PRODUCTION OF GROWTH FACTORS BY EARLY MAMMALIAN EMBRYOS

激素和生长因子在早期阶段的作用 对哺乳动物的发育知之甚少。 在过去十年中， 已经很明显，处于几个发育阶段的胚胎 生长因子，其中一些表现出转化生长的特性 因素（TGF）。 TGF通过其诱导软琼脂生长的能力来测定。 非转化细胞，如正常大鼠肾（NRK）细胞的生长。 胚胎TGF样生长因子最初是在 从妊娠中期和晚期的小鼠胚胎制备的提取物。 最近，我们已经确定，从囊胚培养的胚胎 诱导NRK软琼脂生长的阶段性释放生长因子 细胞 虽然生产这些产品的精确发展阶段 因素开始还没有建立，数据表明，这些 因子由与早期植入后相关的细胞类型释放 胚胎 然而，尚未确定这些因素是否 在发展的早期阶段释放。 此外，测定 虽然相对敏感，但无法明确识别 所涉及的生长因子。 本申请提出解决几个 关于TGF样生长因子释放的重要问题 小鼠胚胎：1）它们的身份是什么？ 2)他们什么时候开始 生产？ 3)它们的释放是否受到干扰 发展？ 4)这些因子是由特定的胚胎组织产生的吗？ 这些问题将通过采用一系列生物测定来解决， 允许TGF和相关生长因子的鉴定。 工作 本申请中提出的建议将有助于澄清增长的作用 在早期发展过程中的因素，并帮助确定是否进一步研究 的胚胎生长因子可能产生适合于 监测正常的着床前发育。

The roles of hormones and growth factors during the early stages of mammalian development are poorly understood. During the past decade, it has become apparent that embryos at several stages of development produce growth factors, some of which exhibit the properties of transforming growth factors (TGFs). TGFs are assayed by their ability to induce the soft agar growth of non-transformed cells, such as normal rat kidney (NRK) cells. The TGF-like growth factors from embryos were initially observed in extracts prepared from mouse embryos at mid and late stages of gestation. Recently, we have determined that embryos cultured from the blastocyst stage release growth factors that induce the soft agar growth of NRK cells. Although the precise developmental stage when production of these factors begins has not been established, the data suggest that these factors are released by cell types associated with early postimplantation embryos. However, it has not been determined whether these factors are released at earlier stages of development. Furthermore, the assay employed, although relatively sensitive, could not unambiguously identify the growth factors involved. This application proposes to address several important questions concerning TGF-like growth factors released by early mouse embryos: 1) What are their identities? 2) When are they first produced? 3) Is their release modified by conditions that interfere with development? 4) Are these factors produced by specific embryonic tissues? These questions will be addressed by employing a battery of bioassays that permit the identification of TGFs and related growth factors. The work proposed in this application will help to clarify the roles of growth factors during early development and help determine whether further study of embryonic growth factors is likely to yield assays suitable for monitoring normal preimplantation development.