Rider V, Psychoyos A
Department of Anatomy and Cellular Biology, Tufts University School of Veterinary Medicine, Medicine and Dental Medicine, Boston, Massachusetts 02111.
J Endocrinol. 1994 Feb;140(2):239-49. doi: 10.1677/joe.0.1400239.
Recent studies suggest that hormonal control of uterine cell proliferation may be moderated by polypeptide growth factors. It remains to be determined, however, whether growth factors cause or are the consequence of hormone action. Basic fibroblast growth factor (bFGF) has been shown to influence cell proliferation and differentiation of a variety of mesoderm-derived cells. To elucidate the regulatory mechanisms controlling stromal cell proliferation and differentiation required for embryo implantation further, immunohistochemical localization of the progesterone receptor and bFGF have been studied. The cell-specific distribution of these proteins was determined in the rat uterus during early pregnancy and after injection of the progesterone receptor antagonist mifepristone (RU 486) at days 1 and 2 post coitum (p.c.) to block implantation. Cell division was restricted to luminal and glandular epithelial cells in pregnant and RU 486-treated rats at day 3 p.c. At day 4 of pregnancy, cell proliferation switched from the epithelia to the stroma in pregnant rats, but after RU 486 treatment division of stromal cells was inhibited significantly (P < 0.05). Progesterone receptor distribution was altered and bFGF was absent in RU 486-blocked stromal cells. Expression of bFGF in luminal and glandular epithelial cells, however, was insensitive to the effects of progesterone receptor antagonism. bFGF content was stimulated in the luminal epithelium and in decidual cells by the implanting embryo. These results indicate that repression of progesterone receptor function in early pregnancy results in a cell-specific loss of bFGF from stromal cells and inhibition of their proliferation. The results further suggest that the regulation of endometrial cell bFGF content is modulated at the site of implantation by the embryo.
近期研究表明，子宫细胞增殖的激素调控可能受到多肽生长因子的调节。然而，生长因子是激素作用的原因还是结果仍有待确定。碱性成纤维细胞生长因子（bFGF）已被证明可影响多种中胚层来源细胞的增殖和分化。为了进一步阐明胚胎着床所需的基质细胞增殖和分化的调控机制，我们研究了孕激素受体和bFGF的免疫组织化学定位。在妊娠早期以及在交配后第1天和第2天注射孕激素受体拮抗剂米非司酮（RU 486）以阻断着床的大鼠子宫中，确定了这些蛋白质的细胞特异性分布。在妊娠第3天，妊娠大鼠和接受RU 486治疗的大鼠的细胞分裂仅限于腔上皮和腺上皮细胞。在妊娠第4天，妊娠大鼠的细胞增殖从上皮细胞转向基质细胞，但在RU 486治疗后，基质细胞的分裂受到显著抑制（P < 0.05）。在RU 486阻断的基质细胞中，孕激素受体分布发生改变且bFGF缺失。然而，腔上皮和腺上皮细胞中bFGF的表达对孕激素受体拮抗作用不敏感。着床胚胎刺激了腔上皮和蜕膜细胞中bFGF的含量。这些结果表明，妊娠早期孕激素受体功能的抑制导致基质细胞中bFGF的细胞特异性丧失及其增殖受到抑制。结果还进一步表明，胚胎在着床部位调节子宫内膜细胞bFGF的含量。
