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

Arch Toxicol. 2020 Aug;94(8):2847-2859. doi: 10.1007/s00204-020-02776-5. Epub 2020 May 19.

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.

Keywords: Benzophenone-3; Development; Placenta; Pregnancy; Sex ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Amniotic Fluid / metabolism
  • Animals
  • Benzophenones / administration & dosage
  • Benzophenones / blood
  • Benzophenones / toxicity*
  • Female
  • Fetal Development / drug effects*
  • Fetal Growth Retardation / blood
  • Fetal Growth Retardation / chemically induced*
  • Fetal Growth Retardation / physiopathology
  • Gestational Age
  • Male
  • Maternal Exposure
  • Maternal-Fetal Exchange
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Placentation / drug effects
  • Pregnancy
  • Risk Assessment
  • Sex Ratio*
  • Sunscreening Agents / administration & dosage
  • Sunscreening Agents / metabolism
  • Sunscreening Agents / toxicity*

Substances

  • Benzophenones
  • Sunscreening Agents
  • oxybenzone