State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
PLoS One. 2012;7(7):e40528. doi: 10.1371/journal.pone.0040528. Epub 2012 Jul 13.
Parathyroid hormone-like hormone (PTHLH) was first identified as a parathyroid hormone (PTH)-like factor responsible for humoral hypercalcemia in malignancies in the 1980s. Previous studies demonstrated that PTHLH is expressed in multiple tissues and is an important regulator of cellular and organ growth, development, migration, differentiation, and survival. However, there is a lack of data on the expression and function of PTHLH during preimplantation embryonic development. In this study, we investigated the expression characteristics and functions of PTHLH during mouse preimplantation embryonic development. The results show that Pthlh is expressed in mouse oocytes and preimplantation embryos at all developmental stages, with the highest expression at the MII stage of the oocytes and the lowest expression at the blastocyst stage of the preimplantation embryos. The siRNA-mediated depletion of Pthlh at the MII stage oocytes or the 1-cell stage embryos significantly decreased the blastocyst formation rate, while this effect could be corrected by culturing the Pthlh depleted embryos in the medium containing PTHLH protein. Moreover, expression of the pluripotency-related genes Nanog and Pou5f1 was significantly reduced in Pthlh-depleted embryos at the morula stage. Additionally, histone acetylation patterns were altered by Pthlh depletion. These results suggest that PTHLH plays important roles during mouse preimplantation embryonic development.
甲状旁腺激素样激素（PTHLH）于 20 世纪 80 年代首次被鉴定为一种与甲状旁腺激素（PTH）相似的因子，可导致恶性肿瘤中的体液性高钙血症。先前的研究表明，PTHLH 在多种组织中表达，是细胞和器官生长、发育、迁移、分化和存活的重要调节剂。然而，关于 PTHLH 在胚胎植入前发育过程中的表达和功能的数据还很缺乏。在这项研究中，我们研究了 PTHLH 在小鼠胚胎植入前发育过程中的表达特征和功能。结果表明，Pthlh 在卵母细胞和所有发育阶段的胚胎前植入期均有表达，在卵母细胞的 MII 期表达最高，在胚胎前植入期的囊胚期表达最低。在 MII 期卵母细胞或 1 细胞期胚胎中，用 siRNA 介导的 Pthlh 耗竭可显著降低囊胚形成率，而在含有 PTHLH 蛋白的培养基中培养 Pthlh 耗竭的胚胎可纠正这种效应。此外，在桑椹胚阶段，Pthlh 耗竭的胚胎中多能性相关基因 Nanog 和 Pou5f1 的表达明显降低。此外，Pthlh 耗竭改变了组蛋白乙酰化模式。这些结果表明，PTHLH 在小鼠胚胎植入前发育过程中发挥重要作用。
