Placenta: The Forgotten Organ

Maltepe, Emin; Fisher, Susan J.

doi:10.1146/annurev-cellbio-100814-125620

Cited by 409 publications

(337 citation statements)

References 248 publications

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“…Preeclampsia is a multifaceted disease that can be associated with placental hypoxia and a failure of trophoblast-directed uterine spiral artery remodeling (3)(4)(5)(44)(45)(46). Analyses of placental tissue from preterm and term controls, intrauterine growth restriction, and preeclamptic pregnancies indicated that KDM3A expression was up-regulated in preeclampsia (Fig.…”

Section: Kdm3a and Mmp12 Expression In Diseased Human Placental Tissuesmentioning

confidence: 99%

“…placenta | hypoxia | trophoblast invasion | epigenetics | plasticity V ascular remodeling is an important pregnancy-associated adaptation in hemochorial placentation and is orchestrated, in part, from the contributions of invasive trophoblast cells (also termed extravillous trophoblast) (1)(2)(3). These cells invade into the uterus and restructure spiral arteries turning them into flaccid low resistance vessels facilitating the flow of maternal resources to the placenta and then to the fetus.…”

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“…These cells invade into the uterus and restructure spiral arteries turning them into flaccid low resistance vessels facilitating the flow of maternal resources to the placenta and then to the fetus. Failure of trophoblast cell invasion and vascular remodeling is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth (3)(4)(5). Invasive trophoblast cells arise from trophoblast stem (TS)/progenitor cell populations and can be classified based on their entry into the uterine parenchyma (5,6).…”

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confidence: 99%

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HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia

Chakraborty

Cui

Rosario

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

101

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The hemochorial placenta develops from the coordinated multilineage differentiation of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth. Hypoxia plays an instructive role in influencing trophoblast cell differentiation and regulating placental organization. Key downstream hypoxia-activated events were delineated using rat TS cells and tested in vivo, using trophoblast-specific lentiviral gene delivery and genome editing. DNA microarray analyses performed on rat TS cells exposed to ambient or low oxygen and pregnant rats exposed to ambient or hypoxic conditions showed up-regulation of genes characteristic of an invasive/ vascular remodeling/inflammatory phenotype. Among the shared up-regulated genes was matrix metallopeptidase 12 (MMP12). To explore the functional importance of MMP12 in trophoblast celldirected spiral artery remodeling, we generated an Mmp12 mutant rat model using transcription activator-like nucleases-mediated genome editing. Homozygous mutant placentation sites showed decreased hypoxia-dependent endovascular trophoblast invasion and impaired trophoblast-directed spiral artery remodeling. A link was established between hypoxia/HIF and MMP12; however, evidence did not support Mmp12 as a direct target of HIF action. Lysine demethylase 3A (KDM3A) was identified as mediator of hypoxia/HIF regulation of Mmp12. Knockdown of KDM3A in rat TS cells inhibited the expression of a subset of the hypoxia-hypoxia inducible factor (HIF)-dependent transcripts, including Mmp12, altered H3K9 methylation status, and decreased hypoxia-induced trophoblast cell invasion in vitro and in vivo. The hypoxia-HIF-KDM3A-MMP12 regulatory circuit is conserved and facilitates placental adaptations to environmental challenges. placenta | hypoxia | trophoblast invasion | epigenetics | plasticity

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Section: Kdm3a and Mmp12 Expression In Diseased Human Placental Tissuesmentioning

confidence: 99%

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confidence: 99%

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HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia

Chakraborty

Cui

Rosario

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

101

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“…No solo el desarrollo placentario tiene efecto a corto plazo en la salud de un individuo; hoy en día, se reconoce el papel de la epigenética dentro del proceso salud o enfermedad a largo plazo en las poblaciones humanas (18). Las alteraciones del desarrollo de la placenta se asocian con enfermedades como la preeclampsia y el retardo del crecimiento intrauterino (19,20).La inadecuada invasión uterina trofoblástica, la alteración de las modificaciones en las arterias espirales y las anomalías en el desarrollo de las vellosidades corióni-cas, hacen parte de la fisiopatología de la preeclampsia y del retardo del crecimiento intrauterino (21,22). Las condiciones medioambientales maternas pueden predisponer a enfermedades de su descendencia en la vida adulta mediante procesos epigenéticos y programación fetal; actualmente, se considera el periodo de los primeros mil días de vida (desde el útero hasta …”

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Investigación en salud materno-perinatal

Montealegre-Páez

García-Robles

2018

Rev. salud. bosque.

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ResumenLa salud materno-perinatal es un área de interés en la investigación en salud y un reto en la práctica médica. La reducción de la mortalidad y de la morbilidad materna y en la población pediátrica es un problema de salud pública en nuestro país, fue uno de los objetivos del desarrollo del milenio y, actualmente, es parte de los objetivos de desarrollo sostenible de las Naciones Unidas.Por esta razón, surge la necesidad de profundizar en el tema y comprender los factores que influyen en las complicaciones del embarazo, la salud del recién nacido y los posibles desenlaces adversos de la gestación.Colombia ha estado siempre comprometida en reducir las cifras de mortalidad materna e infantil, implementando el desarrollo y la aplicación de guías de práctica clínica y protocolos de atención.Palabras clave: salud materna, embarazo, salud pública, mortalidad materna, mortalidad perinatal.Keywords: Maternal health, pregnancy, public health, maternal mortality, perinatal mortality. AbstractPerinatal and maternal health has been a subject of interest in health research and a challenge in medical practice. Decreasing maternal and perinatal mortality and morbidity is an important public health problem in our country that was part of the Millennium Development Goals and currently is part of the Sustainable Development Goals of the United Nations. For this reason, further research on this topic is needed specifically on understanding the factors that influence pregnancy complications, the health of the newborn and the possible outcomes of pregnancy. Colombia has always been committed to reducing maternal and infant mortality, implementing and enforcing clinical practice guidelines and protocols.Págs. ResumoA saúde materna perinatal é uma área de interesse da pesquisa em saúde e um desafio na prática médica. Diminuir a mortalidade e morbilidade materna e da população pediátrica é um problema de saúde pública no nosso país que foi um dos objetivos de Desenvolvimento do Milênio e atualmente faz parte dos objetivos de desenvolvimento sustentável das Nações Unidas. Por esse motivo surge a necessidade de aprofundar no tema e compreender os fatores que influem nas complicações da gravidez e na boa saúde do recém-nascido, mesmo como nos possíveis desenlaces adversos da gestação. Colômbia tem estado sempre comprometida com a redução das cifras de mortalidade materna e infantil, implementando as guias de prática clínica e protocolos de atenção.Palavras chave: saúde materna, gravidez, mortalidade materna, mortalidade perinatal IntroducciónLa investigación en salud ha sido una de las grandes herramientas a la hora de proponer políticas en salud y mejorar la calidad de vida de las personas. Es por esta razón que, en la actualidad, muchas instituciones de salud y de educación superior aúnan esfuerzos para indagar en los aspectos que más afectan y preocupan a sus poblaciones. Con base en los resultados de dichas investigaciones, los profesionales de la salud se ven en la capacidad de proporcionar diagnósticos más certeros y mejores a...

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“…Yabe et al (9) took advantage of a specialized property of one type of differentiated trophoblast cell that arises through the fusion of progenitors generating multinucleated cells referred to as syncytiotrophoblasts. These cells are known to possess a range of specific functions, including hormonogenesis and bidirectional solute transport, features vital to the placenta and essential for in utero growth and survival of the fetus (12). In the PNAS report, human ES cells were treated with the BAP mixture for 8 d, dissociated, and then passed through nylon cell strainers of different pore sizes to fractionate cells on the basis of size.…”

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confidence: 99%