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性类固醇替代后、发情周期及妊娠早期后备母猪子宫内膜成纤维细胞生长因子7(FGF - 7)及其受体FGFR2IIIb的调控

Regulation of endometrial fibroblast growth factor 7 (FGF-7) and its receptor FGFR2IIIb in gilts after sex steroid replacements, and during the estrous cycle and early gestation.

作者信息

Wollenhaupt Karin, Welter Harald, Brüssow Klaus-Peter, Einspanier Ralf

机构信息

Research Institute for the Biology of Farm Animals, Reproductive Biology, Dummerstorf, Germany.

出版信息

J Reprod Dev. 2005 Aug;51(4):509-19. doi: 10.1262/jrd.17013. Epub 2005 Jun 24.

Abstract

The aim of this study was to characterize the effect of ovarian steroids and early gestation on the expression of fibroblast growth factor 7 (FGF-7) and its receptor (FGFR2IIIb) in the porcine endometrium. In Experiment 1, gilts were ovariectomized (OVX) on day 10 of the estrous cycle and treated thereafter with vehicle (VEH), progesterone (P4), estradiol benzoate (EB), or P4+EB. Days 12 and 20 cyclic gilts (C12 and C20) were used to determine the influence of physiologically low and high plasma estradiol and progesterone concentrations on their expression. In Experiment 2, the expression of FGF-7 and FGFR2IIIB was characterized on days 1 (G 1) and 12 (G 12) of gestation. FGF-7 and FGFR2IIIb mRNA were quantified by quantitative real-time RT-PCR, and localization of FGF-7 protein in steroid-treated and early pregnant gilts was performed by immunohistochemistry. VEH-gilts expressed both FGF-7 and FGFR2IIIB mRNA. We found a significant effect of EB, but no effects of P4 or P4+EB on the mRNA expression of FGF-7. FGFR2IIIb mRNA significantly decreased after the EB and combined P4+EB treatments, compared to P4 only substituted animals. Day 12 cyclic gilts showed significantly higher FGF-7 and FGFR2IIIb mRNA expression compared with day 20 gilts. Between day 1 and 12 of gestation, FGF-7 mRNA expression differed highly while FGFR2IIIb transcripts only varied significantly. FGF-7 protein was localized in endometrial epithelia, vascular smooth muscle, and the endothelium of different types of blood vessels. Staining was weak in VEH and P4 treated gilts, whereas it was prominent following EB and P4+EB. FGF-7 antibody strongly stained the luminal epithelium on day 12 of gestation. In summary, FGF-7 and FGFR2IIIb mRNA expression is regulated differently by exogenous ovarian steroids, assuming progesterone in connection with a specific amount of 17beta-estradiol, whereas the receptor seems to be inhibited by estradiol. Both transcripts coordinately increased during the progesterone dominated phase on day 12 both in cyclic and early pregnant gilts. We conclude that estradiol and progesterone are involved in the regulation of this ligand-receptor system, which might have an important role in preparing endometrial tissue for implantation in gilts.

摘要

本研究的目的是确定卵巢类固醇和妊娠早期对猪子宫内膜中碱性成纤维细胞生长因子7(FGF-7)及其受体(FGFR2IIIb)表达的影响。在实验1中,在发情周期的第10天对后备母猪进行卵巢切除(OVX),然后分别用赋形剂(VEH)、孕酮(P4)、苯甲酸雌二醇(EB)或P4+EB进行处理。选取发情周期第12天和第20天的周期性发情后备母猪(C12和C20),以确定生理水平的低、高血浆雌二醇和孕酮浓度对其表达的影响。在实验2中,对妊娠第1天(G1)和第12天(G12)的FGF-7和FGFR2IIIB表达进行了表征。通过定量实时RT-PCR对FGF-7和FGFR2IIIb mRNA进行定量,并通过免疫组织化学对类固醇处理的和妊娠早期的后备母猪中FGF-7蛋白进行定位。VEH处理的后备母猪同时表达FGF-7和FGFR2IIIB mRNA。我们发现EB对FGF-7的mRNA表达有显著影响,但P4或P4+EB对其无影响。与仅用P4替代的动物相比,EB和联合使用P4+EB处理后,FGFR2IIIb mRNA显著降低。发情周期第12天的后备母猪与第20天的后备母猪相比,FGF-7和FGFR2IIIb mRNA表达显著更高。在妊娠第1天至第12天之间,FGF-7 mRNA表达差异很大,而FGFR2IIIb转录本仅存在显著差异。FGF-7蛋白定位于子宫内膜上皮、血管平滑肌和不同类型血管的内皮细胞。VEH和P4处理的后备母猪染色较弱,而EB和P4+EB处理后染色明显。妊娠第12天,FGF-7抗体强烈染色腔上皮。总之,外源性卵巢类固醇对FGF-7和FGFR2IIIb mRNA表达的调节方式不同,假设孕酮与特定量的17β-雌二醇有关,而受体似乎受到雌二醇的抑制。在发情周期和妊娠早期的后备母猪中,在孕酮主导的第12天,两种转录本均协同增加。我们得出结论,雌二醇和孕酮参与了这个配体-受体系统的调节,这可能在为后备母猪的子宫内膜组织着床做准备方面发挥重要作用。

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