The placenta provides the physiological interface between mother and fetus and is critically involved in controlling the environment directing the development of the fetus. Trophoblast cells, the parenchymal cells of the placenta, form the framework of the gestational conduit that delivers resources to the fetus. Disruptions in the development of trophoblast cells result in retardation in the growth and maturation of the fetus. The objectives of this project are to understand control mechanisms involved in regulating trophoblast cell differentiation. In this proposal, our focus is directed towards identifying the regulatory mechanisms involved in identifying signaling pathways arising from the cell surface to the nucleus that are responsible for the development of trophoblast giant cells. Proposed studies utilize the rat chorioallantoic placenta and in vitro rat trophoblast cell culture systems. Two major specific aims, formulated as questions, are addressed in this research: 1) What is the nature of the intracellular signaling pathways involved in the control of trophoblast giant cell differentiation? 2) Is there a link between trans- acting factors and cis-elements controlling trophoblast giant cell- specific gene expression and the signaling pathways implicated in trophoblast giant cell differentiation? The experimentation utilizes molecular biology, protein chemistry, immunochemistry, and various cell biology and cell culture techniques. Identification of regulatory mechanisms controlling trophoblast cell differentiation will provide a better understanding of placental development and an avenue into the etiology of early pregnancy loss and various disorders and neoplasms of the placenta.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020676-11
Application #
2655110
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1986-07-01
Project End
2000-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Kansas
Department
Physiology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Soares, Michael J; Varberg, Kaela M; Iqbal, Khursheed (2018) Hemochorial placentation: development, function, and adaptations. Biol Reprod 99:196-211
Bu, Pengli; Yagi, Shintaro; Shiota, Kunio et al. (2017) Origin of a rapidly evolving homeostatic control system programming testis function. J Endocrinol 234:217-232
Chakraborty, Damayanti; Muto, Masanaga; Soares, Michael J (2017) Ex vivo Trophoblast-specific Genetic Manipulation Using Lentiviral Delivery. Bio Protoc 7:
Aplin, John D; Beristain, Alexander; DaSilva-Arnold, Sonia et al. (2017) IFPA meeting 2016 workshop report III: Decidua-trophoblast interactions; trophoblast implantation and invasion; immunology at the maternal-fetal interface; placental inflammation. Placenta 60 Suppl 1:S15-S19
Dhakal, Pramod; Soares, Michael J (2017) Single-step PCR-based genetic sex determination of rat tissues and cells. Biotechniques 62:232-233
Soares, Michael J; Iqbal, Khursheed; Kozai, Keisuke (2017) Hypoxia and Placental Development. Birth Defects Res 109:1309-1329
Renaud, Stephen J; Scott, Regan L; Chakraborty, Damayanti et al. (2017) Natural killer-cell deficiency alters placental development in rats. Biol Reprod 96:145-158
Soares, Michael J; Vivian, Jay L (2016) Tipping the balance toward trophoblast development. Proc Natl Acad Sci U S A 113:5144-6
Bu, Pengli; Alam, Sheikh M Khorshed; Dhakal, Pramod et al. (2016) A Prolactin Family Paralog Regulates Placental Adaptations to a Physiological Stressor. Biol Reprod 94:107
Imakawa, Kazuhiko; Dhakal, Pramod; Kubota, Kaiyu et al. (2016) CITED2 modulation of trophoblast cell differentiation: insights from global transcriptome analysis. Reproduction 151:509-16

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