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Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight

Author

Listed:
  • Joke Mertens

    (Vrije Universiteit Brussel)

  • Florence Belva

    (Center for Medical Genetics, UZ Brussel)

  • Aafke P. A. van Montfoort

    (Maastricht University Medical Center)

  • Marius Regin

    (Vrije Universiteit Brussel)

  • Filippo Zambelli

    (Eugin Group)

  • Sara Seneca

    (Vrije Universiteit Brussel
    Center for Medical Genetics, UZ Brussel)

  • Edouard Couvreu de Deckersberg

    (Vrije Universiteit Brussel)

  • Maryse Bonduelle

    (Center for Medical Genetics, UZ Brussel)

  • Herman Tournaye

    (Brussels IVF, Center for Reproductive Medicine, UZ Brussel
    Vrije Universiteit Brussel)

  • Katrien Stouffs

    (Vrije Universiteit Brussel
    Center for Medical Genetics, UZ Brussel)

  • Kurt Barbé

    (Vrije Universiteit Brussel)

  • Hubert J. M. Smeets

    (Maastricht University
    Maastricht University)

  • Hilde Van de Velde

    (Brussels IVF, Center for Reproductive Medicine, UZ Brussel
    Vrije Universiteit Brussel)

  • Karen Sermon

    (Vrije Universiteit Brussel)

  • Christophe Blockeel

    (Brussels IVF, Center for Reproductive Medicine, UZ Brussel
    University of Zagreb)

  • Claudia Spits

    (Vrije Universiteit Brussel)

Abstract

Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after ovarian stimulation (OS) and find that ART individuals carried a different mtDNA genotype than SC individuals, with more de novo non-synonymous variants. These variants, along with rRNA variants, correlate with lower birthweight percentiles, independent of conception mode. Their higher occurrence in ART individuals stems from de novo mutagenesis associated with maternal aging and OS-induced oocyte cohort size. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.

Suggested Citation

  • Joke Mertens & Florence Belva & Aafke P. A. van Montfoort & Marius Regin & Filippo Zambelli & Sara Seneca & Edouard Couvreu de Deckersberg & Maryse Bonduelle & Herman Tournaye & Katrien Stouffs & Kurt, 2024. "Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45446-1
    DOI: 10.1038/s41467-024-45446-1
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    References listed on IDEAS

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    2. Vikas Pejaver & Jorge Urresti & Jose Lugo-Martinez & Kymberleigh A. Pagel & Guan Ning Lin & Hyun-Jun Nam & Matthew Mort & David N. Cooper & Jonathan Sebat & Lilia M. Iakoucheva & Sean D. Mooney & Pred, 2020. "Inferring the molecular and phenotypic impact of amino acid variants with MutPred2," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    3. Sanjay Sonney & Jeremy Leipzig & Marie T Lott & Shiping Zhang & Vincent Procaccio & Douglas C Wallace & Neal Sondheimer, 2017. "Predicting the pathogenicity of novel variants in mitochondrial tRNA with MitoTIP," PLOS Computational Biology, Public Library of Science, vol. 13(12), pages 1-8, December.
    4. Joerg P. Burgstaller & Thomas Kolbe & Vitezslav Havlicek & Stephanie Hembach & Joanna Poulton & Jaroslav Piálek & Ralf Steinborn & Thomas Rülicke & Gottfried Brem & Nick S. Jones & Iain G. Johnston, 2018. "Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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