Abstract

BackgroundRadiation exposure is known to cause accelerated aging and damage to the ovary, but the contribution of indirect versus direct effects is not well understood. We used the Small Animal Radiation Research Platform (SARRP) (Xstrahl) to deliver radiation to precise fields equivalent to clinical practice, allowing us to investigate systemic versus targeted damage in a structure as small as the mouse ovary. The X-ray dose was kept constant at 1 Gy, but the field varied. Mice either received total body irradiation (TBI), radiation targeted to both ovaries (T2), or radiation targeted to one ovary (left) while the contralateral ovary (right) was spared (T1). Sham mice, handled similarly to the other cohorts but not exposed to radiation, served as controls. Two weeks post-exposure, ovaries were harvested and analyzed histologically to identify and count follicles within each ovary.ResultsRadiation significantly reduced primordial follicles in the TBI and T2 cohorts compared to the Sham cohort. There were no significant differences between these two irradiated groups. These findings suggest that at 1 Gy, the extent of damage to the ovary caused by radiation is similar despite the different delivery methods. When investigating the T1 cohort, targeted ovaries showed a significant decrease in primordial and growing follicles compared to non-targeted contralateral ovaries.ConclusionsThese findings demonstrate that the SARRP is an effective strategy for delivering precise ionizing radiation to small organs such as mouse ovaries. Such tools will facilitate identifying the relative risks to ovarian function associated with different radiation fields as well as screening the efficacy of emerging fertoprotective agents.

Highlights

  • Radiation exposure is known to cause accelerated aging and damage to the ovary, but the contribution of indirect versus direct effects is not well understood

  • We did not observe any difference in the total number of serial sections obtained per ovary, suggesting that radiation exposure did not cause dramatic changes in ovarian size (Fig. 1e)

  • These results demonstrate that the Small Animal Radiation Research Platform (SARRP) is able to deliver precise radiation to a field as small as a single ovary, we wanted to assess whether there was any off-target damage to the non-targeted contralateral ovary

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Summary

Results

Use of the SAARP to examine systemic versus targeted effects of ionizing radiation on ovarian tissue We have previously demonstrated that a single dose of 1 Gy TBI is sufficient to cause a significant reduction in ovarian follicles 2 weeks post-exposure in adult female CD1 mice, whereas a lower dose of 0.1 Gy is not [37]. Comparison of ovarian damage following targeted radiation to a single ovary relative to the non-targeted contralateral ovary To examine potential off-target effects of radiation damage to the ovary, we used the SAARP to deliver precise radiation to one ovary while sparing the contralateral ovary for each mouse (Fig. 1a; T1 cohort) In this case, the non-targted ovary served as an internal control or a within-animal comparison, which is typically not possible, i.e., when only TBI is used. Based on gross assessment of ovarian histological sections, both non-targeted and targeted ovaries still had antral follicles and corpora lutea present in the tissue similar to what we observed in the TBI and T2 cohorts; providing evidence of follicle growth and estrous cyclicity (Fig. 5a and b). When examining the growing follicles according to class, there did appear to be a decrease in primary follicles between the Sham and non-targeted cohorts, suggesting that primary follicles may be sensitive to off-target radiation effects (Additional file 4)

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