目的:这项研究旨在发现在早期切割人类胚胎中活跃的激素途径。
方法:编辑了152种激素和受体的列表,以查询8细胞人类胚胎中mRNA的微阵列数据库,两系人胚胎干细胞加上人成纤维细胞在诱导多能性之前和之后。
结果:超过一半的152种激素和受体在所有细胞类型的阵列上都是沉默的,与多能细胞或成纤维细胞阵列相比,在8细胞阵列上检测到更多的高水平或中等水平。8个激素家族基因在8个细胞阵列上被独特地检测到比干细胞阵列高至少22倍:AVPI1,CCK,CORT,FSTL4,GIP,GPHA2,OXT,和PPY表明这些蛋白质在早期发育中的新作用。通过先导免疫测定在从第3天胚胎收集的培养基中检测催产素。CRHR1和EPOR的稳健检测表明8细胞胚胎可能对母体CRH和EPO有反应。POMC和GHITM的过表达表明POMP肽产物可能在早期发育中具有未发现的作用,GHITM可能有助于线粒体重塑。在8细胞阵列上至少检测到十倍是类固醇生物合成中的两个关键酶,DHCR24和FDPS。
结论:人类8细胞胚胎可能分泌催产素,这可以刺激其自身在输卵管下的进展,并在早期神经前体发育中发挥作用。8细胞胚胎不合成生殖类固醇激素。正如以前报道的生长因子家族,早期胚胎过度表达的激素比激素受体多。
OBJECTIVE: This study is to discover hormone pathways active in early cleaving human embryos.
METHODS: A list of 152 hormones and receptors were compiled to query the microarray database of mRNAs in 8-cell human embryos, two lines of human embryonic stem cells plus human fibroblasts before and after induced pluripotency.
RESULTS: Over half of the 152 hormones and receptors were silent on the arrays of all cell types, and more were detected at high or moderate levels on the 8-cell arrays than on the pluripotent cell or fibroblast arrays. Eight hormone family genes were uniquely detected at least 22-fold higher on the 8-cell arrays than the stem cell arrays: AVPI1, CCK, CORT, FSTL4, GIP, GPHA2, OXT, and PPY suggesting novel roles for these proteins in early development. Oxytocin was detected by pilot immunoassay in culture media collected from Day 3 embryos. Robust detection of CRHR1 and EPOR suggests the 8-cell embryo may be responsive to maternal CRH and EPO. The over-expression of POMC and GHITM suggests POMP peptide products may have undiscovered roles in early development and GHITM may contribute to mitochondrial remodeling. Under-detected on the 8-cell arrays at least tenfold were two key enzymes in steroid biosynthesis, DHCR24 and FDPS.
CONCLUSIONS: The 8-cell human embryo may be secreting oxytocin, which could stimulate its own progress down the fallopian tube as well as play a role in early neural precursor development. The 8-cell embryo does not synthesize reproductive steroid hormones. As previously reported for growth factor families, the early embryo over-expresses more hormones than hormone receptors.