N Gatimel1, M Z Lacroix2, S Chanthavisouk1, N Picard-Hagen2, V Gayrard2, J Parinaud1, R D Léandri3. 1. Médecine de la Reproduction, Centre Hospitalier Universitaire de Toulouse, F-31059 Toulouse, France Université de Toulouse; UPS; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), F-31059 Toulouse, France. 2. Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d'Ingénieurs de Purpan, Université Paul Sabatier, F-31076 Toulouse, France. 3. Médecine de la Reproduction, Centre Hospitalier Universitaire de Toulouse, F-31059 Toulouse, France Université de Toulouse; UPS; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), F-31059 Toulouse, France leandri.r@chu-toulouse.fr.
Abstract
STUDY QUESTION: Do the embryo culture media and plastic materials used during assisted reproductive technology (ART) laboratory procedures expose embryos to bisphenol A (BPA)? SUMMARY ANSWER: BPA was not detected in embryo culture media or protein supplements at concentrations above those encountered in normal patient serum and follicular fluids. WHAT IS KNOWN ALREADY: BPA is strongly suspected of altering the epigenome during mammalian development. Medical devices have been shown to be a source of BPA exposure in adult and neonatal intensive care units. STUDY DESIGN, SIZE, DURATION: An analytical study of ART culture media and plastic labware products was performed under conditions close to routine practice and if BPA was detected, tests were carried out under more stringent conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two single-step embryo culture media, two sequential media and three different protein supplements [a purified human serum albumin (HSA), a synthetic serum substitute, and a recombinant HSA] were tested for BPA. Thirty-three different plastic consumables, used from oocyte collection through to embryo transfer, were tested for their ability to leach BPA into their surrounding environment.BPA concentrations were measured according to a previously described liquid chromatography/mass spectrometry method. This method is linear over the calibration range from 0.5 to 100 ng/ml using a linear model weighted by 1/X² and validated in terms of selectivity, linearity, repeatability, reproducibility and limit of quantification (0.5 ng/ml). MAIN RESULTS AND THE ROLE OF CHANCE: Neither the culture media nor the protein supplements were shown to contain detectable levels of BPA. None of the plastic materials leached BPA into the surrounding medium at levels higher than the upper limit detected previously in serum and follicular fluids in women (about 2 ng/ml). However, the plastic of the three tested strippers used for oocyte denudation/embryo handling did contain BPA. Two of these strippers are made with polycarbonate, a plastic whose synthesis is known to require BPA. LIMITATIONS, REASONS FOR CAUTION: This study is limited to the ART media and materials tested here and using a BPA assay with a limit of quantification at 0.5 ng/ml. A minimum volume was required for testing, and one type of plastic labware could not be tested in conditions identical to those in routine use. WIDER IMPLICATIONS OF THE FINDINGS: Although we demonstrated that some plastic materials used in ART contain BPA, under routine conditions none appear capable of leaching BPA at levels higher than those from maternal internal exposure. However, BPA is strongly suspected of altering the epigenome. Since important epigenetic modifications occur in the early embryonic stage, it is questionable whether plastics that contain BPA, polycarbonate in particular, should be used in the manufacture of plastic consumables for ART procedures. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the Agence de Biomédecine (AOR 2012) and by a grant from the French Ministry of Health (Clinical Research Hospital Program 2012; no.12-018-0560). The authors declared no competing interest.
STUDY QUESTION: Do the embryo culture media and plastic materials used during assisted reproductive technology (ART) laboratory procedures expose embryos to bisphenol A (BPA)? SUMMARY ANSWER: BPA was not detected in embryo culture media or protein supplements at concentrations above those encountered in normal patient serum and follicular fluids. WHAT IS KNOWN ALREADY: BPA is strongly suspected of altering the epigenome during mammalian development. Medical devices have been shown to be a source of BPA exposure in adult and neonatal intensive care units. STUDY DESIGN, SIZE, DURATION: An analytical study of ART culture media and plastic labware products was performed under conditions close to routine practice and if BPA was detected, tests were carried out under more stringent conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two single-step embryo culture media, two sequential media and three different protein supplements [a purified human serum albumin (HSA), a synthetic serum substitute, and a recombinant HSA] were tested for BPA. Thirty-three different plastic consumables, used from oocyte collection through to embryo transfer, were tested for their ability to leach BPA into their surrounding environment.BPA concentrations were measured according to a previously described liquid chromatography/mass spectrometry method. This method is linear over the calibration range from 0.5 to 100 ng/ml using a linear model weighted by 1/X² and validated in terms of selectivity, linearity, repeatability, reproducibility and limit of quantification (0.5 ng/ml). MAIN RESULTS AND THE ROLE OF CHANCE: Neither the culture media nor the protein supplements were shown to contain detectable levels of BPA. None of the plastic materials leached BPA into the surrounding medium at levels higher than the upper limit detected previously in serum and follicular fluids in women (about 2 ng/ml). However, the plastic of the three tested strippers used for oocyte denudation/embryo handling did contain BPA. Two of these strippers are made with polycarbonate, a plastic whose synthesis is known to require BPA. LIMITATIONS, REASONS FOR CAUTION: This study is limited to the ART media and materials tested here and using a BPA assay with a limit of quantification at 0.5 ng/ml. A minimum volume was required for testing, and one type of plastic labware could not be tested in conditions identical to those in routine use. WIDER IMPLICATIONS OF THE FINDINGS: Although we demonstrated that some plastic materials used in ART contain BPA, under routine conditions none appear capable of leaching BPA at levels higher than those from maternal internal exposure. However, BPA is strongly suspected of altering the epigenome. Since important epigenetic modifications occur in the early embryonic stage, it is questionable whether plastics that contain BPA, polycarbonate in particular, should be used in the manufacture of plastic consumables for ART procedures. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the Agence de Biomédecine (AOR 2012) and by a grant from the French Ministry of Health (Clinical Research Hospital Program 2012; no.12-018-0560). The authors declared no competing interest.
Authors: Kelly A Campen; Katherine M Kucharczyk; Benjamin Bogin; Julie M Ehrlich; Catherine M H Combelles Journal: Hum Reprod Date: 2018-05-01 Impact factor: 6.918
Authors: A Togola; A Desmarchais; O Téteau; C Vignault; V Maillard; C Buron; S Bristeau; F Guérif; A Binet; S Elis Journal: Hum Reprod Date: 2021-03-18 Impact factor: 6.918
Authors: Isabel J Ricke; Ashley Oglesby; Grace R Lyden; Emily S Barrett; Stacey Moe; Ruby H N Nguyen Journal: Int J Environ Res Public Health Date: 2022-03-04 Impact factor: 3.390