Research Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Center for Medical Genetics, UZ Brussel, Brussels, Belgium.
Nat Commun. 2024 Feb 9;15(1):1232. doi: 10.1038/s41467-024-45446-1.
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.
通过辅助生殖技术（ART）受孕的儿童出生体重较低的风险增加，但潜在原因尚不清楚。我们的研究通过影响产前发育过程中的线粒体功能，探讨线粒体 DNA（mtDNA）变体作为导致出生体重差异的因素。我们对 451 名接受 ART 和自然受孕（SC）的个体、157 对母婴和 113 个来自自然月经周期或卵巢刺激（OS）后的单个卵子进行了 mtDNA 深度测序，发现 ART 个体的 mtDNA 基因型与 SC 个体不同，具有更多的从头非同义变体。这些变体与 rRNA 变体一起，与较低的出生体重百分位相关，与受孕方式无关。它们在 ART 个体中更高的发生率源于与母体衰老和 OS 诱导的卵母细胞群体大小相关的从头突变。未来的研究将确定这些变化的长期健康后果，以及这些发现将如何影响未来的临床实践和患者咨询。
