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

Claudia Spits; Joke Mertens; Florence Belva; Aafke PA van Montfoort; Marius Regin; Filippo Zambelli; Sara Seneca; Edouard Couvreu De Deckersberg; Mary-Louise Bonduelle; Herman Tournaye; Katrien Stouffs; Kurt Barbé; Bert Smeets; Hilde Van De Velde; Karen Sermon; Christophe Blockeel

doi:10.1038/s41467-024-45446-1

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

Claudia Spits, Joke Mertens, Florence Belva, Aafke PA van Montfoort, Marius Regin, Filippo Zambelli, Sara Seneca, Edouard Couvreu De Deckersberg, Mary-Louise Bonduelle, Herman Tournaye, Katrien Stouffs, Kurt Barbé, Bert Smeets, Hilde Van De Velde, Karen Sermon, Christophe Blockeel

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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
Pages (from-to)	1232
Number of pages	16
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-45446-1
Publication status	Published - 9 Feb 2024

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Publisher Copyright:
© 2024. The Author(s).

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108410130Final published version, 2.13 MBLicence: CC BY

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Spits, C., Mertens, J., Belva, F., van Montfoort, A. PA., Regin, M., Zambelli, F., Seneca, S., Couvreu De Deckersberg, E., Bonduelle, M.-L., Tournaye, H., Stouffs, K., Barbé, K., Smeets, B., Van De Velde, H., Sermon, K., & Blockeel, C. (2024). Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight. Nature Communications, 15(1), 1232. 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.",

author = "Claudia Spits and Joke Mertens and Florence Belva and {van Montfoort}, {Aafke PA} and Marius Regin and Filippo Zambelli and Sara Seneca and {Couvreu De Deckersberg}, Edouard and Mary-Louise Bonduelle and Herman Tournaye and Katrien Stouffs and Kurt Barb{\'e} and Bert Smeets and {Van De Velde}, Hilde and Karen Sermon and Christophe Blockeel",

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

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AU - Spits, Claudia

AU - Mertens, Joke

AU - Belva, Florence

AU - van Montfoort, Aafke PA

AU - Regin, Marius

AU - Zambelli, Filippo

AU - Seneca, Sara

AU - Couvreu De Deckersberg, Edouard

AU - Bonduelle, Mary-Louise

AU - Tournaye, Herman

AU - Stouffs, Katrien

AU - Barbé, Kurt

AU - Smeets, Bert

AU - Van De Velde, Hilde

AU - Sermon, Karen

AU - Blockeel, Christophe

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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.

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

Abstract

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