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. 2015 Jul:54:26-36.
doi: 10.1016/j.reprotox.2014.12.002. Epub 2014 Dec 12.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Deirdre K Tucker  1 , Madisa B Macon  1 , Mark J Strynar  2 , Sonia Dagnino  3 , Erik Andersen  4 , Suzanne E Fenton  5
Affiliations

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Deirdre K Tucker et al. Reprod Toxicol. 2015 Jul.

Abstract

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain.

Keywords: C57Bl/6; CD-1; Estrous cycle; Mammary gland; Perfluorooctanoic acid; Puberty; Vaginal opening.

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Figures

Figure 1
Figure 1
Effects of PFOA treatment on serum hormone levels A) estradiol B) progesterone levels. All animals were sacrificed during estrus, with the exception of PND 21 when vaginal opening had not occurred. CD-1 litter/treatment group n=12-15 (PND 21), n=9-10 (PND 35) and n=8-10 (PND 56). C57Bl/6 litter n= 3-4 (PND 21) and n=3-9 (PND 61). Data presented as the mean ± SEM.
Figure 2
Figure 2
Mammary whole mount assessment of early and late pubertal glands in CD-1 offspring. Representative image of control A) PND 21, F) PND 35, and K) PND 56; 0.01 mg/kg B) PND 21, G) PND 35 and L) PND 56, 0.1 mg/kg C) PND 21, H)PND 35 and M)PND 56; 0.3 mg/kg D) PND 21, I) PND 35 and N) PND 56 and 1.0 mg/kg E) PND 21, J) PND 35 and O)PND 56. CD-1 n= 4-11 litters/treatment group. Significant inverse trends were noted between developmental scores and PFOA dose, indicating higher PFOA exposure was related to lower (more severe) developmental scores (p<0.05).
Figure 3
Figure 3
Mammary whole mount assessment of early and late pubertal glands in C57Bl/6 offspring. Representative image of control A) PND 21 and F) PND 61, 0.01 mg/kg B)PND 21 and G) PND 61, 0.1 mg/kg C) PND 21 and H)PND 61, 0.3 mg/kg D) PND 21 I) PND 61 and 1.0 mg/kg E) PND 21 and J) PND 61. C57Bl/6 n=2-10 litters/treatment group. Significant inverse trends were noted between developmental scores and PFOA dose, indicating higher PFOA exposure was related to lower (more severe) developmental scores (p<0.05).
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