Dokras A, Gardner L M G, Kirschmann D A, Seftor E A, Hendrix M J C
Department of Obstetrics and Gynecology and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
Placenta. 2002 Apr;23(4):274-80. doi: 10.1053/plac.2001.0784.
Identification of factors that play a role in regulating the highly invasive ability of human placental cells throughout gestation will contribute to a better understanding of this unique developmental process. The aims of this study were to determine whether the tumour suppressor gene maspin is present in the human placenta and plays a putative role in the regulation of cytotrophoblast invasion during placental development. The data showed that the expression of maspin mRNA was maximum in term placentae compared to the first and second trimester tissues, and absent in the HTR-SVneo (immortalized extravillous cytotrophoblast), JEG-3 and JAR (choriocarcinoma) cell lines. Maspin protein, detected by Western blot analysis, was twofold higher in the second trimester and 4.4-fold higher in the third trimester compared to the first trimester. Maspin immunohistochemical staining was localized in cytotrophoblasts with increased and more diffuse staining in the second and third trimesters. Corresponding to the period of maximum maspin expression, cytotrophoblasts isolated from term placentae had significantly lower invasive ability as compared to first and second trimester cytotrophoblasts (P< 0.03). Further, addition of recombinant maspin significantly decreased cytotrophoblast invasion in vitro by 40-50 per cent in all three trimesters of gestation. This study provides the first evidence of the temporal expression of maspin during human gestation and suggests a putative role for maspin in regulating the invasive activity of cytotrophoblasts at term. The down-regulation of maspin expression may be critical at the time of implantation and early placental development, whereas upregulation of maspin may serve as a signal for the end of cytotrophoblast invasion and gestation.
确定在整个妊娠期调节人胎盘细胞高度侵袭能力中起作用的因素，将有助于更好地理解这一独特的发育过程。本研究的目的是确定肿瘤抑制基因maspin是否存在于人胎盘中，并在胎盘发育过程中对细胞滋养层细胞侵袭的调节中发挥假定作用。数据显示，与孕早期和孕中期组织相比，足月胎盘组织中maspin mRNA的表达最高，而在HTR-SVneo（永生化绒毛外细胞滋养层）、JEG-3和JAR（绒毛膜癌）细胞系中未检测到maspin mRNA的表达。通过蛋白质免疫印迹分析检测到的maspin蛋白，与孕早期相比，在孕中期升高了两倍，在孕晚期升高了4.4倍。Maspin免疫组织化学染色定位于细胞滋养层细胞，在孕中期和孕晚期染色增加且更弥散。与maspin表达最高的时期相对应，与孕早期和孕中期的细胞滋养层细胞相比，从足月胎盘分离的细胞滋养层细胞的侵袭能力显著降低（P<0.03）。此外，添加重组maspin在体外可使妊娠所有三个阶段的细胞滋养层细胞侵袭能力显著降低40%-50%。本研究首次提供了maspin在人类妊娠期的时间表达证据，并提示maspin在足月时调节细胞滋养层细胞侵袭活性中可能发挥的作用。Maspin表达的下调在着床和早期胎盘发育时可能至关重要，而maspin的上调可能作为细胞滋养层细胞侵袭和妊娠结束的信号。
