Immature cryopreserved ovary restores puberty and fertility in mice without alteration of epigenetic marks

• Published in: PloS one 2008-04, Vol.3 (4), p.e1972-e1972
• Main Authors: Sauvat, Frédérique, Capito, Carmen, Sarnacki, Sabine, Poirot, Catherine, Bachelot, Anne, Meduri, Geri, Dandolo, Luisa, Binart, Nadine
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biopsy; Births; Cancer; Children; Chromosomes; Cryopreservation; Cryopreservation - methods; Diabetes and Endocrinology/Reproductive Endocrinology; DNA methylation; Drug dosages; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Female; Fertility; Genes; Genetic engineering; Genetics and Genomics/Epigenetics; Genomic imprinting; Girls; Grafting; Grafts; Health aspects; Imprinting; Infertility; Laparoscopy; Life span; Mammary Glands, Animal - pathology; Medicine; Methylation; Mice; Organ transplantation; Ovarian Follicle - pathology; Ovary - pathology; Ovary - physiology; Ovary - transplantation; Pediatrics; Pediatrics and Child Health/Pediatric Oncology; Physiology/Endocrinology; Pregnancy; Puberty; Reproductive status; Reproductive Techniques; Reproductive technologies; Sexual Maturation; Survival; Time Factors; Tongue; Transplantation; Transplants & implants; Uterus - pathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001972

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. 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. 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.