Thyroid hormone triiodothyronine does not protect ovarian reserve from DNA damage induced by X-ray and cisplatin

Cancer therapy can induce premature ovarian insufficiency, necessitating methods for preserving fertility in female cancer patients. However, the only accepted clinical practice for doing so is cryopreservation of embryos, unfertilized ova, and ovarian tissue, despite potential options such as in vitro maturation of follicles. Therefore, considerable interest has arisen in fertoprotective agents, with research on rat ovarian granulosa cells suggesting that triiodothyronine (T3) regulates an anti-apoptosis mechanism that protects the ovarian reserve from paclitaxel-induced DNA damage. In this study, we used postnatal day 5 mouse ovary to confirm the existence of T3 thyroid hormone receptor (THR), as well as to investigate the potential protective effects of T3 against cisplatin- and X-ray-induced apoptosis. We also tested the potential anti-apoptotic effect of T3 in the breast cancer cell line MDA-MB-231.

We treated cultured mouse ovaries with varying concentration of T3 and 4 μM cisplatin and 0.2 Gy X-ray. Real-time PCR, histological analysis, immunoblot analysis, and immunofluorescence were performed to assess the potential anti-apoptotic effects of T3.

We confirmed that THR alpha and beta are expressed in the mouse ovary. T3 (0.1, 1, 10, 100 nM, and 1 µM) does not protect ovarian reserve from cisplatin- or X-ray-induced apoptosis or DNA damage. Similarly, it does not protect mouse granulosa cells and MDA-MB-231 cells from cisplatin- or X-ray-induced apoptosis.

Our findings suggest that T3 is ineffective as a fertoprotective agent, and its candidacy as a potential agent to preserve fertility should be reconsidered.