02117nas a2200265   4500000000100000000000100001008004100002260001100043653001500054653003200069653001600101653001400117653002900131653001600160653002500176653002700201100002400228700002000252245009100272856004600363300000900409490000700418520141200425022001401837       2022                            d  c2022/110aaneuploidy10aextended blastocyst culture10amiscarriage10aMosaicism10arecurrent pregnancy loss10atrophoblast10atrophoblast organoid10atrophoblast stem cells1 aTatiana V. Nikitina1 aIgor N. Lebedev00aStem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages  uhttps://www.mdpi.com/2073-4409/11/12/1923  a19230 v113 aMiscarriage affects approximately 15% of clinically recognized pregnancies, and 1–3% of couples experience pregnancy loss recurrently. Approximately 50–60% of miscarriages result from chromosomal abnormalities, whereas up to 60% of euploid recurrent abortions harbor variants in candidate genes. The growing number of detected genetic variants requires an investigation into their role in adverse pregnancy outcomes. Since placental defects are the main cause of first-trimester miscarriages, the purpose of this review is to provide a survey of state-of-the-art human in vitro trophoblast models that can be used for the functional assessment of specific abnormalities/variants implicated in pregnancy loss. Since 2018, when primary human trophoblast stem cells were first derived, there has been rapid growth in models of trophoblast lineage. It has been found that a proper balance between self-renewal and differentiation in trophoblast progenitors is crucial for the maintenance of pregnancy. Different responses to aneuploidy have been shown in human embryonic and extra-embryonic lineages. Stem cell-based models provide a powerful tool to explore the effect of a specific aneuploidy/variant on the fetus through placental development, which is important, from a clinical point of view, for deciding on the suitability of embryos for transfer after preimplantation genetic testing for aneuploidy.  a2073-4409