title: Immature cryopreserved ovary restores puberty and fertility in mice without alteration of epigenetic marks.
abstract: BACKGROUND
  Progress in oncology could improve survival rate in children, but would probably lead to impaired fertility and puberty. In pre-pubertal girls, the only therapeutic option is the cryopreservation of one ovary. Three births have been reported after reimplantation of cryopreserved mature ovary. Conversely, reimplantation of ovary preserved before puberty (defined as immature ovary) has never been performed in humans.
  
  
  RESULTS
  In order to analyze ovarian function, we performed transplantation using fresh or cryopreserved immature grafts in pre-pubertal or adult mice. Puberty as well as cyclic hormonal activity was restored. All follicle populations were present although a significant reduction in follicle density was observed with or without cryopreservation. Although fertility was restored, the graft is of limited life span. Because ex vivo ovary manipulation and cryopreservation procedure, the status of genomic imprinting was investigated. Methylation status of the H19 and Lit1 Imprinting Control Regions in kidney, muscle and tongue of offsprings from grafted mice does not show significant alteration when compared to those of unoperated mice.
  
  
  CONCLUSIONS
  These results demonstrate that immature ovarian grafting can restore spontaneous puberty and fertility. However, these data suggest that follicle depletion leads to premature ovarian failure. This study addresses the very important epigenetics issue, and provides valuable information to the study of ovarian transplantation suggesting that these procedures do not perturb normal epigenetics marks. These results are highly relevant to the reimplantation question of immature cortex in women.
authors.affiliation: Inserm, Unit 845, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Sauvat
authors.forename: Carmen
authors.initials: C
authors.lastname: Capito
authors.forename: Sabine
authors.initials: S
authors.lastname: Sarnacki
authors.forename: Catherine
authors.initials: C
authors.lastname: Poirot
authors.forename: Anne
authors.initials: A
authors.lastname: Bachelot
authors.forename: Geri
authors.initials: G
authors.lastname: Meduri
authors.forename: Luisa
authors.initials: L
authors.lastname: Dandolo
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
mesh_terms: D000818:Animals; D015925:Cryopreservation / Q000379:methods*; D044127:Epigenesis, Genetic; D005260:Female; D005298:Fertility; D008321:Mammary Glands, Animal / Q000473:pathology; D008745:Methylation; D051379:Mice; D006080:Ovarian Follicle / Q000473:pathology; D010053:Ovary / Q000473:pathology* / Q000502:physiology* / Q000637:transplantation; D012099:Reproductive Techniques; D012741:Sexual Maturation; D013997:Time Factors; D014599:Uterus / Q000473:pathology