NanoTIO2 (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice

Anne Mette Zenner Boisen,Håkan Wallin,Carole L Yauk,Thomas Shipley,Karin Sørig Hougaard,Petra Jackson,Ulla Vogel

doi:10.1186/1743-8977-9-19

Abstract

BackgroundParticulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR) loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development). Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO2) produces a long-lasting inflammatory response in mice, it was chosen for the present study.FindingsPregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO2 UV-Titan L181 (~42.4 mg UV-Titan/m3) or filtered clean air on gestation days (GD) 8–18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring) of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls). ESTR mutation rates of 0.029 (maternal allele) and 0.047 (paternal allele) in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele) and 0.061 (paternal allele).ConclusionsWe found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.

Highlights

Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer
We found no evidence for increased Expanded simple tandem repeat (ESTR) mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females
Pulmonary exposure to nanoTiO2 causes inflammation in rodents [9,16] and we recently found that a single UV-Titan instillation induced an inflammatory response in mice after 1 day [12,17]

Summary

Background

Mutations in male and female gametes may lead to detrimental inherited effects in subsequent generations. Human exposure to particulate air pollution (PAP) has been shown to adversely affect germ cells in males [1]. A recent study showed that prenatal exposure to 1 Gy of acute irradiation on GD12 resulted in a 1.94-fold increase in ESTR mutations in the offspring of irradiated female mice [22,23]. We hypothesized that prenatal exposure to NPs will affect female germline ESTR mutation frequency during stages of active cell division, similar to what has been found for male germline cells [1]. The present study investigates TiO2 nanoparticle-induced effects on female germline DNA by exposing pregnant female mice (P) to nanoTiO2 or clean filtered air via inhalation and subsequently mating their offspring (F1) with unexposed males. The observed F1 female germline ESTR mutation frequency was calculated by comparing allele size in the F2 offspring to their mother’s allele size to quantify repeat gains and losses

Methods

Results and discussion

13 TiO2 and 12 Controls

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