Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology Roberto Alcântara Gomes, State University of Rio de Janeiro, UERJ, Brazil.
Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology Roberto Alcântara Gomes, State University of Rio de Janeiro, UERJ, Brazil.
Placenta. 2018 Apr;64:7-16. doi: 10.1016/j.placenta.2018.02.001. Epub 2018 Feb 12.
Bone marrow cells (BMC) from obese adult mice display an increased apoptosis rate over proliferation. Hematopoietic stem cells (HSC) form all blood cells and are important BMC used in cell therapy. Because it is known that prenatal development can be affected by adverse metabolic epigenetic programming from the maternal organism, this work aimed to investigate the effects of maternal overweight on placenta and fetal liver hematopoietic niches.
Overweight was induced in female mice by overfeeding during lactation. After Swiss females were mated with healthy males, fetuses at 19 dpc (day post conception) and placentas were analyzed. Maternal biometric parameters were compared, and hematopoiesis in the dissociated placenta and fetal liver cells was analyzed by flow cytometry. Placenta morphology and protein content were also studied.
The model induced accumulation of adipose tissue, weight gain, and maternal hyperglycemia. Placentas from the overfed group (OG) displayed altered morphology, higher carbohydrate and lipid deposition, and increased protein content of fibronectin and PGC-1α. Cytometric analysis showed that placentas from OG presented a higher percentage of circulating macrophages, endothelial progenitor cells, HSC, and progenitor cells. No difference was detected in the percentage of neutrophil granulocytes and total leukocytes or in the proliferation of total cells, HSC, or total leukocytes. With regard to liver analysis of the OG group, there was a significant increase in circulating macrophages, primitive HSC, and oval cells but no difference in hematopoietic progenitor cells, total leukocytes, or leukocyte or total cell proliferation.
Unregulated maternal metabolism can affect hematopoietic populations within the placenta and fetal liver.
肥胖成年小鼠的骨髓细胞(BMC)显示出比增殖更高的凋亡率。造血干细胞(HSC)形成所有血细胞,是细胞治疗中重要的 BMC。由于已知产前发育可能受到母体代谢表观遗传编程的不利影响,因此本研究旨在调查母体超重对胎盘和胎儿肝脏造血龛的影响。
通过哺乳期过度喂养诱导雌性小鼠超重。在瑞士雌性与健康雄性交配后,分析 19 天妊娠龄(受孕后)的胎儿和胎盘。比较母体生物计量参数,并通过流式细胞术分析分离胎盘和胎儿肝脏细胞中的造血情况。还研究了胎盘形态和蛋白质含量。
该模型诱导了脂肪组织堆积、体重增加和母体高血糖。过度喂养组(OG)的胎盘显示出改变的形态、更高的碳水化合物和脂质沉积以及纤维连接蛋白和 PGC-1α 的蛋白质含量增加。细胞计量分析显示,OG 组的胎盘有更高比例的循环巨噬细胞、内皮祖细胞、HSC 和祖细胞。中性粒细胞粒细胞和总白细胞的百分比、总细胞、HSC 或总白细胞的增殖没有差异。关于 OG 组肝脏分析,循环巨噬细胞、原始 HSC 和卵圆细胞显著增加,但造血祖细胞、总白细胞或白细胞或总细胞增殖没有差异。
不受调节的母体代谢会影响胎盘和胎儿肝脏中的造血群体。