Protection of Lycopene against Embryonic Anomalies and Yolk Sac Placental Vasculogenic Disorders Induced by Nicotine Exposure

Identification of a new agent from natural products for the protection of embryonic anomalies is potentially valuable. To investigate the protective effect exerted by lycopene against nicotine-induced malformations, mouse embryos in embryonic day 8.5 with yolk sac placentas were cocultured with 1 mM nicotine and/or lycopene (1×10−6, 1×10−5 μM) for 48 h. The morphological defects and apoptotic cell deaths in the embryo and yolk sac placenta of the nicotine group were significantly increased. Exposure to nicotine resulted in reduced superoxide dismutase (SOD) activity and cytoplasmic SOD and cytoplasmic glutathione peroxidase mRNA levels, but increased lipid peroxidation level in embryos. Moreover, treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. However, all the parameters were significantly improved by treatment with lycopene, as compared to the nicotine group. These findings indicate the potential of lycopene as a protective agent against embryonic anomalies and yolk sac vasculogenic and placenta-forming defects induced by nicotine through modulations of oxidative, apoptotic, vasculogenic, and inflammatory activities.

Evolution of placentotrophy: using viviparous sharks as a model to understand vertebrate placental evolution

Reproducing sharks must provide their offspring with an adequate supply of nutrients to complete embryonic development. In oviparous (egg-laying) sharks, offspring develop outside the mother, and all the nutrients required for embryonic growth are contained in the egg yolk. Conversely, in viviparous (live-bearing) sharks, embryonic development is completed inside the mother, providing offspring with the opportunity to receive supplementary embryonic nourishment, known as matrotrophy. Viviparous sharks exhibit nearly all forms of matrotrophy known in vertebrates, including a yolk-sac placenta, which involves several significant ontogenetic modifications to fetal and maternal tissues. The selective pressures that have driven the evolution of complex placentas in some shark species, but not in others, are unresolved. Herein we review the mechanisms of reproductive allocation and placental diversity in sharks, and consider the application of both adaptive and conflict hypotheses for the evolution of placental nutrient provisioning. Both have likely played roles in placental evolution in sharks, perhaps at different times in evolutionary history. Finally, we recommend sharks as an outstanding model system to investigate the evolution of placentas and mechanisms for fetal nutrition during pregnancy in vertebrates.

Abstract 81: Hemogenic Endocardium Contributes to Cardiac Tissue Macrophages

Transient phase of hematopoiesis in mammalian embryo occur in multiple anatomical sites including yolk-sac, placenta and the aorta-gonad-mesonephros region. A recent report demonstrates that endocardium also contribute to definitive hematopoiesis during embryogenesis. CD41+ hemogenic endocardial cells are enriched in the endocardial cushion in the outflow tract and atrial-ventricular canal at around embryonic day 9.5-11.5. Here we show the hemogenic endocardium as a novel source of cardiac tissue macrophages (cTMs). The fate of endocardial cells were traced using nuclear factor of activated T-cells 1 (Nfatc1)-cre mouse line, a Cre driver specific to the endocardium. Flow-cytometry study using NFATc1 cre/+ ; R26YFP reporter/+ with CD45, CD11b and F4/80 demonstrated that endocardially-derived cardiac tissue macrophages (EcTMs) were found in the heart from embryonic day 10.5 to adult stages. The number of EcTMs gradually expanded from embryonic day 15.5 to postnatal 8 and were maintained until adult stage. Immunofluorescent staining with CD68, F4/80 and CD206 revealed that EcTMs were identified in the cardiac cushion at embryonic day 13.5 and 15.5, and persisted in the valve mesenchyme and atria after birth. To assess their functional potential, we characterized their M1/M2 polarity. Surface marker analyses indicate that EcTMs in embryo were classified exclusively as M2 type whereas non-endocardially-derived cTMs (non-EcTMs) contributed to both M1 and M2 type. EcTMs in postnatal hearts were also predominantly M2 type. Genome-wide transcriptome analysis showed that genes related to antigen presenting and phagocytosis were significantly more upregulated in EcTMs compared to non-EcTMs. These findings indicate that the hemogenic endocardium contributes to M2-type cTMs in endocardial cushion and valve mesenchyme throughout embryogenesis and postnatal heart. Cardiac tissue macrophages migrate to the heart in multiple waves including postnatal bone marrow, fetal liver during embryonic stages, and possibly yolk sac prior to the liver colonization. Our results suggest that the 4 th population of macrophages originate directly from the local hemogenic endocardium.

Hemogenic endothelium during development and beyond

During embryonic development, multilineage HSCs/progenitor cells are derived from specialized endothelial cells, termed hemogenic endothelium, within the yolk sac, placenta, and aorta. Whether hemogenic endothelial cells contribute to blood cell development at other sites of definitive hematopoiesis, such as in the fetal liver and fetal bone marrow, is not known. Also unknown is whether such cells exist within the vasculature of adult bone marrow and generate hematopoietic stem cells after birth. These issues and their clinical relevance are discussed herein.