辅助生殖技术(ART)通常被认为是安全的;然而,新出现的证据强调了评估成年期潜在风险以进一步提高安全性的必要性.通过玻璃化重新衍生胚胎的ART程序与自然条件不同,造成体外和体内胚胎之间的显著差异,影响胎儿生理和出生后的生活。这项研究的目的是调查在出生后观察到的肝脏转录组和代谢组变化是否已经存在于妊娠结束时的胎儿肝脏中。这项研究比较了新鲜和玻璃化的兔胚胎,发现在妊娠24天时通过转移新鲜胚胎和玻璃化胚胎获得的胎儿之间的差异。重新衍生的胚胎减少了胎儿和肝脏的重量以及冠臀部的长度。然而,玻璃化胚胎的后代出生时往往体重较高,在妊娠的最后一周显示补偿性增长(59.2vs.49.8g)。RNA-Seq分析显示,与新鲜组相比,玻璃化胚胎的胎儿肝脏中有43个差异表达基因(DEGs)。值得注意的是,下调基因包括BRAT1、CYP4A7、CYP2B4、RPL23、RPL22L1、PPILAL1、A1BG、IFGGC1,LRRC57,DIPP2,UGT2B14,IRGM1,NUTF2,MPST,和PPP1R1B,而上调的基因包括ACOT8,ERICH3,UBXN2A,METTL9,ALDH3A2,类似DERPC,NR5A2样,AP-1,COG8,INHBE,PLA2G4C总的来说,这些DEGs的功能注释表明参与脂质代谢以及应激和炎症过程或免疫反应。因此,我们的结果提示玻璃化和胚胎移植操作诱导了适应性反应,在妊娠最后一周的肝脏中可以观察到这种反应.
Assisted reproduction technologies (ARTs) are generally considered safe; however, emerging evidence highlights the need to evaluate potential risks in adulthood to improve safety further. ART procedures like rederivation of embryos by
vitrification differ from natural conditions, causing significant disparities between in vitro and in vivo embryos, affecting foetal physiology and postnatal life. This study aims to investigate whether hepatic transcriptome and metabolome changes observed postnatally are already present in foetal livers at the end of gestation. This study compared fresh and vitrified rabbit embryos, finding differences between foetuses obtained by the transfer of fresh and vitrified embryos at 24 days of gestation. Rederived embryos had reduced foetal and liver weights and crown-rump length. However, the offspring of vitrified embryos tended to be born with higher weight, showing compensatory growth in the final week of gestation (59.2 vs. 49.8 g). RNA-Seq analysis revealed 43 differentially expressed genes (DEGs) in the foetal liver of vitrified embryos compared to the fresh group. Notably, downregulated genes included BRAT1, CYP4A7, CYP2B4, RPL23, RPL22L1, PPILAL1, A1BG, IFGGC1, LRRC57, DIPP2, UGT2B14, IRGM1, NUTF2, MPST, and PPP1R1B, while upregulated genes included ACOT8, ERICH3, UBXN2A, METTL9, ALDH3A2, DERPC-like, NR5A2-like, AP-1, COG8, INHBE, and PLA2G4C. Overall, a functional annotation of these DEGs indicated an involvement in lipid metabolism and the stress and inflammatory process or immune response. Thus, our results suggest that
vitrification and embryo transfer manipulation induce an adaptive response that can be observed in the liver during the last week of gestation.