Department of Genetics and Animal Breeding, Faculty of Veterinary Medicine and Animal Science, Poznań University of Life Sciences, Poznań, Poland.
Department of Animal Reproduction with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Reprod Domest Anim. 2022 Jul;57(7):771-783. doi: 10.1111/rda.14121. Epub 2022 Apr 8.
The most common uterine diseases in bitches occurring during diestrus are cystic endometrial hyperplasia (CEH) and pyometra. These diseases can coexist as CEH-pyometra complex (CEH-P). Their pathogenesis has not been fully explained. Peroxisome proliferator-activated receptors (PPARs) are important factors regulating mammalian reproductive function and inflammatory processes. Although there is a lack of data concerning the expression of PPARs in the canine endometrium during CEH and CEH-P, we hypothesized that they might be involved in the development of pathological disorders of the canine endometrium. Therefore, the current study was conducted to evaluate and compare PPARα, PPARδ and PPARγ mRNA expression using quantitative real-time PCR (qPCR) and their immunolocalization using immunohistochemistry (IHC) staining in the endometrium of clinically healthy bitches (control group; n = 8) and those with CEH (n = 8) or CEH-P (n = 8). For quantification, the arithmetic means of all intensities of immunostaining from the cells were measured with the optical density. PPARα, PPARδ and PPARγ were detected in the luminal epithelium, glandular epithelium and stromal cells. The mRNA transcription of PPARα was higher in the CEH group than in the control group (p < .05). Additionally, the mRNA expression and immunostaining intensities of PPARδ and PPARγ in the endometrium in the CEH-P group were downregulated relative to those in the control group (p < .05). Moreover, the serum progesterone concentration measured by direct radioimmunoassay was decreased in the CEH-P group compared to the control group (p < .001) and CEH group (p < .05). The obtained results indicate that PPARs are present in the canine endometrium and that their mRNA profile and intensity levels change under pathological conditions such as CEH and CEH-P. This finding may suggest a correlation between changes in the PPAR expression profile and hormonal disturbances, as well as the potential involvement of PPARs in signal transduction during inflammatory processes occurring in the endometrium during CEH-P. These results pave the way to further research into the role of PPARs in the pathogenesis of CEH and CEH-P in female dogs.
在发情期，母犬最常见的子宫疾病是囊性子宫内膜增生（CEH）和子宫积脓。这些疾病可能同时存在，形成 CEH-子宫积脓综合征（CEH-P）。其发病机制尚未完全阐明。过氧化物酶体增殖物激活受体（PPARs）是调节哺乳动物生殖功能和炎症过程的重要因素。尽管有关犬子宫内膜 CEH 和 CEH-P 期间 PPARs 表达的数据不足，但我们假设它们可能参与犬子宫内膜病理性疾病的发展。因此，本研究旨在使用定量实时 PCR（qPCR）评估和比较 PPARα、PPARδ 和 PPARγ mRNA 的表达，并使用免疫组织化学（IHC）染色评估其在临床健康母犬（对照组；n=8）和患有 CEH（n=8）或 CEH-P（n=8）的犬子宫内膜中的免疫定位。为了定量，用光学密度测量细胞内所有免疫染色强度的算术平均值。PPARα、PPARδ 和 PPARγ 在腔上皮、腺上皮和基质细胞中均有检测到。CEH 组的 PPARα mRNA 转录高于对照组（p<0.05）。此外，CEH-P 组的 PPARδ 和 PPARγ 的子宫内膜 mRNA 表达和免疫染色强度相对对照组下调（p<0.05）。此外，直接放射免疫测定法测量的 CEH-P 组血清孕酮浓度与对照组（p<0.001）和 CEH 组（p<0.05）相比降低。研究结果表明，PPARs 存在于犬子宫内膜中，其 mRNA 谱和强度水平在 CEH 和 CEH-P 等病理条件下发生变化。这一发现可能表明 PPAR 表达谱的变化与激素紊乱之间存在相关性，以及 PPAR 在 CEH-P 期间子宫内膜炎症过程中的信号转导中可能发挥作用。这些结果为进一步研究 PPAR 在雌性犬 CEH 和 CEH-P 发病机制中的作用铺平了道路。
