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Serum unconjugated bisphenol A concentrations in men may influence embryo quality indicators during in vitro fertilization

https://doi.org/10.1016/j.etap.2011.06.003Get rights and content

Abstract

Here we assess bisphenol A (BPA) in couples undergoing in vitro fertilization (IVF) and indicators of embryo quality; embryo cell number (ECN) and embryo fragmentation score (EFS). Twenty-seven couples provided serum on the day of oocyte retrieval. Unconjugated BPA was measured by HPLC with Coularray detection. Odds ratios (OR) were generated using ordinal logistic regression including female and male BPA concentrations, age and race, and day of embryo transfer for ECN. Inverse associations are suggested for male BPA with ECN (OR = 0.70, P = 0.069), and EFS (OR = 0.54, P = 0.009), but not for women. Male BPA exposure may affect embryo quality during IVF.

Highlights

Bisphenol A (BPA) is a plastic monomer with estrogenic and aneugenic properties. ► We measured serum unconjugated BPA in couples receiving in vitro fertilization (IVF). ► Male, but not female BPA concentration was associated with embryo quality indicators. ► BPA exposure in the male partner of couples undergoing IVF may affect embryo quality.

Introduction

Growing evidence indicates that bisphenol A (BPA), a widely used plastic monomer, is a reproductive toxicant of public health importance (NTP, 2008). However, this issue remains controversial (Goodman et al., 2009, Vandenberg et al., 2009). BPA has been shown to disrupt oocyte nuclear competence during murine folliculogenesis (Hunt et al., 2003), with deleterious effects on nuclear maturation including increased mitotic spindle defects and meiotic arrest. BPA also binds to ‘classical’ nuclear estrogen receptors (Richter et al., 2007, Wetherill et al., 2007), and to ‘non-classical’ membrane-associated estrogen receptors (Luconi et al., 1999, Wozniak et al., 2005). However, the clinical implications of BPA estrogen receptor binding remain unclear (Luconi et al., 2001).

The potential public health significance of BPA-associated reproductive toxicity is underscored by its detection in 93% of the U.S. population (Calafat et al., 2008), as well as in human reproductive fluids (Inoue et al., 2002, Kaddar et al., 2009). In this preliminary study, we augment our prior work (Fujimoto et al., 2011b) describing an inverse association between female BPA concentrations and oocyte fertilization rates during in vitro fertilization (IVF). The current study describes associations between BPA concentrations and embryo quality indicators among a subset of couples for whom embryos were generated during IVF.

Section snippets

Materials and methods

The current analysis comprises a subsample of 27 couples participating in the previously described prospective cohort Study of Metals and Assisted Reproductive Technologies (SMART) (Bloom et al., 2011). This dataset includes only those members of the SMART cohort for whom embryos were generated during IVF, and for whom a sufficient volume of serum was available to complete BPA analysis in both the female patient and her male partner. Informed consent was obtained from all participants, and the

Results

Demographics for the SMART cohort have been previously described (Bloom et al., 2011). Among female and male SMART participants producing embryos, there are no meaningful differences in serum BPA concentration, age, or race (P  0.15 by Mann–Whitney U-test or Fisher's Exact test as appropriate) between subjects included in this analysis and those excluded (data not shown). The current subsample produced a median of 6.0 embryos (range 1.0–14.0) per couple, with median ECN equal to 6.4 (range

Discussion

The effects on embryo quality indicated by this study for only paternal serum BPA concentrations were unanticipated a priori. It is tempting to contemplate that the inverse association suggested for early embryo cleavage rate, may result from sperm integrity disruption. Whereas the nucleic acid sequence of sperm DNA does not appear to be directly altered by BPA (Bennetts et al., 2008), other structural changes have been reported in BPA-exposed sperm (Toyama et al., 2004), and structural changes

Conclusions

In summary, we describe inverse associations between serum unconjugated BPA concentrations measured in the male partners of women undergoing IVF, and embryo quality indicators. To our knowledge, these data represent the first evidence of male BPA exposure effects on human embryo quality and suggest a role for sperm quality on early embryo development. The limited sample size and scope of this study make these results preliminary; however, the provocative nature of these results warrants

Conflict of interest

Nothing declared.

Acknowledgements

We would like to thank Julia Sandler, Giulia Conti, and Natasha Narayan for their expert assistance with clinical recruitment and specimen processing.

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      Citation Excerpt :

      No age-specific differences in the concentrations of BPA and its metabolites were observed. Concentrations of BPA in serum and those reported in human blood matrixes from around the world are generally on the same order of magnitude [(He et al., 2009; Sajiki et al., 1999; Yoshimura et al., 2002; Liu et al., 2006; Bloom et al., 2011; Wan et al., 2013; Zhou et al., 2013)]. For example, the mean serum level of BPA (0.53 ng/mL) is similar to that in pooled Japanese serum (n = 20, mean 0.33−0.59 ng/mL) (Yoshimura et al., 2002), but lower than that in plasma from Hong Kong adults (n = 153, 0.95 ng/mL) (Wan et al., 2013).

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    Funding sources: Institutional discretionary research funds available to Drs. Bloom and Fujimoto were used to support this work. This research was also supported in part by an NIEHS grant ES018764 provided to Dr. vom Saal.

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