Children Born After Assisted Reproduction More Commonly Carry a Mitochondrial Genotype Associating with Low Birthweight

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Feb 9

PMID 38336715

Authors

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 Barbe

Hubert J M Smeets

Hilde Van de Velde

Karen Sermon

Christophe Blockeel

Claudia Spits

Affiliations

Soon will be listed here.

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.

Citing Articles

The interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes.

Van Der Kelen A, Li Piani L, Mertens J, Regin M, Couvreu de Deckersberg E, Van de Velde H Hum Reprod Open. 2025; 2025(1):hoae074.

PMID: 39830711 PMC: 11739621. DOI: 10.1093/hropen/hoae074.

Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age.

Arbeithuber B, Anthony K, Higgins B, Oppelt P, Shebl O, Tiemann-Boege I bioRxiv. 2024; .

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