Domino Malgorzata, Jasinski Tomasz, Kautz Ewa, Juszczuk-Kubiak Edyta, Ferreira-Dias Graça, Zabielski Romuald, Sady Maria, Gajewski Zdzislaw
Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland.
Department of Morphology and Function, CIISA- Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
Theriogenology. 2020 Apr 15;147:18-24. doi: 10.1016/j.theriogenology.2020.01.055. Epub 2020 Jan 29.
Equine endometrosis is a multifactorial chronic degenerative condition, considered to be one of a major causes of equine infertility. The formation of periglandular fibrosis seems to be linked to chronic inflammation of the mare endometrium in a paracrine way and in a response to numerous forms of inflammatory stimuli elicit the net deposition of extracellular matrix (ECM) around the endometrial glands and stroma. We hypothesized some of these stimuli, such as monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and hyaluronan synthases (HASs), may share the nuclear factor-κB (NF-κB) dependent activation pathway. This study aimed to determine whether mRNA expression of MCP-1, IL-6, HASs, and proteins of canonical (RelA/NK-κβ1) and noncanonical (NK-κβ2) signaling pathways for NF-kB would change in subsequent categories of endometrosis during the estrous cycle. The expression of selected genes was established in mare endometrium (n = 80; Kenney and Doig categories I, IIA, IIB, III), obtained in the follicular phase (FLP) and mid-luteal phase (MLP). The high expression of RelA mRNA was observed in III, whereas of NK-κβ1 and NK-κβ2 also in IIA, and IIA and IIB, respectively. The expression of MCP-1 mRNA occurred constantly, regardless of the category, whereas IL-6 mRNA was low in IIA, IIB, and III. The expression of HAS 1 was high in IIA and HAS 3 in IIA, IIB, and III. All those changes were observed in FLP, but not MLP. Our results suggest that NF-κB may be involved in progression of the chronic degenerative condition of the mare endometrium, on both canonical and noncanonical pathways. The most important changes in target genes expression were observed only in FLP, which may suggest the hormone-dependent activation of the NF-κB-dependent fibrosis pathway.
马子宫内膜异位症是一种多因素慢性退行性疾病，被认为是马不孕症的主要原因之一。腺周纤维化的形成似乎以旁分泌方式与母马子宫内膜的慢性炎症相关，并且对多种形式的炎症刺激的反应引发了子宫内膜腺体和基质周围细胞外基质（ECM）的净沉积。我们推测其中一些刺激因素，如单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）和透明质酸合酶（HASs），可能共享核因子-κB（NF-κB）依赖性激活途径。本研究旨在确定在发情周期中，MCP-1、IL-6、HASs的mRNA表达以及NF-κB的经典（RelA/NK-κβ1）和非经典（NK-κβ2）信号通路的蛋白质在随后的子宫内膜异位症类别中是否会发生变化。在卵泡期（FLP）和黄体中期（MLP）获得的母马子宫内膜（n = 80；肯尼和多伊格分类I、IIA、IIB、III）中确定了所选基因的表达。在III类中观察到RelA mRNA的高表达，而在IIA类中也观察到NK-κβ1的高表达，在IIA类和IIB类中分别观察到NK-κβ2的高表达。无论类别如何，MCP-1 mRNA的表达持续存在，而IIA类和IIB类以及III类中的IL-6 mRNA较低。IIA类中HAS 1的表达较高，IIA类、IIB类和III类中HAS 3的表达较高。所有这些变化都在卵泡期观察到，而在黄体中期未观察到。我们的结果表明，NF-κB可能参与母马子宫内膜慢性退行性疾病的进展，在经典和非经典途径中均如此。仅在卵泡期观察到靶基因表达的最重要变化,这可能表明NF-κB依赖性纤维化途径的激素依赖性激活。
