mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy
Abstract
A major unresolved issue for premenopausal women undergoing chemotherapy is infertility due to the loss of nonrenewable ovarian primordial follicles. We show that pharmacologic down-regulation of the mammalian/mechanistic target of rapamycin (mTOR) pathway during chemotherapy in a mouse model prevents activation of primordial follicles, preserves ovarian function, and maintains normal fertility using clinically available inhibitors of mTOR complex (C)1 and mTORC1/2. These findings represent a feasible pharmacologic approach for preservation of ovarian function and fertility during treatment with conventional chemotherapy.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2017
- DOI:
- 10.1073/pnas.1617233114
- Bibcode:
- 2017PNAS..114.3186G