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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)133-144
Number of pages12
JournalBiology of reproduction
Volume102
Issue number1
DOIs
StatePublished - Feb 12 2020

Keywords

  • fertility preservation
  • follicle
  • ovarian reserve
  • ovary
  • radiation

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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