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

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 Barbé; Hubert J M Smeets; Hilde Van de Velde; Karen Sermon; Christophe Blockeel; Claudia Spits

doi:10.1038/s41467-024-45446-1

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

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 Barbé, Hubert J M Smeets, Hilde Van de Velde, Karen Sermon, Christophe Blockeel, Claudia Spits^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	1232
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-45446-1
Publication status	Published - 9 Feb 2024

Keywords

Pregnancy
Infant, Newborn
Female
Humans
Infant, Premature
Pregnancy Outcome
Pregnancy, Multiple
Premature Birth/epidemiology
Birth Weight
Mitochondria/genetics
DNA, Mitochondrial/genetics

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Mertens, J., Belva, F., van Montfoort, A. P. A., Regin, M., Zambelli, F., Seneca, S., Couvreu de Deckersberg, E., Bonduelle, M., Tournaye, H., Stouffs, K., Barbé, K., Smeets, H. J. M., Van de Velde, H., Sermon, K., Blockeel, C., & Spits, C. (2024). Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight. Nature Communications, 15(1), Article 1232. https://doi.org/10.1038/s41467-024-45446-1

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title = "Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight",

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.",

keywords = "Pregnancy, Infant, Newborn, Female, Humans, Infant, Premature, Pregnancy Outcome, Pregnancy, Multiple, Premature Birth/epidemiology, Birth Weight, Mitochondria/genetics, DNA, Mitochondrial/genetics",

author = "Joke Mertens and Florence Belva and {van Montfoort}, {Aafke P A} and Marius Regin and Filippo Zambelli and Sara Seneca and {Couvreu de Deckersberg}, Edouard and Maryse Bonduelle and Herman Tournaye and Katrien Stouffs and Kurt Barb{\'e} and Smeets, {Hubert J M} and {Van de Velde}, Hilde and Karen Sermon and Christophe Blockeel and Claudia Spits",

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Mertens, J, Belva, F, van Montfoort, APA, Regin, M, Zambelli, F, Seneca, S, Couvreu de Deckersberg, E, Bonduelle, M, Tournaye, H, Stouffs, K, Barbé, K, Smeets, HJM, Van de Velde, H, Sermon, K, Blockeel, C & Spits, C 2024, 'Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight', Nature Communications, vol. 15, no. 1, 1232. https://doi.org/10.1038/s41467-024-45446-1

TY - JOUR

T1 - Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight

AU - Mertens, Joke

AU - Belva, Florence

AU - van Montfoort, Aafke P A

AU - Regin, Marius

AU - Zambelli, Filippo

AU - Seneca, Sara

AU - Couvreu de Deckersberg, Edouard

AU - Bonduelle, Maryse

AU - Tournaye, Herman

AU - Stouffs, Katrien

AU - Barbé, Kurt

AU - Smeets, Hubert J M

AU - Van de Velde, Hilde

AU - Sermon, Karen

AU - Blockeel, Christophe

AU - Spits, Claudia

PY - 2024/2/9

Y1 - 2024/2/9

N2 - 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.

AB - 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.

KW - Pregnancy

KW - Infant, Newborn

KW - Female

KW - Humans

KW - Infant, Premature

KW - Pregnancy Outcome

KW - Pregnancy, Multiple

KW - Premature Birth/epidemiology

KW - Birth Weight

KW - Mitochondria/genetics

KW - DNA, Mitochondrial/genetics

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DO - 10.1038/s41467-024-45446-1

M3 - Article

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1232

ER -

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

Abstract

Keywords

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