Most iPSC-derived nuclear transfer fetuses result in miscarriage during postimplantation development. (A) A schematic showing the construction of iPSC-derived embryos. OKSM indicates OCT4, KLF4, SOX2, and C-MYC. (B) WT fetuses and iPSC-derived fetuses. Whereas iPSC-derived fetuses appear alive and similar to WT fetuses at GD20, most are resorbing by GD25. [Scale bars, 2 mm (Upper), 5 mm (Lower).] (C) Chorioallantoic fusion defects were observed on day 20 iPSC-derived placentas. The white arrowhead indicates allantois. The yellow arrowhead indicates chorion. The green arrowhead indicates fetus. iPSC-derived allantois exhibited impaired blood flow within the vessels. Histological abnormalities of chorion observed in day 20 iPSC-derived placentas manifest by a thin trophoblast layer. WT placentas at day 20 showing normal morphology of chorion with primary chorionic villi. [Scale bars, 10 mm (Upper), 500 μm (Middle), 200 μm (Lower).] (D) Pregnancy rates for recipients carrying pig natural fertilization embryos, pig fibroblast-derived embryos, and pig iPSC-derived embryos. Values are pregnancy rate means ± SEM and were obtained from three independent experiments. The iPSC-derived embryos show significant lower pregnancy rate compared with the fibroblast-derived embryos at GD25 (P = 0.009, two-tailed Student’s t test), GD45 (P = 0.006, two-tailed Student’s t test), GD60 (P = 0.006, two-tailed Student’s t test), and full term (0.003, two-tailed Student’s t test).