The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide 5005, Australia.
Development. 2010 Dec;137(24):4229-38. doi: 10.1242/dev.059261. Epub 2010 Nov 10.
Each ovarian cycle, the mammary gland epithelium rotates through a sequence of hormonally regulated cell proliferation, differentiation and apoptosis. These studies investigate the role of macrophages in this cellular turnover. Macrophage populations and their spatial distribution were found to fluctuate across the cycle. The number of macrophages was highest at diestrus, and the greatest number of macrophages in direct contact with epithelial cells occurred at proestrus. The physiological necessity of macrophages in mammary gland morphogenesis during the estrous cycle was demonstrated in Cd11b-Dtr transgenic mice. Ovariectomised mice were treated with estradiol and progesterone to stimulate alveolar development, and with the progesterone receptor antagonist mifepristone to induce regression of the newly formed alveolar buds. Macrophage depletion during alveolar development resulted in a reduction in both ductal epithelial cell proliferation and the number of alveolar buds. Macrophage depletion during alveolar regression resulted in an increased number of branch points and an accumulation of TUNEL-positive cells. These studies show that macrophages have two roles in the cellular turnover of epithelial cells in the cycling mammary gland; following ovulation, they promote the development of alveolar buds in preparation for possible pregnancy, and they remodel the tissue back to its basic architecture in preparation for a new estrous cycle.
每个卵巢周期，乳腺上皮细胞都会经历一系列受激素调节的细胞增殖、分化和凋亡。这些研究探讨了巨噬细胞在细胞更替中的作用。研究发现，巨噬细胞群体及其空间分布在整个周期中都有波动。在发情间期，巨噬细胞数量最高，与上皮细胞直接接触的巨噬细胞数量在发情前期最多。在发情周期中，乳腺形态发生过程中巨噬细胞的生理必要性在 Cd11b-Dtr 转基因小鼠中得到了证明。去卵巢小鼠用雌二醇和孕激素处理以刺激肺泡发育，并使用孕激素受体拮抗剂米非司酮诱导新形成的肺泡芽退化。在肺泡发育过程中耗尽巨噬细胞会导致导管上皮细胞增殖减少和肺泡芽数量减少。在肺泡退化过程中耗尽巨噬细胞会导致分支点数量增加和 TUNEL 阳性细胞积累。这些研究表明，巨噬细胞在周期性乳腺上皮细胞的细胞更替中具有两个作用；排卵后，它们促进肺泡芽的发育，为可能的怀孕做准备，然后重塑组织回到其基本结构，为新的发情周期做准备。
