Indrani Bagchi
Professor, Veterinary Biosciences
Chair of the Physiology Division, Veterinary Bioscience
Professional Interests: Professional
Interests: Regulation of blastocyst implantation by estrogen
and progesterone receptors; identification of steroid receptor-regulated
genes by cDNA microarray; functional characterization of steroid-regulated
genes using knockout mouse models; mechanism of action of specific
estrogen and progesterone receptor modulators (SERMs and SPRMs).
Molecular Basis of Steroid Hormone Action in
the Female Reproductive Tract
The research in my laboratory is directed towards understanding the
molecular basis of steroid hormone action in the female reproductive
tract during embryonic implantation. Implantation of the embryo into
the wall of the uterus is a crucial event in mammalian embryogenesis.
The initiation of the complex interactions between the embryo and the
endometrium is determined by a timely interplay of the ovarian hormones,
estrogen and progesterone. These hormones induce pronounced changes
in cell proliferation and differentiation in the uterus and prepare
it to be "receptive" to
the invasion of the embryo. At the cellular level, estrogen and progesterone
act through their respective nuclear receptors, which function as modulators
of expression of specific gene networks. The central goal of my laboratory
is to isolate, identify, and functionally characterize the steroid-regulated
genes that are key to embryo implantation.
We have recently utilized the cDNA micro array analysis to identify estrogen-
and progesterone-regulated genes, which are potential regulators of uterine
function during implantation. We have identified several genes, which
are either up- or down-regulated by specific estrogen or progesterone
receptor modulators in rodent endometrium during implantation. A major
goal of my laboratory is to determine the patterns of spatio-temporal
expression and hormonal regulation of these putative implantation stage-specific
genes in the endometrium. We are also investigating the roles of certain
candidate genes during implantation by performing functional knock-outs
by targeted germ line mutagenesis. We have also developed in the laboratory
a methodology to specifically manipulate gene expression in the uterus
by employing antisense oligodeoxynucleotides (ODNs). Using this technique,
we have demonstrated that the peptide hormone calcitonin, which is induced
by progesterone in the uterus, plays a critical role at the time of implantation.
In this way, using a combination of various molecular, cellular, and
genetic approaches, we hope to gain insights into as yet unknown pathways
regulated by the steroid hormone, which control embryo-endometrial interactions.
Selected Publications:
Chen D, Xu X, Cheon YP, Bagchi MK, Bagchi IC . (2004) Estrogen induces expression of secretory leukocyte protease inhibitor in rat uterus. Biol Reprod , 71:508-514.
Li Q, Cheon YP, Kannan A, Sankar S, Bagchi IC and Bagchi MK. (2004) A novel pathway involving progesterone receptor, 12/15 lipoxigenase-derived eicosanoids, and peroxisome proliferator activatoed receptor gamma regulates implantation in mice. J Biol Chem. 279:11570-81.
Cheon YP, DeMayo FJ, Bagchi MK and Bagchi IC. (2004) Induction of Cytotoxic T-lymphocyte Antigen-2 Beta, a Cysteine Protease Inhibitor in Decidua: A Potential Regulator of Embryo Implantation. J Biol. Chem. 279:10357-63.
Cheon YP, Xu X, Bagchi MK and Bagchi IC. (2003) 3 Immune-Responsive Gene 1 (Irg1) is a novel target of progesterone receptor and plays a critical role during implantation in the mouse. Endocrinology. 144:5623-30.
Bagchi IC, Cheon YP, Li Q and Bagchi MK. (2003) Progesterone receptor-regulated gene networks in implantation. Frontiers in Bioscience. 8:852-61.
Kumar S, Brudney A, Cheon YP, Fazleabas AT and Bagchi IC. (2003) Progesterone Induces Calcitonin Expression in the Baboon Endometrium Within the Window of Uterine Receptivity. Biol Reprod. 68:1318-132.
Cheon YP, Li Q, DeMayo FJ, Bagchi IC and Bagchi MK. (2002) A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation. Mol Endocrinol. 16:2853-2871.
Li Q, Wang J, Armant DR, Bagchi MK and Bagchi IC. (2002) Calcitonin Down-Regulates E-cadherin Expression in Uterine Epithelium during Implantation. J Biol Chem. 277:46447-46455.
Bagchi, IC, Li, Q, and Cheon, Y. P. (2001) Role of steroid hormone-regulated genes in implantation. Ann. NY Acad Sci. 943:68-76.
Kumar S, Angervo M, Bagchi, MK, and Bagchi, IC. (2001) Isolation of steroid-regulated genes from the uterus by mRNA differential display. In: Steroid Receptor Methods: Protocols and Assays (B. A., Lieberman, ed.) The Humana Press Inc. pp: 105-117.
