Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models

Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models
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DOI:
10.1093/humrep/deq035
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发表时间:
2010-05-01
期刊:
影响因子:
6.1
通讯作者:
Huppertz, B.
Huppertz, B.
中科院分区:
医学1区
文献类型:
--
作者:
Moser, G.;Gauster, M.;Huppertz, B.

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滋养层细胞侵袭的途径似乎是明确的,但具体的侵袭途径还需要进一步阐明。绒毛外滋养层细胞(EVT)转化螺旋动脉,以确保胎盘在中期有适当的血液流动。妊娠早期的胚胎营养被认为是组织营养性的,而缺乏EVT也侵袭子宫腺的证据。我们建立了新的三维对峙共培养模型来阐明EVT对子宫腺的侵袭,首先将三个月的顶叶蜕膜和胎盘绒毛外植体直接对接并共培养72 h,或在预培养72 h后间接对接,以使蜕膜碎片重新上皮化。冰冻切片用免疫组织化学或免疫荧光/免疫组织化学双标染色,并与早孕胎盘现场对照。EVT直接对峙试验深入蜕膜组织,位于蜕膜上皮细胞与上皮基底膜之间。在与腺体直接接触的蜕膜基质中也可检测到EVT,有时甚至取代了腺上皮细胞。在早孕蜕膜/胎盘床的切片上也进行了类似的观察。在基底蜕膜浸润区,55%的腺体横切面(平均+/-扫描电子显微镜;n=10,6~11周)与EVT相关或被EVT侵袭。EVTS似乎突破了子宫腺的基底膜,向绒毛间隙开放其管腔。这些数据支持胎盘内母体血流开始前胚胎组织营养的假说。
Routes of trophoblast invasion seem to be clear, whereas specific invasive pathways need further elucidation. Extravillous trophoblasts (EVTs) transform spiral arteries to guarantee appropriate blood flow to the placenta in the second trimester. Embryo nutrition during the first trimester is thought to be histiotrophic, whereas proof that EVTs also invade uterine glands is lacking. We developed novel three-dimensional confrontation co-culture models to elucidate invasion of EVTs into uterine glands.First trimester decidua parietalis and placental villous explants were directly confronted and co-cultured for 72 h, or confronted indirectly after 72 h pre-culture for re-epithelialization of decidua pieces. Cryosections were stained by immunohistochemistry or immunofluorescent/immunohistochemical double labelling and compared with first trimester placentation sites in situ.EVTs deeply invaded decidual tissues in direct confrontation assays and were found between the decidual epithelial cells and epithelial basement membrane. EVTs were also detected in the decidual stroma in direct proximity to glands, sometimes even replacing glandular epithelial cells. Similar observations were made in sections from the first trimester decidua/placental bed. In the invaded parts of sections of decidua basalis, 55% +/- 7% (mean +/- SEM; n = 10, range 6-11 weeks) of glandular cross sections were associated with or infiltrated by EVTs.Using novel confrontation co-culture assays, a potential new route of EVT invasion was detected. EVTs appear to break through the basement membrane of uterine glands to open their lumen towards the intervillous space. These data support the hypothesis of histiotrophic nutrition of the embryo prior to onset of maternal blood flow within the placenta.