Rawtani Harshal, Jackson Julia, Gao Fumei, Mellouk Namya, Myer Isabella, Mora Karina Cuevas, Fenton Suzanne E, Feng Liping
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Duke University, Durham, NC, USA.
Reprod Toxicol. 2024 Dec;130:108740. doi: 10.1016/j.reprotox.2024.108740. Epub 2024 Oct 29.
The mammary gland undergoes dynamic structural and compositional changes throughout life, influenced significantly by hormonal fluctuations and environmental factors. From embryonic development through menopause, this tissue adapts to accommodate phases such as postnatal expansion, pregnancy-induced lactation, and post-weaning involution. Hormones, growth factors, cytokines, and exogenous factors regulate these innate processes, affecting mammary epithelial cell proliferation and sensitivity, particularly in terminal end buds (TEB) and lobules, which are highly susceptible to endocrine disruption. Rodent models have provided invaluable insights into mammary gland biology, yet differences exist compared to human development, prompting the exploration of alternative models like rabbits. Additionally, there is momentum to move away from the use of nonhuman primates in safety assessments, increasing the need for evaluation tools for all tissues in the rabbit model. Rabbit mammary glands exhibit similarities to humans, making them promising for studying breast biology and pathology. However, protocols for whole-mount analysis of rabbit mammary glands are lacking due to the technical challenges of working with thicker tissue than rodent mammary glands. Here, we developed a methodology modified from rodent studies for preparing and analyzing rabbit mammary gland whole mounts, which is essential for advancing research in mammary gland biology and understanding the effects of hormonal and toxicant-induced disruption of mammary gland growth and function.
乳腺在整个生命过程中会经历动态的结构和成分变化，受到激素波动和环境因素的显著影响。从胚胎发育到更年期，该组织会进行适应性调整，以适应产后扩张、妊娠诱导泌乳和断奶后退化等阶段。激素、生长因子、细胞因子和外源性因素调节这些固有过程，影响乳腺上皮细胞的增殖和敏感性，特别是在终末芽（TEB）和小叶中，这些部位极易受到内分泌干扰的影响。啮齿动物模型为乳腺生物学提供了宝贵的见解，但与人类发育相比仍存在差异，这促使人们探索像兔子这样的替代模型。此外，在安全性评估中减少使用非人类灵长类动物的趋势日益明显，这增加了在兔子模型中对所有组织进行评估工具的需求。兔子的乳腺与人类相似，使其有望用于研究乳腺生物学和病理学。然而，由于处理比啮齿动物乳腺更厚的组织存在技术挑战，目前缺乏对兔子乳腺进行整体分析的方案。在此，我们开发了一种从啮齿动物研究中改进而来的方法，用于制备和分析兔子乳腺整体标本，这对于推进乳腺生物学研究以及理解激素和毒物诱导的乳腺生长和功能破坏的影响至关重要。
