Year: 2023
Type: article
Study design: Observational Study
Abstract: Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extra-embryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extra-embryonic mesoderm rather than chorionic villi. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.
Source: Nature Medicine
Authors: Rick Essers, Igor N. Lebedev, Ants Kurg, Elizaveta A. Fonova, Servi J. C. Stevens, Rebekka M. Koeck, Ulrike von Rango, Lloyd Brandts, Spyridon Panagiotis Deligiannis, Tatyana V. Nikitina, Elena A. Sazhenova, Ekaterina N. Tolmacheva, Anna A. Kashevarova, Dmitry A. Fedotov, Viktoria V. Demeneva, Daria I. Zhigalina, Gleb V. Drozdov, Salwan Al-Nasiry, Merryn V. E. Macville, Arthur van den Wijngaard, Jos Dreesen, Aimee Paulussen, Alexander Hoischen, Han G. Brunner, Andres Salumets, Masoud Zamani Esteki
Institutions: Maastricht University Medical Centre, Maastricht University, Russian Academy of Sciences, Research Institute of Medical Genetics of Russian Academy of Medical Sciences, Tomsk National Research Medical Center, University of Tartu, University of Helsinki, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Karolinska University Hospital, Karolinska Institutet, Competence Centre on Health Technologies (Estonia)
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Awards: G1039623668, G1103610791, The role of endometrium as a major factor affecting female fertility and pregnancy outcome, G434337789, G6629816786, G7889934125, CROSS-SECTORAL ALLIANCE AS THE KEY FOR INNOVATION-DRIVEN BUSINESS SUCCESS OF ESTONIAN AND GREEK REPRODUCTIVE HEALTHCARE, Ethically Responsible INnovations in reproductive medicine
OpenAlex ID: W4388939307