Graft-versus-host disease targets ovary and causes female infertility in mice
Female survivors of allogeneic HSCT have a high incidence of ovarian dysfunction. While this has been assumed to be an effect of conditioning, the role of GVHD on ovarian function has not been explored.
Mouse models of GVHD were established with three different conditioning regimens - BuCy myeloablative, BuCy RIC, and TBI followed by splenocyte transplant. One cohort received prophylaxis with prednisolone, cyclosporine, or tacrolimus while a control cohort had no prophylaxis. Fertility and ovarian function were assessed by histology, measurement of granulosa cell secretions, and by mating studies.
Mice with GVHD had lower levels of ovarian function and low levels of fertility by mating studies regardless of conditioning regimen. Fertility, however, was preserved in animals who received GVHD prophylaxis. Outcomes were not dependent on the conditioning regimen.
This is a mouse study and may not necessarily translate to humans. The mice in this study also only received conditioning and did not receive the chemotherapy that precedes HSCT in humans with malignancies.