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Dermal exposure to the UV filter benzophenone-3 during early pregnancy affects fetal growth and sex ratio of the progeny in mice

Abstract

The aim of this study was to analyze whether dermal exposure to benzophenone 3 (BP-3) during pregnancy affects critical parameters of pregnancy, and whether this exposure may affect the outcome of a second pregnancy in mice. Pregnant mice were exposed to 50-mg BP-3/kg body weight/day or olive oil (vehicle) from gestation day (gd) 0 to gd6 by dermal exposure. High-frequency ultrasound imaging was used to follow up fetal and placental growth in vivo. Blood flow parameters in uterine and umbilical arteries were analyzed by Doppler measurements. Mice were killed at gd5, gd10, and gd14 on the first pregnancy, and at gd10 and 14 on the second pregnancy. The weight of the first and second progenies was recorded, and sex ratio was analyzed. BP-3 levels were analyzed in serum and amniotic fluid. BP-3 reduced the fetal weight at gd14 and feto-placenta index of first pregnancy, with 16.13% of fetuses under the 5th percentile; arteria uterina parameters showed altered pattern at gd10. BP-3 was detected in serum 4 h after the exposure at gd6, and in amniotic fluid at gd14. Offspring weight of first progeny was lower in BP-3 group. Placenta weights of BP-3 group were decreased in second pregnancy. First and second progenies of mothers exposed to BP-3 showed a higher percentage of females (female sex ratio). Dermal exposure to low dose of BP-3 during early pregnancy resulted in an intrauterine growth restriction (IUGR) phenotype, disturbed sex ratio and alterations in the growth curve of the offspring in mouse model.

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Acknowledgements

We are very thankful to Stefanie Langwisch, who was in charge of the mouse colonies and to Markus Scharm, Walter Nykolajczuk and Laura Bergero for his technical support and Abud Julián. This work was funded by grants from ANPCyT (Agencia Nacional de Promoción Científica y Tecnológica) Projects PICT 2017-0340 and PICT 2017-1532; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas, Project PIP-2015 Nº 0111) and Universidad Nacional del Litoral (Project CAI + D 2016-50120150100110LI) and grants 01DN16021 from DLR/BMBF and from the German Research Foundation (DFG, ZE 526/12-1) to ACZ. Mobility grants from MinCyT (Ministerio de Ciencia y Tecnología, Argentina AL//15/06) and BMBF (Germany) to HAR and ACZ enabled the interchange of scientists between Argentina and Germany. CGS and CMT are postdoctoral fellows from CONICET. MLZ, MJC and HAR are career Investigators of CONICET.

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Contributions

Conceptualization: ACZ and HAR; Methodology: CGS, NM, AS, CMT, MJC. Full analysis and investigation: CGS, NM, AS; MLZ. Writing–original draft preparation: CGS, HAR, MLZ; NM. Writing–review and editing: ACZ, HAR. Funding acquisition: ACZ, HAR, MJC; CMT. Resources: ACZ, HAR. Supervision: ACZ, HAR.

Corresponding author

Correspondence to Horacio Adolfo Rodriguez.

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The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted: Landesverwaltungsamt Sachsen Anhalt: 42502-21296UniMD, Magdeburg, Germany; Ethical committee of the Facultad de Bioquímica y Ciencias Biológicas, UNL, Santa Fe, Argentina, CE2018-62. The experiments were conducted by authorized persons according to the Guide for Care and Use of Animals in Agriculture Research and Teaching. This article does not contain any studies with human participants performed by any of the authors.

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Santamaria, C.G., Meyer, N., Schumacher, A. et al. Dermal exposure to the UV filter benzophenone-3 during early pregnancy affects fetal growth and sex ratio of the progeny in mice. Arch Toxicol 94, 2847–2859 (2020). https://doi.org/10.1007/s00204-020-02776-5

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  • DOI: https://doi.org/10.1007/s00204-020-02776-5

Keywords

  • Benzophenone-3
  • Pregnancy
  • Placenta
  • Development
  • Sex ratio