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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

Array-CGH diagnosis in ovarian failure: identification of new molecular actors for ovarian physiology

Authors: Sylvie Jaillard, Linda Akloul, Marion Beaumont, Houda Hamdi-Roze, Christele Dubourg, Sylvie Odent, Solène Duros, Nathalie Dejucq-Rainsford, Marc-Antoine Belaud-Rotureau, Célia Ravel

Published in: Journal of Ovarian Research | Issue 1/2016

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Abstract

Background

Ovarian failure (OF) is considered premature if it occurs before the age of 40.
This study investigates the genetic aetiology underlying OF in women under the age of 40 years.

Methods

We conducted an experimental prospective study performing all genome microarrays in 60 patients younger than 40 years presenting an OF revealed by a decrease of circulating Anti-Müllerian Hormone (AMH) and leading to an oocyte donation program.

Results

We identified nine significant copy number variations (CNVs) including candidate genes potentially implicated in reproductive function. These genes are principally involved in cell division and chromosome segregation (SYCE1, CLASP1, CENP-A, CDC16), in ciliary development and/or function (RSPH1, KIF24), are linked with known gonadal genes or expressed in female genital tract (CSMD1, SEMA6D, KIAA1324).

Conclusions

Our data strengthen the idea that microarrays should be used in combination with karyotype for aetiological assessment of patients with OF. This analysis may have a therapeutic impact as the identification of new molecular actors for gonadal development or ovarian physiology is useful for the prediction of an ovarian reserve decline and makes possible preventive fertility preservation.
Literature
1.
Ravel C, Kazdar N, Leveque J. Ovarian failure: new treatments in perspective? Gynecol Obstet Fertil. 2016;44:56–62.CrossRefPubMed
2.
Gleicher N, Kim A, Kushnir V, Weghofer A, Shohat-Tal A, Lazzaroni E, Lee HJ, Barad DH. Clinical relevance of combined FSH and AMH observations in infertile women. J Clin Endocrinol Metab. 2013;98:2136–45.CrossRefPubMed
3.
Van Disseldorp J, Faddy MJ, Themmen AP, de Jong FH, Peeters PH, van der Schouw YT, Broekmans FJ. Relationship of serum antimüllerian hormone concentration to age at menopause. J Clin Endocrinol Metab. 2008;93:2129–34.CrossRefPubMed
4.
Broer SL, Eijkemans MJ, Scheffer GJ, van Rooij IA, de Vet A, Themmen AP, Laven JS, de Jong FH, Te Velde ER, Fauser BC, Broekmans FJ. Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women. J Clin Endocrinol Metab. 2011;96:2532–9.CrossRefPubMed
5.
Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder--a plea for universal definitions. J Assist Reprod Genet. 2015;32:1709–12.CrossRefPubMed
6.
Bashamboo A, Ravel C, Brauner R, McElreavey K. NR5A1 and ovarian failure. Med Sci (Paris). 2009;25(10):809–13.CrossRef
7.
Wood MA, Rajkovic A. Genomic markers of ovarian reserve. Semin Reprod Med. 2013;6:399–415.CrossRef
8.
Ledig S, Hiort O, Scherer G, Hoffmann M, Wolff G, Morlot S, Kuechler A, Wieacker P. Array-CGH analysis in patients with syndromic and non-syndromic XY gonadal dysgenesis: evaluation of array CGH as diagnostic tool and search for new candidate loci. Hum Reprod. 2010;10:2637–46.CrossRef
9.
Baronchelli S, Villa N, Redaelli S, Lissoni S, Saccheri F, Panzeri E, Conconi D, Bentivegna A, Crosti F, Sala E, Bertola F, Marozzi A, Pedicini A, Ventruto M, Police MA, Dalprà L. Investigating the role of X chromosome breakpoints in premature ovarian failure. Mol Cytogenet. 2012;5:32.CrossRefPubMedPubMedCentral
10.
Fonseca DJ, Patiño LC, Suárez YC, de Jesús Rodríguez A, Mateus HE, Jiménez KM, Ortega-Recalde O, Díaz-Yamal I, Laissue P. Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations. Fertil Steril. 2015;104:154–62.CrossRefPubMed
11.
White S, Ohnesorg T, Notini A, Roeszler K, Hewitt J, Daggag H, Smith C, Turbitt E, Gustin S, van den Bergen J, Miles D, Western P, Arboleda V, Schumacher V, Gordon L, Bell K, Bengtsson H, Speed T, Hutson J, Warne G, Harley V, Koopman P, Vilain E, Sinclair A. Copy number variation in patients with disorders of sex development due to 46,XY gonadal dysgenesis. PLoS One. 2011;6:e17793.CrossRefPubMedPubMedCentral
12.
Dutrillaux B, et Couturier J. La pratique de l’analyse chromosomique. Paris: Masson; 1981.
13.
Muleris M, Richard F, Apiou F, Dutrillaux B. Hybridation in situ en cytogénétique moléculaire. Paris: Lavoisier; 1996.
14.
McGuire MM, Bowden W, Engel NJ, Ahn HW, Kovanci E, Rajkovic A. Genomic analysis using high-resolution single-nucleotide polymorphism arrays reveals novel microdeletions associated with premature ovarian failure. Fertil Steril. 2011;95:1595–600.CrossRefPubMedPubMedCentral
15.
Aboura A, Dupas C, Tachdjian G, Portnoï MF, Bourcigaux N, Dewailly D, Frydman R, Fauser B, Ronci-Chaix N, Donadille B, Bouchard P, Christin-Maitre S. Array comparative genomic hybridization profiling analysis reveals deoxyribonucleic acid copy number variations associated with premature ovarian failure. J Clin Endocrinol Metab. 2009;94:4540–6.CrossRefPubMed
16.
Ledig S, Röpke A, Wieacker P. Copy number variants in premature ovarian failure and ovarian dysgenesis. Sex Dev. 2010;4:225–32.CrossRefPubMed
17.
Norling A, Hirschberg AL, Rodriguez-Wallberg KA, Iwarsson E, Wedell A, Barbaro M. Identification of a duplication within the GDF9 gene and novel candidate genes for primary ovarian insufficiency (POI) by a customized high-resolution array comparative genomic hybridization platform. Hum Reprod. 2014;29:1818–27.CrossRefPubMedPubMedCentral
18.
Kraus DM, Elliott GS, Chute H, Horan T, Pfenninger KH, Sanford SD, Foster S, Scully S, Welcher AA, Holers VM. CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues. J Immunol. 2006;176:4419–30.CrossRefPubMed
19.
Cukier HN, Dueker ND, Slifer SH, Lee JM, Whitehead PL, Lalanne E, Leyva N, Konidari I, Gentry RC, Hulme WF, Booven DV, Mayo V, Hofmann NK, Schmidt MA, Martin ER, Haines JL, Cuccaro ML, Gilbert JR, Pericak-Vance MA. Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders. Mol Autism. 2014;5:1.CrossRefPubMedPubMedCentral
20.
Kuusisto KM, Akinrinade O, Vihinen M, Kankuri-Tammilehto M, Laasanen SL, Schleutker J. Copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer. PLoS One. 2013;8:e71802.CrossRefPubMedPubMedCentral
21.
de Vries L, Behar DM, Smirin-Yosef P, Lagovsky I, Tzur S, Basel-Vanagaite L. Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency. J Clin Endocrinol Metab. 2014;99:E2129–32.CrossRefPubMed
22.
Maiato H, Fairley EA, Rieder CL, Swedlow JR, Sunkel CE, Earnshaw WC. Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics. Cell. 2003;113:891–904.CrossRefPubMed
23.
Manning AL, Bakhoum SF, Maffini S, Correia-Melo C, Maiato H, Compton DA. CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore-microtubule dynamics to promote mitotic progression and fidelity. EMBO J. 2010;29:3531–43.CrossRefPubMedPubMedCentral
24.
25.
Wang J, Dye BT, Rajashankar KR, Kurinov I, Schulman BA. Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure. Nat Struct Mol Biol. 2009;16:987–9.CrossRefPubMedPubMedCentral
26.
Kittler R, Putz G, Pelletier L, Poser I, Heninger AK, Drechsel D, Fischer S, Konstantinova I, Habermann B, Grabner H, Yaspo ML, Himmelbauer H, Korn B, Neugebauer K, Pisabarro MT, Buchholz F. An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature. 2004;432:1036–40.CrossRefPubMed
27.
Klinger FG, Rossi V, De Felici M. Multifaceted programmed cell death in the mammalian fetal ovary. Int J Dev Biol. 2015;59:51–4.CrossRefPubMed
28.
29.
Baker MD, Ezzati M, Aloisio GM, Tarnawa ED, Cuevas I, Nakada Y, Castrillon DH. The small GTPase Rheb is required for spermatogenesis but not oogenesis. Reproduction. 2014;147:615–25.CrossRefPubMedPubMedCentral
30.
Howman EV, Fowler KJ, Newson AJ, Redward S, MacDonald AC, Kalitsis P, Choo KH. Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc Natl Acad Sci U S A. 2000;97:1148–53.CrossRefPubMedPubMedCentral
31.
Knowles MR, Ostrowski LE, Leigh MW, Sears PR, Davis SD, Wolf WE, Hazucha MJ, Carson JL, Olivier KN, Sagel SD, Rosenfeld M, Ferkol TW, Dell SD, Milla CE, Randell SH, Yin W, Sannuti A, Metjian HM, Noone PG, Noone PJ, Olson CA, Patrone MV, Dang H, Lee HS, Hurd TW, Gee HY, Otto EA, Halbritter J, Kohl S, Kircher M, Krischer J, Bamshad MJ, Nickerson DA, Hildebrandt F, Shendure J, Zariwala MA. Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype. Am J Respir Crit Care Med. 2014;189:707–17.CrossRefPubMedPubMedCentral
32.
Kobayashi T, Tsang WY, Li J, Lane W, Dynlacht BD. Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis. Cell. 2011;145:914–25.CrossRefPubMed
33.
34.
35.
Pisarska MD, Kuo FT, Tang D, Zarrini P, Khan S, Ketefian A. Expression of forkhead transcription factors in human granulosa cells. Fertil Steril. 2009;91:1392–4.CrossRefPubMed
36.
Schlumbrecht MP, Xie SS, Shipley GL, Urbauer DL, Broaddus RR. Molecular clustering based on ERα and EIG121 predicts survival in high-grade serous carcinoma of the ovary/peritoneum. Mod Pathol. 2011;24:453–62.CrossRefPubMed
37.
Jaillard S, Bashamboo A, Pasquier L, Belaud-Rotureau MA, McElreavey K, Odent S, Ravel C. Gene dosage effects in 46, XY DSD: usefulness of CGH technologies for diagnosis. J Assist Reprod Genet. 2015;32:287–91.CrossRefPubMed
38.
Eggers S, Smith KR, Bahlo M, Looijenga LH, Drop SL, Juniarto ZA, Harley VR, Koopman P, Faradz SM, Sinclair AH. Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1. Eur J Hum Genet. 2015;23:486–93.CrossRefPubMed
39.
Laissue P. Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing. Mol Cell Endocrinol. 2015;411:243–57.CrossRefPubMed
Metadata
Title
Array-CGH diagnosis in ovarian failure: identification of new molecular actors for ovarian physiology
Authors
Sylvie Jaillard
Linda Akloul
Marion Beaumont
Houda Hamdi-Roze
Christele Dubourg
Sylvie Odent
Solène Duros
Nathalie Dejucq-Rainsford
Marc-Antoine Belaud-Rotureau
Célia Ravel
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-016-0272-5

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