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

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. Conver...

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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
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creator Sauvat, Frédérique
Capito, Carmen
Sarnacki, Sabine
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Bachelot, Anne
Meduri, Geri
Dandolo, Luisa
Binart, Nadine
description 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.
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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. 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1932-6203
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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
title Immature cryopreserved ovary restores puberty and fertility in mice without alteration of epigenetic marks
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