RESUMO
Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Feto/citologia , Feto/metabolismo , Células Germinativas/citologia , Ovário/citologia , Ovário/metabolismo , Apoptose/genética , Apoptose/fisiologia , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proliferação de Células , Feminino , Imunofluorescência , Células Germinativas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Fator de Transcrição MSX1/genética , Fator de Transcrição MSX1/metabolismo , Ovário/embriologia , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Técnicas de Cultura de TecidosRESUMO
OBJECTIVE: There are a number of cardiac output (CO) monitors that could potentially be used in the ED. Two of the most promising methods, thoracic electrical bioimpedance and suprasternal Doppler, have not been directly compared. The aim of this study was to investigate the feasibility of CO monitoring using suprasternal Doppler and bioimpedance in emergency care and compare haemodynamic data obtained from both monitors. METHODS: Haemodynamic measurements were made on the same group of patients using bioimpedance (Niccomo, Medis, Germany) and suprasternal Doppler (USCOM, Sydney, Australia). RESULTS: Usable CO data were obtained in 97% of patients by suprasternal Doppler and 87% by bioimpedance. The median CO obtained by Doppler was 3.4 L/min lower than bioimpedance. The stroke volume median was lower by 51 mL in Doppler. CONCLUSIONS: These two methods of non-invasive cardiac monitoring are not interchangeable. The results suggest that the choice of non-invasive cardiac monitor is important, but the grounds on which to make this choice are not currently clear.