Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model
Open accessAbstract
OBJECTIVE: To study the impact of aneuploid granulosa and stromal cells on folliculogenesis of small ovarian follicles from patients with mosaic Turner syndrome (TS) using a murine xenograft model. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S): Ovarian cortical tissue was obtained by laparoscopic surgery from 18 patients with mosaic TS (aged 5-19 years) and 13 controls (aged 5-18 years). INTERVENTION(S): Part of each tissue fragment was used to karyotype ovarian cells in nongrafted tissue by fluorescence in situ hybridization. The remaining tissue was xenografted to severe combined immunodeficient mice for 5 months. Grafted tissue was analyzed for aneuploidy, and follicle density and morphology were determined. Expressions of proliferating cell nuclear antigen and anti-Müllerian hormone were investigated by immunohistochemistry. MAIN OUTCOME MEASURE(S): The impact of aneuploid granulosa and stromal cells on folliculogenesis. Fluorescence in situ hybridization of ovarian tissue before grafting was performed to determine the level of aneuploidy in stromal cells and oocytes and granulosa of small follicles. After xenografting, the level of aneuploidy of the newly formed layers of granulosa cells was again determined in secondary and antral follicles. RESULT(S): Follicle density in ovarian tissue from patients with TS was significantly lower than in controls before grafting. Fluorescence in situ hybridization analysis confirmed that 101 of 104 oocytes from nongrafted tissue of patients with TS showed normal X chromosome content, whereas granulosa and stromal cells were mainly 45,X. Fragments from 12 patients with TS contained follicles at all stages after xenografting, including secondary and antral follicles. Follicle density in patients with TS and controls decreased significantly after grafting. Moreover, a shift from high to low proportions of 45,X granulosa cells was observed during folliculogenesis. Expression of proliferating cell nuclear antigen in follicles from patients with TS increased significantly during grafting. Secretion of anti-Müllerian hormone was impaired before grafting in peripubertal/postpubertal girls with TS, but recovered after grafting. CONCLUSION(S): Our study showed that small follicles from patients with mosaic TS undergoes folliculogenesis, despite the presence of aneuploid granulosa and stromal cells. Ovarian tissue cryopreservation could therefore be a valid option to preserve fertility in young patients with mosaic TS if sufficient numbers of follicles are present, thus preferably before the age of 12.
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Those with monosomy X could still be fertile enough to undergo ovarian stimulation successfully or become pregnant spontaneously, as a wide variation is seen between karyotype in peripheral cells and ovarian cells.
“It is important to keep in mind that those with monosomy X could still be fertile enough to undergo ovarian stimulation successfully or become pregnant spontaneously, as a wide variation is seen between karyotype in peripheral cells and ovarian cells.576,609,610”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [609]
Despite the presence of a large content of aneuploid granulosa and stromal cells, primordial follicles underwent normal follicular development until antral stages.
“Despite the presence of a large content of aneuploid granulosa and stromal cells, primordial follicles underwent normal follicular development until antral stages.”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [609]
Aberrant follicle morphology of up to 30%-67% was observed in TS ovaries.
“Additionally, an aberrant follicle morphology of up to 30%-67% was observed in TS ovaries.579,609”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [609]
Prepubertal girls with mosaic TS could have a more promising outcome after ovarian tissue transplantation (OTT) than pubertal girls.
“This supports the theory that prepubertal girls with mosaic TS could have a more promising outcome after ovarian tissue transplantation (OTT) than pubertal girls.609”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [609]
The follicle density of xenografts from ovaries of prepubertal girls with TS was significantly higher than that of pubertal girls with TS and was comparable to that of age-matched controls.
“The follicle density of xenografts from ovaries of prepubertal girls with TS was significantly higher than that of pubertal girls with TS and was comparable to that of age-matched controls.”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [609]
In vitro studies in mosaic girls showed most oocytes had a normal X chromosomal content, while granulosa and ovarian stromal cells were mainly aneuploid.
“However, in vitro studies in mosaic girls have been encouraging. They showed that most oocytes had a normal X chromosomal content, while granulosa and ovarian stromal cells were mainly aneuploid.575,600,608-610”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [609]
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Cites
Livebirth after orthotopic transplantation of cryopreserved ovarian tissue
Donnez, J., Dolmans, M., Demylle, D., Jadoul, P., Pirard, C., Squifflet, J. P., Martínez-Madrid, B., & Langendonckt, A. V. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17222-x · Cited by 1,634 · see citing works
Self-citationDevelopment of Follicles in the Mammalian Ovary
Hirshfield, A. N. (1991) · International review of cytology · doi:10.1016/s0074-7696(08)61524-7 · Cited by 1,281 · see citing works
Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment
Kawamura, K., Cheng, Y., Suzuki, N., Deguchi, M., Sato, Y., Takae, S., Ho, C.-H., Kawamura, N., Tamura, M., Hashimoto, S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312830110 · Cited by 868 · see citing works
Silencing of unsynapsed meiotic chromosomes in the mouse
Turner, J. M. A., Mahadevaiah, S. K., Fernández-Capetillo, Ó., Nussenzweig, A., Xu, X., Deng, C., & Burgoyne, P. S. (2004) · Nature Genetics · doi:10.1038/ng1484 · Cited by 550 · see citing works
Regulation of primordial follicle assembly and development
Skinner, M. K. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi020 · Cited by 523 · see citing works
Dolmans, M., Marinescu, C., Saussoy, P., Langendonckt, A. V., Amorim, C. A., & Donnez, J. (2010) · Blood · doi:10.1182/blood-2010-01-265751 · Cited by 441 · see citing works
Self-citationThe consequences of asynapsis for mammalian meiosis
Burgoyne, P. S., Mahadevaiah, S. K., & Turner, J. M. A. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2505 · Cited by 367 · see citing works
Ranke, M. B., & Saenger, P. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05487-3 · Cited by 345 · see citing works
Dolmans, M., von Wolff, M., Poirot, C., Díaz‐García, C., Cacciottola, L., Boissel, N., Liebenthron, J., Pellicer, A., Donnez, J., & Andersen, C. Y. (2021) · Fertility and Sterility · doi:10.1016/j.fertnstert.2021.03.008 · Cited by 341 · see citing works
Self-citationJensen, A. K., Macklon, K. T., Fedder, J., et al. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0843-9 · Cited by 275 · see citing works
Birgit, B., Julius, H., Carsten, R., Maryam, S., Gabriel, F., Victoria, K., Margareta, F., & Outi, H. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0708 · Cited by 254 · see citing works
Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads
Modi, D. N. (2003) · Molecular Human Reproduction · doi:10.1093/molehr/gag031 · Cited by 253 · see citing works
Epidemiological, endocrine and metabolic features in Turner syndrome
Gravholt, C. H. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1510657 · Cited by 248 · see citing works
Awakening the oocyte: controlling primordial follicle development
McLaughlin, E. A., & McIver, S. C. (2008) · Reproduction · doi:10.1530/rep-08-0118 · Cited by 211 · see citing works
The Role of the Extracellular Matrix in Ovarian Follicle Development
Woodruff, T. K., & Shea, L. D. (2007) · Reproductive Sciences · doi:10.1177/1933719107309818 · Cited by 208 · see citing works
Follicles Are Found in the Ovaries of Adolescent Girls with Turner's Syndrome
Hreinsson, J. G., Otala, M., Fridström, M., Borgström, B., Rasmussen, C., Lundqvist, M., Tuuri, T., Simberg, N. H., Mikkola, M., Dunkel, L., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8753 · Cited by 192 · see citing works
Turner syndrome: four challenges across the lifespan
Sutton, E. J., McInerney‐Leo, A., Bondy, C. A., Gollust, S. E., King, D., & Biesecker, B. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30911 · Cited by 171 · see citing works
Number of ovarian follicles in human fetuses with the 45,x karyotype
Reynaud, K., Cortvrindt, R. G., Verlinde, F., Schepper, J. D., Bourgain, C., & Smitz, J. E. J. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.12.011 · Cited by 146 · see citing works
The pseudoautosomal regions, SHOX and disease
Blaschke, R. J., & Rappold, G. (2006) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.04.004 · Cited by 135 · see citing works
Fertility Preservation in Women
van den Heuvel‐Eibrink, M. M., van der Kooi, A.-L. L. F., & Wallace, W. H. (2018) · New England Journal of Medicine · doi:10.1056/nejmc1715731 · Cited by 105 · see citing works
Morphologic and functional determinants of primordial and primary follicles in the monkey ovary
Gougeon, A., & Busso, D. (2000) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(00)00220-3 · Cited by 93 · see citing works
Mamsen, L. S., Charkiewicz, K., Anderson, R. A., Telfer, E. E., McLaughlin, M., Kelsey, T. W., Kristensen, S. G., Gook, D. A., Ernst, E., & Andersen, C. Y. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.02.003 · Cited by 86 · see citing works
Role of the PI3K and Hippo pathways in follicle activation after grafting of human ovarian tissue
Masciangelo, R., Hossay, C., Chiti, M. C., et al. (2019) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-019-01628-1 · Cited by 70 · see citing works
Cacciottola, L., Manavella, D. D., Amorim, C. A., et al. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.04.009 · Cited by 67 · see citing works
Peek, R., Schleedoorn, M., Smeets, D., van de Zande, G., Groenman, F., Braat, D., van der Velden, J., & Fleischer, K. (2019) · Human Reproduction · doi:10.1093/humrep/dez135 · Cited by 67 · see citing works
Self-citationLuyckx, V., Scalercio, S. R. R. D. A., Jadoul, P., Amorim, C. A., Soares, M. P. M., Donnez, J., & Dolmans, M. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.07.202 · Cited by 63 · see citing works
Self-citationDavid, A., Langendonckt, A. V., Gilliaux, S., Dolmans, M., Donnez, J., & Amorim, C. A. (2012) · Human Reproduction · doi:10.1093/humrep/des013 · Cited by 60 · see citing works
Self-citationOvarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes
Cacciottola, L., Donnez, J., & Dolmans, M. (2021) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2021.06.019 · Cited by 45 · see citing works
Self-citationLambalk, C. B. (2004) · Human Reproduction · doi:10.1093/humrep/deh216 · Cited by 42 · see citing works
Viuff, M., & Gravholt, C. H. (2022) · Annales d Endocrinologie · doi:10.1016/j.ando.2022.06.001 · Cited by 36 · see citing works
Nadesapillai, S., van der Velden, J., Smeets, D., van de Zande, G., Braat, D., Fleischer, K., & Peek, R. (2021) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.11.006 · Cited by 31 · see citing works
Self-citationTo Freeze or Not to Freeze? An Update on Fertility Preservation In Females with Turner Syndrome.
Schleedoorn, M., van der Velden, J. A. E. M., Braat, D. D. M., Peek, R., & Fleischer, K. (2019) · PubMed · doi:10.17458/per.vol16.2019.svb.tofreezeornot · Cited by 21 · see citing works
Self-citationWhy Turner patients with 45, X monosomy should not be excluded from fertility preservation services
Schleedoorn, M., Fleischer, K., Braat, D., Oerlemans, A., van der Velden, A., & Peek, R. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-01015-z · Cited by 20 · see citing works
Self-citationNielsen, J., & Krag-Olsen, B. (1980) · Human Genetics · doi:10.1007/bf00290218 · Cited by 19 · see citing works
Gupta, S., Chiplunkar, S., Gupta, A., et al. (2003) · Genes and Immunity · doi:10.1038/sj.gene.6363945 · Cited by 14 · see citing works
Turner syndrome: fertility counselling in childhood and through the reproductive lifespan
Bollig, K. J., Mainigi, M. A., Senapati, S., Lin, A. E., Levitsky, L. L., & Bamba, V. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000784 · Cited by 13 · see citing works
Life with Turnerʼs Syndrome—A Psychosocial Report From 22 Middle-Aged Women
Sylvén, L., Magnusson, C., Hagenfeldt, K., & von Schoultz, B. (1994) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-199404000-00019 · Cited by 9 · see citing works
Optimizing the outcomes of ovarian tissue transplantation
Nisolle, M., Brichant, G., & Henry, L. (2020) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.11.022 · Cited by 3 · see citing works
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Clinical practice guidelines for the care of girls and women with Turner syndrome.
Gravholt, C. H., Andersen, N. H., Christin-Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel-Guerra, A. T., Gutmark-Little, I., Fleischer, K., Hong, D., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae050 · Cited by 224 · see citing works
Self-citationNadesapillai, S., van der Velden, J., van der Coelen, S., Schleedoorn, M., Sedney, A., Spath, M., Schurink, M., Oerlemans, A., IntHout, J., Beerendonk, I., et al. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.08.004 · Cited by 38 · see citing works
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- Authors
- Peek, R., Nadesapillai, S., Thi Nguyen, T. Y., Vassart, S., Smeets, D., van de Zande, G., Camboni, A., Braat, D., van der Velden, J., Donnez, J., Fleischer, K., & Dolmans, M.-M.
- Affiliations
- Radboud University Medical Center (NL)
- UCLouvain (BE)
- Cliniques Universitaires Saint-Luc (BE)
- Corresponding author
- Dolmans, Marie-Madeleine
- ORCID
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2023-08
- Volume
- 120
- Issue
- 2
- Pages
- 371-381
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W4365452241
- Cited by
- 30
- References
- 38
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 9 · 2023: 4
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion, cc-by)
- SSRN Electronic Journal (acceptedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Foundation Against Cancer (2018-042)
- Saint-Luc Foundation
- Merck Pharmaceuticals (A16-1395)
- Fondation contre le Cancer
- EMD Serono
- Fonds national suisse de la recherche scientifique
- Fonds De La Recherche Scientifique - FNRS (30443682, 5/4/150/5)
- Ferring Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- Turner syndrome, mosaic Turner syndrome, folliculogenesis, granulosa cells, stromal cells, 45,X, follicle density, anti-Müllerian hormone, proliferating cell nuclear antigen, oocyte aneuploidy, ovarian reserve, peripubertal girls, antral follicles
- MeSH terms
- Aneuploidy, Animals, Female, Humans, Turner Syndrome, In Situ Hybridization, Fluorescence, Proliferating Cell Nuclear Antigen, Mice, Anti-Mullerian Hormone, Heterografts
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