Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility

Radhia M'kacher; Bruno Colicchio; Valentine Marquet; Claire Borie; Wala Najar; William M Hempel; Leonhard Heidingsfelder; Noufissa Oudrhiri; Mustafa Al Jawhari; Nadège Wilhelm-Murer; Marguerite Miguet; Alain Dieterlen; Georges Deschênes; Anne-Claude Tabet; Steffen Junker; Michael Grynberg; Michael Fenech; Annelise Bennaceur-Griscelli; Philippe Voisin; Patrice Carde; Eric Jeandidier; Catherine Yardin

doi:10.1016/j.fertnstert.2020.07.005

Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility

Radhia M'kacher, Bruno Colicchio, Valentine Marquet, Claire Borie, Wala Najar, William M Hempel, Leonhard Heidingsfelder, Noufissa Oudrhiri, Mustafa Al Jawhari, Nadège Wilhelm-Murer, Marguerite Miguet, Alain Dieterlen, Georges Deschênes, Anne-Claude Tabet, Steffen Junker, Michael Grynberg, Michael Fenech, Annelise Bennaceur-Griscelli, Philippe Voisin, Patrice CardeEric Jeandidier, Catherine Yardin

Department of Biomedicine - Forskning og uddannelse, Vest

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

19 Citations (Scopus)

Abstract

OBJECTIVE: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility.

DESIGN: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively.

SETTING: Academic centers.

PATIENT(S): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age.

INTERVENTION(S): Cytogenetic slides were used to detect chromosomal and telomere aberrations.

MAIN OUTCOME MEASURE(S): Telomere length and telomere aberrations were analyzed after telomere and centromere staining.

RESULT(S): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions.

CONCLUSION(S): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field.

Original language	English
Journal	Fertility and Sterility
Volume	115
Issue	1
Pages (from-to)	164-173
Number of pages	10
ISSN	0015-0282
DOIs	https://doi.org/10.1016/j.fertnstert.2020.07.005
Publication status	Published - Jan 2021

Keywords

Infertility
chromosomal aberrations
excessive telomere shortening
telomere doublets
telomere loss

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10.1016/j.fertnstert.2020.07.005

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M'kacher, R., Colicchio, B., Marquet, V., Borie, C., Najar, W., Hempel, W. M., Heidingsfelder, L., Oudrhiri, N., Al Jawhari, M., Wilhelm-Murer, N., Miguet, M., Dieterlen, A., Deschênes, G., Tabet, A.-C., Junker, S., Grynberg, M., Fenech, M., Bennaceur-Griscelli, A., Voisin, P., ... Yardin, C. (2021). Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility. Fertility and Sterility, 115(1), 164-173. https://doi.org/10.1016/j.fertnstert.2020.07.005

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title = "Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility",

abstract = "OBJECTIVE: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility.DESIGN: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively.SETTING: Academic centers.PATIENT(S): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age.INTERVENTION(S): Cytogenetic slides were used to detect chromosomal and telomere aberrations.MAIN OUTCOME MEASURE(S): Telomere length and telomere aberrations were analyzed after telomere and centromere staining.RESULT(S): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions.CONCLUSION(S): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field.",

keywords = "Infertility, chromosomal aberrations, excessive telomere shortening, telomere doublets, telomere loss",

author = "Radhia M'kacher and Bruno Colicchio and Valentine Marquet and Claire Borie and Wala Najar and Hempel, {William M} and Leonhard Heidingsfelder and Noufissa Oudrhiri and {Al Jawhari}, Mustafa and Nad{\`e}ge Wilhelm-Murer and Marguerite Miguet and Alain Dieterlen and Georges Desch{\^e}nes and Anne-Claude Tabet and Steffen Junker and Michael Grynberg and Michael Fenech and Annelise Bennaceur-Griscelli and Philippe Voisin and Patrice Carde and Eric Jeandidier and Catherine Yardin",

year = "2021",

month = jan,

doi = "10.1016/j.fertnstert.2020.07.005",

language = "English",

volume = "115",

pages = "164--173",

journal = "Fertility and Sterility",

issn = "0015-0282",

publisher = "Elsevier Inc.",

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}

M'kacher, R, Colicchio, B, Marquet, V, Borie, C, Najar, W, Hempel, WM, Heidingsfelder, L, Oudrhiri, N, Al Jawhari, M, Wilhelm-Murer, N, Miguet, M, Dieterlen, A, Deschênes, G, Tabet, A-C, Junker, S, Grynberg, M, Fenech, M, Bennaceur-Griscelli, A, Voisin, P, Carde, P, Jeandidier, E & Yardin, C 2021, 'Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility', Fertility and Sterility, vol. 115, no. 1, pp. 164-173. https://doi.org/10.1016/j.fertnstert.2020.07.005

Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility. / M'kacher, Radhia; Colicchio, Bruno; Marquet, Valentine et al.
In: Fertility and Sterility, Vol. 115, No. 1, 01.2021, p. 164-173.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility

AU - M'kacher, Radhia

AU - Colicchio, Bruno

AU - Marquet, Valentine

AU - Borie, Claire

AU - Najar, Wala

AU - Hempel, William M

AU - Heidingsfelder, Leonhard

AU - Oudrhiri, Noufissa

AU - Al Jawhari, Mustafa

AU - Wilhelm-Murer, Nadège

AU - Miguet, Marguerite

AU - Dieterlen, Alain

AU - Deschênes, Georges

AU - Tabet, Anne-Claude

AU - Junker, Steffen

AU - Grynberg, Michael

AU - Fenech, Michael

AU - Bennaceur-Griscelli, Annelise

AU - Voisin, Philippe

AU - Carde, Patrice

AU - Jeandidier, Eric

AU - Yardin, Catherine

PY - 2021/1

Y1 - 2021/1

N2 - OBJECTIVE: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility.DESIGN: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively.SETTING: Academic centers.PATIENT(S): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age.INTERVENTION(S): Cytogenetic slides were used to detect chromosomal and telomere aberrations.MAIN OUTCOME MEASURE(S): Telomere length and telomere aberrations were analyzed after telomere and centromere staining.RESULT(S): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions.CONCLUSION(S): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field.

AB - OBJECTIVE: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility.DESIGN: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively.SETTING: Academic centers.PATIENT(S): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age.INTERVENTION(S): Cytogenetic slides were used to detect chromosomal and telomere aberrations.MAIN OUTCOME MEASURE(S): Telomere length and telomere aberrations were analyzed after telomere and centromere staining.RESULT(S): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions.CONCLUSION(S): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field.

KW - Infertility

KW - chromosomal aberrations

KW - excessive telomere shortening

KW - telomere doublets

KW - telomere loss

UR - http://www.scopus.com/inward/record.url?scp=85097094692&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2020.07.005

DO - 10.1016/j.fertnstert.2020.07.005

M3 - Journal article

C2 - 33272625

SN - 0015-0282

VL - 115

SP - 164

EP - 173

JO - Fertility and Sterility

JF - Fertility and Sterility

IS - 1

ER -

Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility

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Keywords

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