Couples' urinary bisphenol A and phthalate metabolite concentrations and the secondary sex ratio

Bae, Jisuk; Kim, Sungduk; Louis, Germaine M. Buck

doi:10.1016/j.envres.2014.11.011

Cited by 16 publications

(12 citation statements)

References 77 publications

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“…Similar to other EDCs, phthalates display antiandrogenic properties (Chauvigne et al, 2009;Clewell et al, 2010Clewell et al, , 2013. In addition, both male and female preconception phthalate exposure has been associated with a range of adverse pregnancy and birth outcomes (Toft et al, 2012;Buck Louis et al, 2014;Bae et al, 2015;Smarr et al, 2015). The recent rise in the use of replacement phthalates and phthalate alternative compounds is a developing public health concern.…”

Section: Introductionmentioning

confidence: 99%

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment

Ashcraft

Whitcomb

et al. 2016

Hum. Reprod.

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STUDY QUESTION: Are preconception urinary concentrations of phthalates and phthalate alternatives associated with diminished early stage embryo quality in couples undergoing IVF?SUMMARY ANSWER: Male, but not female, urinary concentrations of select metabolites of phthalates and phthalate alternatives are associated with diminished blastocyst quality.WHAT IS KNOWN ALREADY: Although phthalates are endocrine disrupting compounds associated with adverse reproductive health, they are in widespread use across the world. Male and female preconception exposures to select phthalates have been previously associated with adverse reproductive outcomes in both the general population and in those undergoing IVF. STUDY DESIGN, SIZE, DURATION: This prospective cohort included 50 subfertile couples undergoing IVF in western Massachusetts. PARTICIPANTS/MATERIALS, SETTING, METHODS:This study includes the first 50 couples recruited from the Baystate Medical Center's Fertility Center in Springfield, MA, as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Relevant data from both partners, including embryo quality at the cleavage (Day 3) and blastocyst (Day 5) stages, were collected by clinic personnel during the normal course of an IVF cycle. A spot urine sample was collected from both male and female partners on the same day as semen sample procurement and oocyte retrieval. Concentrations of 17 urinary metabolite were quantified by liquid chromatography mass spectrometry and normalized via specific gravity. Generalized estimating equations were used to estimate odds ratios (OR) and 95% CI, with urinary phthalates and phthalate alternatives fitted as continuous variables and embryo quality as a binary variable. MAIN RESULTS AND THE ROLE OF CHANCE:The 50 couples contributed 761 oocytes, of which 423 progressed to the cleavage stage, 261 were high-quality cleavage stage embryos, 137 were transferrable quality blastocysts and 47 were high-quality blastocysts. At the cleavage stage, male urinary monoethyl phthalate concentrations were positively associated with high-quality cleavage stage embryos (OR = 1.20, 95% CI 1.01-1.43, P = 0.04); no other significant associations were observed at this stage. At the blastocyst stage, male urinary concentrations of monobenzyl phthalate (OR = 0.55, 95% CI 0.36-0.84, P = 0.01), mono-3-hydroxybutyl phthalate (OR = 0.37, 95% CI 0.18-0.76, P = 0.01), mono-n-butyl phthalate (OR = 0.55, 95% CI 0.42-0.73, P < 0.01) and monomethyl phthalate (OR = 0.39, 95% CI 0.26-0.60, P < 0.01) were inversely associated with high-quality blastocysts. A borderline statistically significant relationship was observed for male concentrations of mono (2-ethylhexyl) phthalate (OR = 0.52, 95% CI 0.27-1.00, P = 0.05) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (OR = 0.21, 95% CI 0.04-1.03, P = 0.05) at the blastocyst stage. Similar inverse associations were observed between male urinary phthalate metabolite concentrations and likelihood of transferrable quality blastocysts. For femal...

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Section: Introductionmentioning

confidence: 99%

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment

Ashcraft

Whitcomb

et al. 2016

Hum. Reprod.

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“…A total of five studies (Buck Louis et al, 2014 [RefID 4599]; Bae et al, 2015 [RefID 347]; Dodge et al, 2015 [RefID 1648]; Goldstone et al, 2015 [RefID 2304]; Buck Louis et al, 2018 [RefID 12602]) in three different cohorts examined the relationship between urinary concentrations of BPA and fertility in males and females.…”

Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Lambré¹,

Baviera²,

Bolognesi³

et al. 2023

EFS2

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In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

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“…Similar to the findings among the fertility clinic patients, Buck-Louis et al did not find association between paternal urinary BPA concentrations and time to pregnancy (fecundity odds ratio (FOR) was 1.04; 95% CI, 0.91, 1.18) (43). However, in an analysis focused on secondary sex ratio (ratio of male to female births) among couples in the LIFE Study who had a singleton live birth, higher paternal urinary BPA concentrations were significantly associated with fewer male births (RR= 0.77 per 1 SD increase in urinary BPA; 95% CI, 0.62–0.95) (44). In both the EARTH and LIFE Studies, the men had, on average, low urinary BPA concentrations [unadjusted GM (IQR) was 1.6 ng/mL (0.8, 2.8 ng/mL), and (5 th , 95 th percentiles) was 0.5 ng/mL (0.4, 0.6 ng/mL), respectively].…”

Section: Bpa and Couple Reproductive Outcomesmentioning

confidence: 99%

Effects of bisphenol A on male and couple reproductive health: a review

Mínguez-Alarcón

Hauser

Gaskins

2016

Fertility and Sterility

115

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Bisphenol A (BPA) is a ubiquitous environmental toxicant with endocrine-disrupting properties and suspected to affect human reproduction. Yet in humans, the studies exploring the effect of this BPA on male reproductive health including semen quality, reproductive hormones, and couple fecundity and fertility, have produced inconsistent results. The objective of this manuscript was to summarize the effects of male exposure to BPA on markers of testicular function and couple reproductive outcomes. Of the five studies on male BPA exposure and reproductive hormones, all found significant associations with at least one reproductive hormone; however no consistent relations were observed across studies. Similarly, five studies evaluated the relation between BPA and semen quality and while the majority reported negative associations with various parameters, there were few consistent trends across studies. Finally, the three studies which have examined male urinary BPA levels and couple reproductive outcomes did not find associations, with the exception being a link with lower secondary sex ratio (or greater female excess). Overall, while the literature on this topic is growing, the evidence supporting a link between male BPA exposure and male reproductive health remains limited and inconclusive. Reasons for the discrepancies in results could include, but are not limited to, differences in: study populations (e.g. fertile vs. subfertile men), BPA exposure levels (occupationally exposed vs. non-occupationally exposed), study procedures used to collect and measure urinary BPA (e.g. using one urine sample to characterize exposure vs. multiple samples), sample sizes, and study design (e.g. cross-sectional vs. prospective). Based on the available evidence, there is insufficient evidence to conclude that exposure to BPA, at low to moderate levels, has a negative effect on reproductive outcomes in men. Clearly, further studies are needed to further clarify the role of this ubiquitous endocrine disrupting chemical on male reproductive health.

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Couples' urinary bisphenol A and phthalate metabolite concentrations and the secondary sex ratio

Cited by 16 publications

References 77 publications

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Effects of bisphenol A on male and couple reproductive health: a review

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