REGULATION OF PLACENTAL DEVELOPMENT BY ESTROGEN

目前的研究将检验雌激素对乳腺癌的发病有重要影响的假设。 在编程增殖和/或形态 细胞滋养层细胞的分化和胎盘的生长 狒狒怀孕通过发育调节，在一个 自分泌/旁分泌方式，表达和产生IGF- IL/IGFBP-2、EGF/EGF受体。滋养层的个体发生调节 增殖/形态分化和生长因子 表达将在从狒狒获得的胎盘中测定， 妊娠第45、60和100天（足月= 184天）。的作用 将在获得的胎盘中研究雌激素对相同参数的影响 雌激素水平过早升高的狒狒 怀孕早期。雌激素对肽生长的时间效应 因子表达和滋养层细胞增殖/形态学 将在短期研究（24和48小时）中确定分化 在妊娠第45天向狒狒注射雄烯二酮后）。 滋养层细胞增殖将通过PCNA（DNA指数）来评估 复制），形态分化将通过 组织学和CS产生。mRNA的定量和定位 并测定IGF-II/IGFBP-2、EGF/EGF受体蛋白 通过RT-PCR/北方/Western印迹和原位杂交， 分别这项拟议中的研究有望提供新的见解 胎盘生长的发育调节， 在灵长类动物怀孕早期的分化。

The present study will test the hypothesis that estrogen has a major role in programming the proliferation and/or morphological differentiation of cytotrophoblasts and growth of the placenta during baboon pregnancy through developmental regulation, in an autocrine/paracrine manner, of expression and production of IGF- lI/IGFBP-2, EGF/EGF receptor. Ontogenetic regulation of trophoblast proliferation/ morphological differentiation and growth factor expression will be determined in placentas obtained from baboons on days 45, 60 and 100 of gestation (term = 184 days). The role of estrogen on the same parameters will be studied in placentas obtained from baboons in which estrogen levels have been prematurely elevated early in pregnancy. The temporal effect of estrogen on peptide growth factor expression and trophoblast proliferation/morphological differentiation will be determined in short-term studies (24 and 48 h after injection of androstenedione to baboons on day 45 of pregnancy). Trophoblast proliferation will be assessed by PCNA (index of DNA replication), and morphological differentiation will be assessed by histology and CS production. Quantification and localization of mRNAs and proteins for IGF-II/IGFBP-2, EGF/EGF receptor will be determined by RT-PCR/Northern/Western blot and in situ hybridization, respectively. The proposed study is expected to provide new insight into the developmental regulation of placental growth and differentiation during early primate pregnancy.