Hematopoietic changes in the offspring induced by maternal overweight: Effect on placenta and fetal liver populations.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: Unregulated maternal metabolism can affect hematopoietic populations within the placenta and fetal liver.