Ovarian scaffolds promoted mouse ovary recovery from cyclophosphamide damage

Abstract

There is growing evidence to suggest that scaffold of tissue can promote the tissue reparation. In this study, we investigate the effects of ovarian scaffolds on the reparation of cyclophosphamide (CPA) damaged mice ovaries. The mice were first administered with CPA, was then either transplanted an ovarian scaffold into each ovarian bursa for the experimental group (EG) or underwent sham surgery as the control (CG). To evaluate the extent of ovarian damage caused by CPA, a third group which did not undergo any treatment was included for the normal control (NG). Their ovaries were harvested for examination at day 30, 60, and 90 post CPA injection. We found that in EG, the number of all types of follicles in the ovaries remained almost the same throughout. The numbers of follicles were not significantly different from CG, except at day 60, where in CG the numbers of each type of follicle decreased to basal levels. The decrease in the number of ovarian follicles at day 60 in CG was mirrored by the significant increase in the number of apoptotic granulosa cells in the follicles, and was corroborated further by the basal levels of serum estradiol. Furthermore, we observed a significant decrease in collagen composition preceded by macrophage polarization, and elevation of inflammatory cytokine expression in the ovaries of the EG compared to the CG at day 60. We concluded that ovarian scaffolds can effectively protect primordial follicles from CPA-damage and promote the reparation of CPA-damaged ovaries. This research establishes a proof of concept for the future treatment of chemo-damaged ovaries.