BACKGROUND Despite being one of the major causes of infertility in mares, the mechanisms responsible for equine endometrosis are still unclear and controversial. In the last few years, many investigations focused on local immune response modulation. Since it is generally accepted that endometrial fibrosis increases with age, we hypothesize that older mares could show altered local immune modulation, initiating a pro-inflammatory and tissue remodeling cascade of events that could lead to endometrosis. The aim of this study, indeed, is to evaluate and describe the local gene expression of genes involved in acute inflammatory response and fibrosis (COL1A1, COL3A1, TNFA, MMP9, IL6, TGFB1 and TGFBR1), together with others associated to immune modulation (DEFB4B, IDO1 and FOXP3), in uterine specimens from mares of different age. RESULTS Twenty-five Standardbred mares were involved in the study with age ranging from 7 to 19 years (mean 10.40 ± 4.42). They were divided by age into two groups: G1 (n = 15, less than 10 years old) and G2 (N = 10, greater than 11 years old). Specimens from the uterus' right horn-body junction were collected and processed for histology evaluation and RT-qPCR assay.Gene expression of DEFB4B, MMP9 and TNFA was higher in younger mares, suggesting a balance in immune modulation and tissue remodeling. Interleukin-6 and COL3A1 gene expressions were greater in older animals, probably indicating inflammatory pathways activation and fibrosis increase. Although no differences in fibrosis and inflammation distribution could be found with histological examination among G1 and G2, our results suggest a possible involvement of DEF4BB in regulating the local immune response in younger mare's uterus (G1); age may contribute to the dis-regulation of DEFB4B transcription and, indirectly, influence the extracellular matrix homeostasis. Transcription of IDO1 and FOXP3 genes, instead, does not seem to be age related, or to be involved in local immune-response and tissue remodeling functions. CONCLUSIONS Further investigations are needed in order to clarify the interactions between the expression of DEFB4B, IL6, TNFA, COL3A1 and MMP9 and other local signals of immune-modulation and tissue remodeling, in mares in a prospective study design.

中文翻译：

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在繁殖季节，不同年龄的母马的子宫内膜中防御素-B基因的表达不同。

背景技术尽管是母马不育症的主要原因之一，但马内膜异位症的发病机制仍不清楚和有争议。在过去的几年中，许多研究集中在局部免疫应答调节上。由于人们普遍认为子宫内膜纤维化会随着年龄的增长而增加，因此我们假设年长的母马可能显示出改变的局部免疫调节作用，从而引发可能导致子宫内膜异位的事件的促炎性和组织重塑。确实，这项研究的目的是评估和描述与急性炎症反应和纤维化有关的基因（COL1A1，COL3A1，TNFA，MMP9，IL6，TGFB1和TGFBR1）以及与免疫调节相关的其他基因的局部基因表达（ DEFB4B，IDO1和FOXP3），来自不同年龄的母马的子宫标本。结果本研究涉及了25只标准母马，年龄在7至19岁之间（平均10.40±4.42）。他们按年龄分为两组：G1（n = 15，小于10岁）和G2（N = 10，大于11岁）。收集子宫右角体交界处的标本并进行组织学评估和RT-qPCR分析，年轻母马中DEFB4B，MMP9和TNFA的基因表达较高，表明免疫调节和组织重塑之间存在平衡。白细胞介素6和COL3A1基因表达在较大的动物中更高，这可能表明炎症途径激活和纤维化增加。尽管通过组织学检查在G1和G2之间没有发现纤维化和炎症分布的差异，我们的结果表明，DEF4BB可能参与调节年轻母马子宫（G1）的局部免疫反应。年龄可能会导致DEFB4B转录失调，并间接影响细胞外基质稳态。相反，IDO1和FOXP3基因的转录似乎与年龄无关，或与局部免疫应答和组织重塑功能有关。结论在前瞻性研究设计中，需要进一步研究以阐明母马中DEFB4B，IL6，TNFA，COL3A1和MMP9的表达与免疫调节和组织重塑的其他局部信号之间的相互作用。相反，IDO1和FOXP3基因的转录似乎与年龄无关，或与局部免疫应答和组织重塑功能有关。结论在前瞻性研究设计中，需要进一步研究以阐明母马中DEFB4B，IL6，TNFA，COL3A1和MMP9的表达与免疫调节和组织重塑的其他局部信号之间的相互作用。相反，IDO1和FOXP3基因的转录似乎与年龄无关，或与局部免疫应答和组织重塑功能有关。结论在前瞻性研究设计中，需要进一步研究以阐明母马中DEFB4B，IL6，TNFA，COL3A1和MMP9的表达与免疫调节和组织重塑的其他局部信号之间的相互作用。