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性激素驱动牛输卵管细胞外基质的重塑。

Sex steroids drive the remodeling of oviductal extracellular matrix in cattle.

机构信息

Departamento de Reprodução Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Pirassununga, São Paulo, Brazil.

Curso de Medicina Veterinária, Universidade Federal do Pampa, Uruguaiana, Rio Grande do Sul, Brazil.

出版信息

Biol Reprod. 2018 Sep 1;99(3):590-599. doi: 10.1093/biolre/ioy083.

DOI:10.1093/biolre/ioy083
PMID:29659700
Abstract

The extracellular matrix (ECM) is a group of molecules that offer structural and biochemical support to cells and interact with them to regulate their function. Also, growth factors (GFs) stored in the ECM can be locally released during ECM remodeling. Here, we hypothesize that the balance between ECM components and remodelers is regulated according to the ovarian steroid milieu to which the oviduct is exposed during the periovulatory period. Follicular growth was manipulated to generate cows that ovulated small follicles (SF-small corpus luteum [SCL]; n = 20) or large follicles (LF-large corpus luteum [LCL]; n = 21) and possess corresponding Estradiol (E2) and Progesterone (P4) plasmatic concentrations. Ampulla and isthmus samples were collected on day 4 (day 0 = ovulation induction) and immediately frozen or fixed. The transcriptional profile (n = 3/group) was evaluated by RNA sequencing. MMP Antibody Array was used to quantify ECM remodelers' protein abundance and immunohistochemistry to quantify type I collagen. Transcriptome analysis revealed the over-representation of ECM organization and remodeling pathways in the LF-LCL group. Transcription of ECM components (collagens), remodelers (ADAMs and MMPs), and related GFs were upregulated in LF-LCL. Protein intensities for MMP3, MMP8, MMP9, MMP13, and TIMP4 were greater for the LF-LCL group. Type I collagen content in the mucosa was greater in SF-SCL group. In conclusion, that the earlier and more intense exposure to E2 and P4 during the periovulatory period in LF-LCL animals stimulates ECM remodeling. We speculate that differential ECM regulation may contribute to oviductal receptivity to the embryo.

摘要

细胞外基质(ECM)是一组为细胞提供结构和生化支持并与之相互作用以调节其功能的分子。此外,储存在 ECM 中的生长因子(GFs)在 ECM 重塑过程中可以局部释放。在这里,我们假设 ECM 成分和重塑剂之间的平衡根据卵巢类固醇环境进行调节,而这种环境是在排卵期间输卵管暴露的。通过操纵卵泡生长来产生排卵小卵泡(SF-小黄体 [SCL];n=20)或大卵泡(LF-大黄体 [LCL];n=21)的奶牛,并具有相应的雌二醇(E2)和孕酮(P4)血浆浓度。在第 4 天(排卵诱导的第 0 天)收集壶腹部和峡部样本,并立即冷冻或固定。通过 RNA 测序评估转录谱(n=3/组)。使用 MMP 抗体阵列来定量 ECM 重塑剂的蛋白质丰度,并用免疫组织化学来定量 I 型胶原蛋白。转录组分析显示,在 LF-LCL 组中,ECM 组织和重塑途径的过度表达。在 LF-LCL 中,ECM 成分(胶原蛋白)、重塑剂(ADAMs 和 MMPs)和相关 GFs 的转录上调。MMP3、MMP8、MMP9、MMP13 和 TIMP4 的蛋白强度对于 LF-LCL 组更大。SF-SCL 组的粘膜中 I 型胶原蛋白含量更大。总之,在 LF-LCL 动物的排卵期间更早和更强烈地暴露于 E2 和 P4 会刺激 ECM 重塑。我们推测,差异 ECM 调节可能有助于输卵管对胚胎的接受性。

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