Graft-versus-host disease targets ovary and causes female infertility in mice.
Sonoko ShimojiDaigo HashimotoHidetsugu TsujigiwaKohta MiyawakiKoji KatoShuichiro TakahashiReiki OgasawaraTakashi JiromaruHiromi IwasakiToshihiro MiyamotoKoichi AkashiTakanori TeshimaPublished in: Blood (2016)
Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). Although pretransplant conditioning regimen has been appreciated as a cause of ovarian failure, increased application of reduced-intensity conditioning allowed us to revisit other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell-mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice. Histological evaluation of the ovaries after SCT demonstrated donor T-cell infiltration in close proximity to apoptotic granulosa cells in the ovarian follicles, resulting in impaired follicular hormone production and maturation of ovarian follicles. Mating experiments showed that female recipients of allogeneic SCT deliver significantly fewer newborns than recipients of syngeneic SCT. GVHD-mediated ovary insufficiency and infertility were independent of conditioning. Pharmacologic GVHD prophylaxis protected the ovary from GVHD and preserved fertility. These results demonstrate for the first time that GVHD targets the ovary and impairs ovarian function and fertility and has important clinical implications in young female transplant recipients with nonmalignant diseases, in whom minimally toxic regimens are used.
Keyphrases
- allogeneic hematopoietic stem cell transplantation
- acute myeloid leukemia
- acute lymphoblastic leukemia
- polycystic ovary syndrome
- stem cell transplantation
- pregnant women
- induced apoptosis
- type diabetes
- high fat diet induced
- young adults
- insulin resistance
- signaling pathway
- adipose tissue
- cell cycle arrest
- high intensity
- preterm infants
- endoplasmic reticulum stress
- gestational age