Cytological localization of chorionic gonadotropin alpha and placental lactogen mRNAs during development of the human placenta.

Hoshina, M; Boothby, Mark; Boime, Irving

doi:10.1083/jcb.93.1.190

Cited by 169 publications

(65 citation statements)

References 28 publications

(19 reference statements)

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“…Our immunohistochemical data show that the syncytial areas both in situ and when dissociated lacked appreciable staining for HLA-G, but were positive for ERVW-1. The appearance of CGA preceded CGB, and its initial synthesis may, as originally predicted by others (35), be initiated before syncytium formation even begins, whereas CGB may be a feature of a mature syncytium. Of particular interest to us was the localization of GABRP, a protein whose presence seems to foreshadow syncytium formation (SI Appendix, Fig.…”

Section: Discussionsupporting

confidence: 60%

Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas

Yabe

Alexenko

Amita

et al. 2016

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

135

148

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Human embryonic stem cells (ESCs) readily commit to the trophoblast lineage after exposure to bone morphogenetic protein-4 (BMP-4) and two small compounds, an activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83-01/PD173074; BAP treatment). During differentiation, areas emerge within the colonies with the biochemical and morphological features of syncytiotrophoblast (STB). Relatively pure fractions of mononucleated cytotrophoblast (CTB) and larger syncytial sheets displaying the expected markers of STB can be obtained by differential filtration of dispersed colonies through nylon strainers. RNA-seq analysis of these fractions has allowed them to be compared with cytotrophoblasts isolated from term placentas before and after such cells had formed syncytia. Although it is clear from extensive gene marker analysis that both ESC-and placenta-derived syncytial cells are trophoblast, each with the potential to transport a wide range of solutes and synthesize placental hormones, their transcriptome profiles are sufficiently dissimilar to suggest that the two cell types have distinct pedigrees and represent functionally different kinds of STB. We propose that the STB generated from human ESCs represents the primitive syncytium encountered in early pregnancy soon after the human trophoblast invades into the uterine wall.is encountered during at least two stages of human placental development (1-3). The first coincides with early implantation when a multinucleated syncytium forms, presumably by cell fusion events, ahead of proliferating, mononucleated, cytotrophoblast (CTB) cells originating from polar trophectoderm (3,4). This invasive syncytium emerges either during or soon after the trophoblast passes through the breached uterine epithelium and into the decidualized stromal layer beneath and appears to be responsible for hollowing out regions within the stroma to form lacunae (5), which become filled with fluid and cells from maternal blood and uterine glands and presumably provide a source of nutrients for the conceptus (3, 6). By about 12 d of gestation, soon after the blastocyst has sunk below the endometrial surface, strands of cytotrophoblast begin to form and penetrate through the primitive syncytium to form primary chorionic villi, which are subsequently invaded by extraembryonic mesoderm to form secondary and tertiary villi (villous trees) (2-4). The cytotrophoblast cells associated with the villi continue to divide and provide a progenitor cell population for the villous STB, which is the cell layer that covers the outer surface of the villi and forms the definitive interface involved in exchange of gases, nutrients, and excretory materials between the fetal placenta and maternal blood. Villous STB is also the major site for production of placental hormones. Cytotrophoblast cells at the tips of the anchoring villi proliferate and colonize the endometrium, thus expanding the placental bed and simultaneously remodeling maternal spiral arteries. The extent to which extravillous trophoblast becom...

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Section: Discussionsupporting

confidence: 60%

Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas

Yabe

Alexenko

Amita

et al. 2016

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

135

148

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“…Transcripts for the third member of the TAM trio, namely MERTK, are also expressed in the differentiated ESC. At d 4 of differentiation, the time the cultures were exposed to ZIKV, MERTK, like TYRO3, is most concentrated in areas positive for the α-subunit of hCG, CGA, which is a marker that predicts future STB (32,64) (Fig. 2), and, as discussed above, STB seems to be the most immediate target for cellular destruction in infected colonies.…”

Section: Release Of Infection-competent Virus By Esc and Esc-derived mentioning

confidence: 81%

Vulnerability of primitive human placental trophoblast to Zika virus

Sheridan

Yunusov

Balaraman

et al. 2017

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

155

150

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Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKVU) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKVC). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction.

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“…These data were confirmed in vitro using invasive EVCT primary cultures obtained from first trimester human placentas. Indeed, in contrast with the well-established in vivo (25) and in vitro hCG expression in villous trophoblast (16,26,27), the presence of hCG in EVCT has been investigated only by immunohistochemistry and results remained controversial. Although Gosseye and Fox have never detected this hormone in EVCT irrespective of the term studied (19), other authors have shown positive staining in different sub-types of EVCT.…”

Section: Discussionmentioning

confidence: 99%

Human Chorionic Gonadotropin Expression in Human Trophoblasts from Early Placenta: Comparative Study Between Villous and Extravillous Trophoblastic Cells

Handschuh¹,

Gadrey²,

Tsatsaris³

et al. 2007

Placenta

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Human trophoblast differentiates into two pathways: extravillous cytotrophoblasts (EVCT) that invade the uterus wall and villous cytotrophoblasts (VCT) that fuse to form the syncytiotrophoblast (ST) involved in placental exchanges and endocrine function. It is established that hCG is produced and secreted by the ST into the maternal compartment where it plays a key endocrine role and stimulates ST formation in an autocrine manner. Herein, we investigated hCG expression in early placentas by immunohistochemistry using different antibodies. We then compared hCG secretion by primary cultures of VCT and EVCT isolated from the same first trimester human chorionic villi. In situ hCG was immunodetected in EVCT all along their invasive differentiating pathway excepted in cells near the stromal core of the proximal column. hCG expression was confirmed in vitro by immunocytochemistry and hCG secretion quantified in cell supernatants. Interestingly, whereas hCG secretion increased during VCT differentiation into ST (from 60 to 350 UI/L/µg DNA), EVCT secretion remained constant and at a high level during the same culture period (160 UI/L/µg DNA). Our data demonstrated that in addition to the ST, invasive EVCT also expressed and secreted high levels of hCG, suggesting a specific paracrine and/or autocrine role for hCG from EVCT origin.3

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Cytological localization of chorionic gonadotropin alpha and placental lactogen mRNAs during development of the human placenta.

Cited by 169 publications

References 28 publications

Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas

Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas

Vulnerability of primitive human placental trophoblast to Zika virus

Human Chorionic Gonadotropin Expression in Human Trophoblasts from Early Placenta: Comparative Study Between Villous and Extravillous Trophoblastic Cells

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