Assisted reproductive technologies induce temporally specific placental defects and the preeclampsia risk marker sFLT1 in mouse.

Autor: Vrooman LA; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Rhon-Calderon EA; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Chao OY; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Nguyen DK; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Narapareddy L; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Family and Community Health, Claire M. Fagin School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA., Dahiya AK; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Putt ME; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Schultz RM; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA., Bartolomei MS; Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA bartolom@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Development (Cambridge, England) [Development] 2020 May 29; Vol. 147 (11). Date of Electronic Publication: 2020 May 29.
DOI: 10.1242/dev.186551
Abstrakt: Although widely used, assisted reproductive technologies (ARTs) are associated with adverse perinatal outcomes. To elucidate their underlying causes, we have conducted a longitudinal analysis of placental development and fetal growth using a mouse model to investigate the effects of individual ART procedures: hormone stimulation, in vitro fertilization (IVF), embryo culture and embryo transfer. We demonstrate that transfer of blastocysts naturally conceived without hormone stimulation and developed in vivo prior to transfer can impair early placentation and fetal growth, but this effect normalizes by term. In contrast, embryos cultured in vitro before transfer do not exhibit this compensation but rather display placental overgrowth, reduced fetal weight, reduced placental DNA methylation and increased levels of sFLT1, an anti-angiogenic protein implicated in causing the maternal symptoms of preeclampsia in humans. Increases in sFLT1 observed in this study suggest that IVF procedures could increase the risk for preeclampsia. Moreover, our results indicate that embryo culture is the major factor contributing to most placental abnormalities and should therefore be targeted for optimization.
Competing Interests: Competing interestsThe authors declare no competing or financial interests.
(© 2020. Published by The Company of Biologists Ltd.)
Databáze: MEDLINE