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牛滋养层细胞分化过程中17α-羟化酶-C17,20-裂解酶与芳香化酶细胞色素P450的相互表达:双细胞系统驱动胎盘雌激素合成。

Reciprocal expression of 17alpha-hydroxylase-C17,20-lyase and aromatase cytochrome P450 during bovine trophoblast differentiation: a two-cell system drives placental oestrogen synthesis.

作者信息

Schuler G, Ozalp G R, Hoffmann B, Harada N, Browne P, Conley A J

机构信息

Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus-Liebig-University, Frankfurter Strasse 106, D-35392 Giessen, Germany.

出版信息

Reproduction. 2006 Apr;131(4):669-79. doi: 10.1530/rep.1.01033.

Abstract

No definitive information is yet available on the steroidogenic capacity of the two morphologically distinct cell types forming the bovine trophoblast, the uninucleated trophoblast cells (UTCs) and the trophoblast giant cells (TGCs). Hence, in order to localise 17alpha-hydroxylase-C17,20-lyase (P450c17) on a cellular level and to monitor its expression as a function of gestational age, placentomes from pregnant (days 80-284; n = 19), prepartal (days 273-282; 24-36 h prior to the onset of labour; n = 3) and parturient cows (n = 5) were immunostained for P450c17 using an antiserum against the recombinant bovine enzyme. At all stages investigated, P450c17 was exclusively found in the UTCs of chorionic villi (CV), where staining was ubiquitous between days 80 and 160, but was largely restricted to primary CV and the branching sites of secondary CV between days 160 and 240. Thereafter, a distinct ubiquitous staining reoccurred in the UTCs of all CV in late pregnant, prepartal and parturient animals. Using an antiserum against human aromatase cytochrome P450 (P450arom), specific cytoplasmic staining was observed in TGCs. In placentomes from pregnant cows, staining intensity was higher in mature compared with immature TGCs and was more pronounced in the trophoblast covering big stem villi compared with the trophoblast at other sites of the villous tree. In placentomes of a parturient cow, specific staining was only found in mature TGCs that survived the normal, but substantial, prepartal decline in TGC numbers. These results clearly showed that bovine UTCs and TGCs exhibit different steroidogenic capacities, constituting a 'two-cell' organisation for oestrogen synthesis. P450c17 expression appears to be quickly down-regulated and P450arom is up-regulated when UTCs enter the TGC differentiation pathway.

摘要

关于构成牛滋养层的两种形态上不同的细胞类型,即单核滋养层细胞(UTCs)和滋养层巨细胞(TGCs)的类固醇生成能力,目前尚无确切信息。因此,为了在细胞水平上定位17α-羟化酶-C17,20-裂解酶(P450c17)并监测其作为胎龄函数的表达情况,对怀孕(第80 - 284天;n = 19)、产前(第273 - 282天;分娩开始前24 - 36小时;n = 3)和产后母牛(n = 5)的胎盘叶进行免疫染色,使用针对重组牛酶的抗血清检测P450c17。在所有研究阶段,P450c17仅在绒毛膜绒毛(CV)的UTCs中发现,在第80天至160天之间染色普遍存在,但在第160天至240天之间主要局限于初级CV和次级CV的分支部位。此后,在怀孕后期、产前和产后动物的所有CV的UTCs中再次出现明显的普遍染色。使用针对人芳香化酶细胞色素P450(P450arom)的抗血清,在TGCs中观察到特异性细胞质染色。在怀孕母牛的胎盘叶中,成熟TGCs的染色强度高于未成熟TGCs,并且与绒毛树其他部位的滋养层相比,覆盖大主干绒毛的滋养层染色更明显。在一头产后母牛的胎盘叶中,特异性染色仅在成熟TGCs中发现,这些TGCs在产前TGC数量正常但大量减少后存活下来。这些结果清楚地表明,牛UTCs和TGCs表现出不同的类固醇生成能力,构成了雌激素合成的“双细胞”组织。当UTCs进入TGC分化途径时,P450c17表达似乎迅速下调,而P450arom上调。

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