Talk:Trophoblast

Development and function of trophoblast giant cells in the rodent placenta

Int J Dev Biol. 2010;54(2-3):341-54.

Hu D, Cross JC.

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine and Graduate Program in Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada. Abstract Trophoblast giant cells (TGCs) are the first cell type to terminally differentiate during embryogenesis and are of vital importance for implantation and modulation of post-implantation placentation. TGCs are mononuclear and polyploid but are heterogenous and dynamic. At least four different subtypes of TGCs are present within the mature placenta that have distinct cell lineage origins. The development of TGCs is complex and requires transition from the mitotic to the endoreduplication cell cycle and is regulated by a wide variety of factors. During early gestation, TGCs mediate blastocyst attachment and invasion into the uterine epithelium, regulate uterus decidualization, and anatomosis with maternal blood spaces to form the transient yolk sac placenta. During later gestation, TGCs secrete a wide array of hormones and paracrine factors, including steroid hormones and Prolactin-related cytokines, to target the maternal physiological systems for proper maternal adaptations to pregnancy and the fetal-maternal interface to ensure vasculature remodeling. The large number of mouse mutants with defects in TGC development and function are giving us significant new insights into the biology of these fascinating cells.

PMID: 19876834 http://www.ncbi.nlm.nih.gov/pubmed/19876834

http://www.ijdb.ehu.es/web/paper.php?doi=10.1387/ijdb.082768dh

Int J Dev Biol.

Vol. 54 Nos. 2/3 (2010) Placenta

http://www.ijdb.ehu.es/web/contents.php?vol=54&issue=2-3

Function of caspase-14 in trophoblast differentiation

Reprod Biol Endocrinol. 2009 Sep 14;7:98.

White LJ, Declercq W, Arfuso F, Charles AK, Dharmarajan AM.

School of Anatomy and Human Biology, Faculty of Life and Physical Sciences, The University of Western Australia, Perth, Western Australia, Australia. yornup@gmail.com Abstract BACKGROUND: Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored.

METHODS: Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways.

RESULTS: Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted.

CONCLUSION: Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

PMID: 19747408

Intrauterine fate of invasive trophoblast cells

Placenta. 2009 May;30(5):457-63. Epub 2009 Apr 2.

Rosario GX, Ain R, Konno T, Soares MJ.

Institute of Maternal-Fetal Biology, Division of Cancer and Developmental Biology, Department of Pathology and Laboratory of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. Abstract Invasion of trophoblast cells into the uterine spiral arteries and the uterine wall is characteristic of hemochorial placentation. In the rat, trophoblast cells penetrate through the uterine decidua and well into the metrial gland. In this report, we examined the fate of these invasive trophoblast cells following parturition. Invasive trophoblast endocrine cells were retained in the postpartum mesometrial uterus in the rat. The demise of invasive trophoblast cells was followed by the appearance of differentiated smooth muscle cells surrounding blood vessels previously lined by invasive trophoblast cells and an infiltration of macrophages. Regulation of intrauterine trophoblast cell fate was investigated following premature removal of the fetus or removal of the fetus and chorioallantoic placenta. The presence of the fetus affected the distribution of invasive trophoblast cells within the uterus but did not negatively impact their survival. Premature removal of all chorioallantoic placentas and associated fetuses from a uterus resulted in extensive removal of intrauterine trophoblast cells. In summary, the postpartum demise of intrauterine invasive trophoblast cells is a dynamic developmental event regulated in part by the removal of trophic signals emanating from the chorioallantoic placenta.

PMID: 19344949

Trophoblast infection with Chlamydia pneumoniae and adverse pregnancy outcomes associated with placental dysfunction

Am J Obstet Gynecol. 2009 May;200(5):526.e1-7.

Gomez LM, Parry S.

Maternal and Child Research Program, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Abstract OBJECTIVE: We sought to determine whether Chlamydia pneumoniae impairs invasive trophoblast function and is associated with preeclampsia.

STUDY DESIGN: We conducted cell viability and invasion assays using primary extravillous trophoblast cells isolated from first-trimester placentas. We performed a case-control study to identify C pneumoniae in trophoblast cells dissected by laser capture microscopy from placentas in women with severe preeclampsia and control subjects who delivered at term.

RESULTS: Trophoblast cell viability and invasion through extracellular matrices were decreased after infection with C pneumoniae (both P < .05). C pneumoniae DNA was detected in trophoblast cells in 15/48 cases but only 3/30 controls (odds ratio, 4.1; P = .02). Positive and negative controls yielded expected results.

CONCLUSION: C pneumoniae infection can reduce trophoblast invasion into the uterine wall and is associated with preeclampsia. Further investigation of the mechanisms by which C pneumoniae induces trophoblast dysfunction, and the identification of therapies to prevent adverse outcomes attributed to trophoblast dysfunction, are warranted.

PMID: 19375572 http://www.ncbi.nlm.nih.gov/pubmed/19375572

Chlamydophila pneumoniae is a species of Chlamydophila bacteria that infects humans and is a major cause of pneumonia.

While dysferlin and myoferlin are coexpressed in the human placenta, only dysferlin expression is responsive to trophoblast fusion in model systems

Biol Reprod. 2009 Jul;81(1):33-9. Epub 2009 Feb 18. Robinson JM, Ackerman WE 4th, Behrendt NJ, Vandre DD.

Departments of Physiology and Cell Biology and Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA. robinson.21@osu.edu Abstract The syncytiotrophoblast is a specialized epithelium derived from mononuclear cytotrophoblasts that fuse to form this extensive syncytium. Dysferlin is expressed primarily in the apical plasma membrane of the syncytiotrophoblast in the human placenta. Here, we document the presence of another member of the ferlin family, myoferlin, in the placenta and show that it too is expressed primarily in the syncytiotrophoblast. Additionally, we examined the trophoblastic cell lines BeWo, JAR, and JEG-3 for the expression of dysferlin and myoferlin and determined the extent to which their expression was modulated by cell-cell fusion. In trophoblastic cells, there was a positive correlation between cell fusion and increased dysferlin expression but not myoferlin expression. Regarding expression, these trophoblastic cell lines recapitulate the distribution of dysferlin in mononuclear cytotrophoblasts and the syncytiotrophoblast in vivo.

PMID: 19228595 http://www.ncbi.nlm.nih.gov/pubmed/19228595

HOXA13 Is essential for placental vascular patterning and labyrinth endothelial specification

PLoS Genet. 2008 May 16;4(5):e1000073.

Shaut CA, Keene DR, Sorensen LK, Li DY, Stadler HS.

Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, United States of America. Abstract In eutherian mammals, embryonic growth and survival is dependent on the formation of the placenta, an organ that facilitates the efficient exchange of oxygen, nutrients, and metabolic waste between the maternal and fetal blood supplies. Key to the placenta's function is the formation of its vascular labyrinth, a series of finely branched vessels whose molecular ontogeny remains largely undefined. In this report, we demonstrate that HOXA13 plays an essential role in labyrinth vessel formation. In the absence of HOXA13 function, placental endothelial cell morphology is altered, causing a loss in vessel wall integrity, edema of the embryonic blood vessels, and mid-gestational lethality. Microarray analysis of wild-type and mutant placentas revealed significant changes in endothelial gene expression profiles. Notably, pro-vascular genes, including Tie2 and Foxf1, exhibited reduced expression in the mutant endothelia, which also exhibited elevated expression of genes normally expressed in lymphatic or sinusoidal endothelia. ChIP analysis of HOXA13-DNA complexes in the placenta confirmed that HOXA13 binds the Tie2 and Foxf1 promoters in vivo. In vitro, HOXA13 binds sequences present in the Tie2 and Foxf1 promoters with high affinity (K(d) = 27-42 nM) and HOXA13 can use these bound promoter regions to direct gene expression. Taken together, these findings demonstrate that HOXA13 directly regulates Tie2 and Foxf1 in the placental labyrinth endothelia, providing a functional explanation for the mid-gestational lethality exhibited by Hoxa13 mutant embryos as well as a novel transcriptional program necessary for the specification of the labyrinth vascular endothelia.

PMID: 18483557