Successful embryonic development within the female reproductive tract requires the generation of a specialized maternal structure, the decidua. Decidual cells are located at the interface separating invading trophoblast cells from the maternal environment and represent the initial maternal response and adaptation to intrauterine embryonic development. Decidual cells contribute to the establishment and maintenance of pregnancy through their production of secretory products related to anterior pituitary prolactin (PRL). Failure of normal decidual cell maturation may result in early pregnancy loss, uncontrolled trophoblast cell growth and invasion, immunologic rejection of the embryo, embryonic growth retardation or embryonic/fetal death. The overall objective of this research is to understand the involvement of the decidual cell signaling system in the establishment and maintenance of pregnancy. The proposal focuses on decidual signals related to pituitary PRL. This hormone has been implicated in directing the early changes in ovarian and uterine function required for the establishment of pregnancy. Our understanding of the role of this hormone in the establishment of pregnancy has been hindered because an animal model has not been adequately developed. We propose to remedy this situation by establishing the rat as a model for the study of decidual cell signaling.
Specific aims for this proposal include: 1) generation and characterization of recombinant decidual PRL-related protein (dPRP), 2) examination of the distribution of the dPRP in decidual tissues, 3) examination of the biological actions of the dPRP, and 4) characterization of the control of dPRP gene expression. The experiments are directed toward evaluating the nature of the signaling between the decidua and the corpus luteum and between the decidua and the developing placenta. The experimentation utilizes molecular biology, protein chemistry, immunochemistry, and various cell biology and cell culture techniques. The investigation promises to further our understanding of cellular and molecular processes involved in the establishment of pregnancy and our understanding of the chemistry and biology of an important class of regulatory hormones, PRLs. Availability of this knowledge will make possible the development of therapeutic strategies for effectively controlling the establishment of pregnancy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD029797-01A2
Application #
2202178
Study Section
Reproductive Biology Study Section (REB)
Project Start
1994-05-01
Project End
1999-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
1
Fiscal Year
1994
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
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Wiemers, Dustin O; Ain, Rupasri; Ohboshi, Shigeki et al. (2003) Migratory trophoblast cells express a newly identified member of the prolactin gene family. J Endocrinol 179:335-46
Dai, G; Wang, D; Liu, B et al. (2000) Three novel paralogs of the rodent prolactin gene family. J Endocrinol 166:63-75
Sahgal, N; Knipp, G T; Liu, B et al. (2000) Identification of two new nonclassical members of the rat prolactin family. J Mol Endocrinol 24:95-108
Wang, D; Ishimura, R; Walia, D S et al. (2000) Eosinophils are cellular targets of the novel uteroplacental heparin-binding cytokine decidual/trophoblast prolactin-related protein. J Endocrinol 167:15-28
Orwig, K E; Soares, M J (1999) Transcriptional activation of the decidual/trophoblast prolactin-related protein gene. Endocrinology 140:4032-9
Dai, G; Wolfe, M W; Soares, M J (1999) Distinct regulatory regions from the prolactin-like protein C variant promoter direct trophoblast giant cell versus spongiotrophoblast cell-specific expression. Endocrinology 140:4691-8
Dai, G; Chapman, B M; Wang, D et al. (1999) Prolactin-like protein-A gene structure and chromosomal mapping. Mamm Genome 10:78-80
Dai, G; Chapman, B M; Liu, B et al. (1998) A new member of the mouse prolactin (PRL)-like protein-C subfamily, PRL-like protein-C alpha: structure and expression. Endocrinology 139:5157-63
Muller, H; Dai, G; Soares, M J (1998) Placental lactogen-I (PL-I) target tissues identified with an alkaline phosphatase-PL-I fusion protein. J Histochem Cytochem 46:737-43

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