The mammalian uterus is essential for reproduction because it sustains the fertilized ovum, provides an environment suitable for implantation and nurtures the conceptus during early embryonic development and throughout gestation. Implantation per se is a complex and poorly understood reproductive process regulated by many factors including the ovarian steroids. It is possible that steroid-specific and/or stage- specific macromolecules play a key role in the establishment and maintenance of pregnancy. Thus, these macromolecules could potentially serve as markers for a uterus that is receptive to the implanting embryo. The overall objective of this proposal is to determine the regulation of previously identified proteins i.e., retinol binding protein (RBP) and insulin-like growth factor binding protein-1 (IGFBP-1), and two additional groups of P and hCG regulated proteins (Mr 40,000 and Mr 27,000-30,000) between days 7 and 14 post-ovulation (PO) in the pregnant and non-pregnant baboon uterus. Since our previous studies have shown that RBP and IGFBP-1 are regulated in a cell - and stage specific manner between 18 and 32 days PO, the proposed studies in the first specific aim will determine the biochemical, immunological and molecular regulation of these uterine proteins during the period of implantation in the baboon. The second specific aim will determine the effects of ovarian hyperstimulation by exogenous hormones and post-ovulatory inhibition of estrogen action on the expression of these macromolecules during implantation. finally, since growth factors are thought to regulate the action of ovarian steroids via paracrine and/or autocrine actions we propose to study the expression of insulin-like factor and epidermal growth factors and their respective receptors during implantation. The ultimate goal of these studies is to identify and biological significance of endometrial proteins in ensuring successful implantation and pregnancy. The data from the proposed studies should provide basic information on the physiology of the primate uterus and help improve our knowledge relating to implantation. These studies should be helpful to clinicians as they attempt to deal knowledgeably with the full spectrum of the reproductive process, namely conception, infertility and contraception.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD029964-03
Application #
2202340
Study Section
Special Emphasis Panel (SRC (02))
Project Start
1992-12-01
Project End
1996-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Banerjee, Prajna; Fazleabas, Asgerally T (2010) Endometrial responses to embryonic signals in the primate. Int J Dev Biol 54:295-302
Fazleabas, Asgerally T (2006) A baboon model for simulating pregnancy. Methods Mol Med 121:101-10
Julian, JoAnne; Enders, Allen C; Fazleabas, Asgerally T et al. (2005) Compartmental distinctions in uterine Muc-1 expression during early pregnancy in cynomolgous macaque (Macaca fascicularis) and baboon (Papio anubis). Hum Reprod 20:1493-503
Cameo, Paula; Srisuparp, Santha; Strakova, Zuzana et al. (2004) Chorionic gonadotropin and uterine dialogue in the primate. Reprod Biol Endocrinol 2:50
Nakayama, Jun; Aoki, Daisuke; Suga, Tomoaki et al. (2003) Implantation-dependent expression of trophinin by maternal fallopian tube epithelia during tubal pregnancies: possible role of human chorionic gonadotrophin on ectopic pregnancy. Am J Pathol 163:2211-9
Jaffe, R C; Donnelly, K M; Fazleabas, A T (2003) The induction of baboon glycodelin expression by progesterone is not through Sp1. Mol Hum Reprod 9:35-40
Srisuparp, Santha; Strakova, Zuzana; Brudney, Allison et al. (2003) Signal transduction pathways activated by chorionic gonadotropin in the primate endometrial epithelial cells. Biol Reprod 68:457-64
Kumar, Sushma; Brudney, Allison; Cheon, Yong-Pil et al. (2003) Progesterone induces calcitonin expression in the baboon endometrium within the window of uterine receptivity. Biol Reprod 68:1318-23
Srisuparp, S; Strakova, Z; Fazleabas, A T (2001) The role of chorionic gonadotropin (CG) in blastocyst implantation. Arch Med Res 32:627-34
Leach, R E; Khalifa, R; Armant, D R et al. (2001) Heparin-binding EGF-like growth factor modulation by antiprogestin and CG in the baboon (Papio anubis). J Clin Endocrinol Metab 86:4520-8

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