Differential sensitivity of inbred mouse strains to ovarian damage in response to low-dose total body irradiation†.

Natalie Quan, Lacey R Harris, Ritika Halder, Camille V Trinidad, Brian W Johnson, Shulamit Horton, Bruce F Kimler, Michele T Pritchard, Francesca E Duncan

Biology of reproduction 2020 Feb 12

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Radiation induces ovarian damage and accelerates reproductive aging. Inbred mouse strains exhibit differential sensitivity to lethality induced by total body irradiation (TBI), with the BALB/cAnNCrl (BALB/c) strain being more sensitive than the 129S2/SvPasCrl (129) strain. However, whether TBI-induced ovarian damage follows a similar pattern of strain sensitivity is unknown. To examine this possibility, female BALB/c and 129 mice were exposed to a single dose of 1 Gy (cesium-137 γ) TBI at 5 weeks of age, and ovarian tissue was harvested for histological and gene expression analyses 2 weeks post exposure. Sham-treated mice served as controls. 1 Gy radiation nearly eradicated the primordial follicles and dramatically decreased the primary follicles in both strains. In contrast, larger growing follicles were less affected in the 129 relative to BALB/c strain. Although this TBI paradigm did not induce detectable ovarian fibrosis in either of the strains, we did observe strain-dependent changes in osteopontin (Spp1) expression, a gene involved in wound healing, inflammation, and fibrosis. Ovaries from BALB/c mice exhibited higher baseline Spp1 expression that underwent a significant decrease in response to radiation relative to ovaries from the 129 strain. A correspondingly greater change in the ovarian matrix, as evidenced by reduced ovarian hyaluronan content, was also observed following TBI in BALB/c mice relative to 129 mice. These early changes in the ovary may predispose BALB/c mice to more pronounced late effects of TBI. Taken together, our results demonstrate that aspects of ovarian damage mirror other organ systems with respect to overall strain-dependent radiation sensitivity. © The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Natalie Quan, Lacey R Harris, Ritika Halder, Camille V Trinidad, Brian W Johnson, Shulamit Horton, Bruce F Kimler, Michele T Pritchard, Francesca E Duncan. Differential sensitivity of inbred mouse strains to ovarian damage in response to low-dose total body irradiation†. Biology of reproduction. 2020 Feb 12;102(1):133-144