Department of Medical Microbiology and Immunology, Medical School, Pecs University, 12 Szigeti Street, H-7624 Pecs, Hungary.
J Reprod Immunol. 2011 Jun;90(1):50-7. doi: 10.1016/j.jri.2011.03.005. Epub 2011 May 31.
Controlled trophoblast invasion is a key process during human placentation and a prerequisite for successful pregnancy. Progesterone is one of the factors to regulate trophoblast invasiveness. Progesterone-induced blocking factor (PIBF) is a progesterone-induced molecule expressed by the trophoblast, and also by tumors. The distribution of PIBF within the first-trimester decidua coincides with sites of trophoblast invasion. Another molecule that has been implicated in the control of trophoblast invasiveness is placental leptin. Leptin inhibits the secretion of progesterone by cytotrophoblast. The aim of this work was to investigate the possible interaction of PIBF and leptins in regulating trophoblast invasion. Paraffin-embedded sections from normal first-trimester placentae, partial moles, complete moles, and choriocarcinomas were reacted with PIBF, leptin, and leptin receptor specific antibodies. PIBF-deficient trophoblast cells were generated using siRNA and leptin receptor was detected on Western blot analysis. The lysates of PIBF-treated cells were used for detecting leptin expression in a protein array. PIBF was expressed in both normal first-trimester villous trophoblast and in partial mole. Compared with this, PIBF expression was markedly decreased in complete mole and absent in choriocarcinoma. Neither leptinR nor leptin were detected in partial mole, whereas both of these molecules were present in complete mole and choriocarcinoma. Leptin receptor expression was upregulated in PIBF-deficient cells, while leptin expression was decreased in PIBF-treated cells. These data suggest that PIBF affects the expression of leptin and its receptor, and that PIBF expression is inversely related to trophoblast invasiveness.
滋养细胞侵袭的控制是人类胎盘形成的关键过程，也是成功妊娠的前提。孕激素是调节滋养细胞侵袭性的因素之一。孕激素诱导阻断因子（PIBF）是一种由滋养细胞表达的孕激素诱导分子，也由肿瘤表达。PIBF 在早孕蜕膜中的分布与滋养细胞侵袭的部位一致。另一种与滋养细胞侵袭性控制有关的分子是胎盘瘦素。瘦素抑制合体滋养细胞分泌孕激素。本研究旨在探讨 PIBF 和瘦素在调节滋养细胞侵袭性中的可能相互作用。用 PIBF、瘦素和瘦素受体特异性抗体对正常早孕胎盘、部分葡萄胎、完全葡萄胎和绒毛膜癌的石蜡包埋切片进行反应。使用 siRNA 生成 PIBF 缺陷型滋养细胞，并通过 Western blot 分析检测瘦素受体。用 PIBF 处理细胞的裂解物用于检测蛋白质阵列中的瘦素表达。PIBF 在正常早孕绒毛滋养细胞和部分葡萄胎中均有表达。相比之下，PIBF 在完全葡萄胎中的表达明显降低，在绒毛膜癌中则缺失。部分葡萄胎中未检测到瘦素受体或瘦素，而完全葡萄胎和绒毛膜癌中均存在这两种分子。在 PIBF 缺陷型细胞中，瘦素受体表达上调，而在 PIBF 处理的细胞中，瘦素表达下调。这些数据表明 PIBF 影响瘦素及其受体的表达，并且 PIBF 表达与滋养细胞侵袭性呈负相关。
