Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys

Zhou, Yan; Chiu, King; Brescia, Robert; Combs, C. Andrew; Katz, Michael L.; Kitzmiller, John L.; Heilbron, David C.; Fisher, Susan J.

doi:10.1016/0002-9378(93)90172-f

Cited by 65 publications

(34 citation statements)

References 16 publications

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“…Hypoxia signaling regulates the development of the invasive trophoblast cell lineage and uterine spiral artery remodeling (13)(14)(15)(16). As a first step toward identifying potential adaptive mechanisms downstream of hypoxia exposure, we profiled transcriptomes of rat TS cells (32) exposed to low oxygen and placentation sites from rats exposed to hypoxic conditions using DNA microarray technology (Gene Expression Omnibus repository: GSE80339 and GSE80340; www.ncbi.nlm.nih.gov/geo/).…”

Section: Resultsmentioning

confidence: 99%

“…As in other tissues, low oxygen is a potent driver of vascular development at the maternal-fetal interface. Hypoxia exposure can redirect placental organization and promote development of the invasive trophoblast cell lineage and uterine spiral artery remodeling, representing adaptive responses conserved in the rat, monkey, and human (13)(14)(15)(16). Cellular responses to oxygen deficits are mediated by hypoxia inducible factor (HIF), a transcription factor consisting of a heterodimer composed of oxygen sensitive…”

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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.

100

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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: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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.

100

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“…This is a conserved adaptive response. Maternal anemia (human) and chronic constriction of the lower aorta (rhesus monkey), which lead to hypoxia at the maternal-fetal interface, are also triggers for increasing intrauterine trophoblast invasion (20,21).…”

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confidence: 99%

Natural killer cells direct hemochorial placentation by regulating hypoxia-inducible factor dependent trophoblast lineage decisions

Chakraborty

Rumi

Konno

et al. 2011

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

150

202

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Natural killer (NK) cells are recruited into the uterine stroma during establishment of the hemochorial placenta and are proposed regulators of uterine spiral artery remodeling. Failures in uterine spiral artery remodeling are linked to diseases of pregnancy. This prompted an investigation of the involvement of NK cells in placentation. NK cell depletion decreased the delivery of proangiogenic factors and delayed uterine spiral artery development, leading to decreased oxygen tension at the placentation site, stabilized hypoxia-inducible factor 1A protein, and redirected trophoblast differentiation to an invasive phenotype. Trophoblast cells replaced the endothelium of uterine spiral arteries extending the depth of the placental vascular bed and accelerating vessel remodeling. Hypoxia-regulated trophoblast lineage decisions, including expansion of invasive trophoblast, could be reproduced in vitro by using rat trophoblast stem cells and were dependent on hypoxia-inducible factor signaling. We conclude that NK cells guide hemochorial placentation through controlling a hypoxiasensitive adaptive reflex regulating trophoblast lineage decisions.

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“…Most of the pregnant monkeys became hypertensive. However, Zhou et al 34 also reported an increased depth of decidual, vascular, and myometrial trophoblast invasion, which contrasts to women with preeclampsia in whom uteroplacental ischemia is associated with shallow trophoblast invasion resulting in the failed dilation of the spiral arteries. 35 In pregnant primates (Papio anubis), approximately 60% reduction of aortic flow on day 100 of the 160 days of pregnancy resulted in an approximately 30% increase in BP at term (measured under anesthesia), while renal vascular resistance also was increased.…”

Section: The Uteroplacental Ischemia Model Of Preeclampsiamentioning

confidence: 88%

“…31 Studies in the rhesus monkey 32 suggested that BP increased after reductions in uteroplacental perfusion pressure although only one sham-operated control was studied. Combs et al 33 and Zhou et al 34 made longitudinal measurements of BP in the conscious, chronically instrumented rhesus monkey, for 4 weeks after reduction of the uterine perfusion pressure in late pregnancy. Most of the pregnant monkeys became hypertensive.…”

Section: The Uteroplacental Ischemia Model Of Preeclampsiamentioning

confidence: 99%

Animal models of preeclampsia

Podjarny

Losonczy

Baylis

2004

Seminars in Nephrology

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Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys

Cited by 65 publications

References 16 publications

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

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

Natural killer cells direct hemochorial placentation by regulating hypoxia-inducible factor dependent trophoblast lineage decisions

Animal models of preeclampsia

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