Effect of Nonionizing Radiation on Progesterone Treatment in Endometrial Hyperplasia: An Experimental Rat Study

<b><i>Objectives:</i></b> The aim of the study was to evaluate the negative effect of nonionizing radiation on the treatment of endometrial hyperplasia (EH) with oral progesterone. <b><i>Design:</i></b> Forty oophorectomized Wistar Albino female rats were included in this experimental rat study. <b><i>Materials and Methods:</i></b> The 4 groups were planned as follows: Group A; sham group; Group B; group receiving oral estradiol hemihydrate 4 mg/kg/day; Group C; 4 mg/kg/day oral estradiol hemihydrate followed with 1 mg/day medroxy progesterone acetate (MPA) and Group D; 4 mg/kg/day oral estradiol hemihydrate followed with 1 mg/day MPA with exposure to nonionizing radiation at 1800 mHz/3 h/day. After the experimental model, uterine horns were sampled and the preparations were evaluated for pathological parameters (glandular density, epithelial cell length, and luminal epithelial cell length) via light microscopy. Nonionizing radiation was created by a signal generator and a compatible mobile phone. <b><i>Results:</i></b> Estrogen was found to increase all parameters related to EH (<i>p</i> &#x3c; 0.05). Progesterone treatment was found to decrease parameters related to EH (Group B vs. C; luminal epithelial cell length, glandular density, and epithelial length; 11.2 vs. 13.2 μm <i>p</i> = 0.007; 32.5 vs. 35.5, <i>p</i> = 0.068; and 219.9 μm vs. 285 µm, <i>p</i> &#x3c; 0.001, respectively). Final analyses revealed reduced effectiveness of progesterone treatment in the rats exposed to nonionizing radiation (Group C vs. D); luminal epithelial cell length, glandular density, and epithelial length (11.2 μm vs. 13.5 μm, <i>p</i> = 0.179; 32.5 vs. 52, <i>p</i> &#x3c; 0.001; and 219.9 μm vs. 374.1 μm, <i>p</i> = 0.001, respectively). <b><i>Limitations:</i></b> The limitations of our study are that the results of animal experiments may not be appropriate for direct adaptation to humans and the relatively low number of rats included in the study. <b><i>Conclusion:</i></b> Nonionizing radiation reduces the effect of progesterone in patients receiving treatment for EH.

Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer

Fluidity in cell fate or heterogeneity in cell identity is an interesting cell biological phenomenon, which at the same time poses a significant obstacle for cancer therapy. The mammary gland seems a relatively straightforward organ with stromal cells and basal- and luminal- epithelial cell types. In reality, the epithelial cell fates are much more complex and heterogeneous, which is the topic of this review. Part of the complexity comes from the dynamic nature of this organ: the primitive epithelial tree undergoes extensively remodeling and expansion during puberty, pregnancy, and lactation and, unlike most other organs, the bulk of mammary gland development occurs late, during puberty. An active cell biological debate has focused on lineage commitment to basal- and luminal- epithelial cell fates by epithelial progenitor and stem cells; processes that are also relevant to cancer biology. In this review, we discuss the current understanding of heterogeneity in mammary gland and recent insights obtained through lineage tracing, signaling assays, and organoid cultures. Lastly, we relate these insights to cancer and ongoing efforts to resolve heterogeneity in breast cancer with single-cell RNAseq approaches.

Establishment and Characterization of a Lactating Caprine Mammary Gland Luminal Epithelial Cell Line

Mammary gland is a defining characteristic of mammalian species which produces nutritious milk and plays a major role in the development of newborns. The gland contains a series of ducts and crevices leading back to alveoli, which contain milk producing cells called luminal epithelial cells. These cells, if cultured in-vitro, can be utilized to explore the metabolic processes occurring during milk production. The knowledge thus gained can be used to manipulate the system to enhance milk production and/or modify its composition. The main objective of this study was to establish a luminal epithelial cell-line from a lactating goat. Explant culture technique was used to produce primary cells from the mammary tissue of a 4-year-old lactating Saanen goat. The outgrowing cells were purified by selective trypsinization to remove fibroblast cells in 3-4 serial passages. The purified cell cultures exhibited cobblestone morphology, typical of the mammary epithelial cells, formed clear islands when plated in low density, and exhibited dome-shaped structures, if cultured for extended time. The cells stained positive with anti-human cytokeratin 18 antibodies, confirming their epithelial nature. Cell cultures also stained positive with rabbit anti-bovine &beta;-lactoglobulin antibodies, indicating milk production in these cells. The cell-line has potential as an in-vitro cell model to understand signaling during milk synthesis, mammary gland development, and testing DNA constructs for therapeutic protein secretion in milk, prior to production of transgenic goats.