin, actin and chromatin and examined with immunofluorescence and confocal microscopy. Oocytes were assessed for meiotic stage (n = 292), and those at metaphase II (MII, n = 175) were further classified according to their spindle configurations and patterns of chromosome alignment. McNemar's test was used to compare dichotomized maturation status. Generalized estimating equations were used to account for the correlation between oocytes from the same woman and for the spindle analysis.
  
  
  RESULTS
  As the BPA dose increased, there was a decrease in the percentage of oocytes that progressed to MII (P = 0.002) and increases in the percentage of oocytes that were degenerated (P = 0.01) or that had undergone spontaneous activation (P = 0.007). Among MII oocytes, as the BPA dose increased, there was a significant trend (by test for trend) for a decreased incidence of bipolar spindles (P < 0.0001) and aligned chromosomes (P = 0.02).
  
  
  CONCLUSIONS
  Although we used sibling oocytes to overcome potential confounders, such as infertility diagnosis and maternal age, additional studies with a larger number of oocytes are required to confirm the present results. Having access only to clinically discarded oocytes, we were limited to evaluating only those oocytes that failed to mature in vivo despite having been exposed to gonadotrophin stimulation and the ovulatory trigger of HCG.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study investigating the effect of BPA on oocyte meiotic maturation, spindle morphology and chromosome alignment in human oocytes. Together with prior animal studies, the data support the negative influences of BPA on cell cycle progression, spindle architecture and chromosome organization during oocyte maturation. Furthermore, the increased rates of abnormal maturation in oocytes exposed to BPA may be relevant to our understanding of the decrease in fertility reported in the last decades.
  
  
  BACKGROUND
  This study was funded by the NIEHS Center Grant Pilot Project (P30-ES000002). R.M. was sponsored by a fellowship from the Environmental Health Fund, Israel and by the Frederick L. Hisaw Endowment, Harvard School of Public Health. There are no conflicts of interest.
  
  
  BACKGROUND
  n/a.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Machtinger
authors.forename: Catherine M H
authors.initials: CM
authors.lastname: Combelles
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
authors.forename: Katharine F
authors.initials: KF
authors.lastname: Correia
authors.forename: Paige
authors.initials: P
authors.lastname: Williams
authors.forename: Russ
authors.initials: R
authors.lastname: Hauser
authors.forename: Catherine
authors.initials: C
authors.lastname: Racowsky
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000633:toxicity*; D018929:Cell Culture Techniques; D002875:Chromosomes / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D008540:Meiosis / Q000187:drug effects; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D010636:Phenols / Q000633:toxicity*; D008941:Spindle Apparatus / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: bisphenol-A; human oocyte; in vitro; meiosis; meiotic maturation
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