Abstract：
Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.
摘要：
了解犬乳腺（CMG）的正常生理至关重要，因为它为了解犬乳腺肿瘤提供了基础参考。Ki-67表达表示的增殖指数(PI)之间的关系,随着细胞凋亡指数（AI）通过Caspase-3的表达在发情周期，在现有文献中没有充分的记载。这项研究旨在提供对整个发情周期阶段CMG中PI和AI之间相互作用的见解。对一系列不同的母犬（n=18）进行了广泛的调查。通过阴道细胞学检查确定发情周期阶段，生殖道和血清孕酮和雌二醇浓度的组织学检查。对整个乳腺链进行了组织学检查，通过使用抗Ki-67和Caspase-3抗体的双重免疫组织化学评估增殖和凋亡。PI和AI通过系统随机抽样的方法进行了评估，每个细胞类型至少计数200个细胞。在所有乳腺成分的早期发情期间，PI均显着较高，与基质细胞相比，上皮细胞中观察到的阳性细胞比例更高。在终芽内的上皮细胞中检测到最高的PI。在颅内乳腺的Ki-67标记中发现了显着差异。在上皮细胞中，孕酮浓度与PI之间呈正相关。在整个发情周期中，AI始终处于低位，在组织学成分中几乎没有差异。Caspase-3标记在尾部乳腺对中显示出最高的阳性。在小叶间充质细胞中，孕酮浓度与AI之间呈负相关和中度相关。这项研究强调了内分泌调节对乳腺组织细胞增殖指数的影响，强调在涉及犬乳腺的毒理学研究中需要考虑这些激素变化。
