Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Department of Pathobiology, Ontario Veterinary College, Guelph, ON, Canada.
Theriogenology. 2024 Oct 1;227:151-156. doi: 10.1016/j.theriogenology.2024.07.014. Epub 2024 Jul 19.
Prostaglandins have many roles in the equine reproductive tract, including but not limited to luteolysis, luteal support, ovulation, transport through the uterine tube, uterine contraction, embryonic mobility, inflammation, and fibrosis. Altered secretion of inflammatory proteins are likely to disrupt the balance of endometrial function and could impair fertility. Our overall goal was to measure the expression of several prostaglandin- and inflammation-related genes in mares with different degrees of endometrial histological changes. Our hypothesis was that mares with neutrophilic and lymphocytic plasmocytic inflammation, fibrosis, or different biopsy grades would have altered concentrations of prostaglandin E2 (PGE2) and F2α (PGF2α), as well as altered expression of inflammation- and prostaglandin-related genes, compared to mares with minimal to no histological changes on biopsy evaluation. Forty-five endometrial biopsies from estrous mares were assessed by a reproductive pathologist for the degree of neutrophilic inflammation, lymphocytic and plasmocytic inflammation, and fibrosis, and a biopsy grade was assigned based on the Kenney-Doig system. A low-volume uterine lavage was collected from a subset of twenty-six mares prior to biopsy collection and was used to measure PGE2 and PGF2α concentrations via ELISA. Total RNA was extracted from biopsies and mRNA expression was evaluated for twenty-five genes of interest. A restricted maximum likelihood linear model was used to compare differences of mRNA expression, with a statistical significance set at P < 0.05. There was no difference in the abundance of PGE2 or PGF2α between any of the variables tested. Mares with endometrial biopsy grade I had lower expression of NF-kB, PTGS1 and HPGD compared to grade IIA or IIB (P < 0.05). Mares with neutrophilic inflammation had decreased expression of NF-kB, PTGS1, PTGER4, CBR1, mPGES2 and PTGIS compared to mares without inflammation. Mares with mild or minimal endometrial fibrosis had increased expression of mPGES2 and PTGIS, compared to mares with moderate endometrial fibrosis. In conclusion, several genes were identified to be differentially expressed in mares with histological changes compared to mares with no to minimal histological changes. The presence of inflammation and fibrosis may alter the concentration of prostaglandins in endometrial tissue, which could impair many of the uterine reproductive and immune functions during estrus, affecting early embryo survival.
前列腺素在马的生殖道中具有多种作用，包括但不限于黄体溶解、黄体支持、排卵、通过子宫管运输、子宫收缩、胚胎活动、炎症和纤维化。炎症蛋白分泌的改变可能破坏子宫内膜功能的平衡，并可能损害生育能力。我们的总体目标是测量具有不同程度子宫内膜组织学变化的母马中几种与前列腺素和炎症相关的基因的表达。我们的假设是，与活检评估中最小至无组织学变化的母马相比，具有中性粒细胞和淋巴细胞浆细胞炎症、纤维化或不同活检分级的母马，其前列腺素 E2 (PGE2) 和 F2α (PGF2α) 浓度以及与炎症和前列腺素相关的基因表达会发生改变。45 份发情母马的子宫内膜活检由生殖病理学家评估中性粒细胞炎症、淋巴细胞和浆细胞炎症以及纤维化的程度，并根据 Kenney-Doig 系统分配活检分级。在采集活检前，从小部分 26 头母马中采集低容量子宫冲洗液，通过 ELISA 测量 PGE2 和 PGF2α 浓度。从活检中提取总 RNA，并评估 25 个感兴趣的基因的 mRNA 表达。使用受限最大似然线性模型比较 mRNA 表达的差异，统计显著性设为 P < 0.05。在测试的任何变量之间，PGE2 或 PGF2α 的丰度均无差异。与 IIA 或 IIB 级相比，I 级子宫内膜活检的母马 NF-kB、PTGS1 和 HPGD 的表达较低（P < 0.05）。与无炎症的母马相比，具有中性粒细胞炎症的母马 NF-kB、PTGS1、PTGER4、CBR1、mPGES2 和 PTGIS 的表达降低。与中度子宫内膜纤维化的母马相比，轻度或最小子宫内膜纤维化的母马 mPGES2 和 PTGIS 的表达增加。总之，与无组织学变化或最小组织学变化的母马相比，在具有组织学变化的母马中鉴定出几个差异表达的基因。炎症和纤维化的存在可能改变子宫内膜组织中前列腺素的浓度，这可能会损害发情期间子宫的许多生殖和免疫功能，影响早期胚胎存活。
