Endocrinology, Vol 125, 1683-1690, Copyright © 1989 by Endocrine Society

ARTICLES

Cell type-specific localization of c-myc protein in the mouse uterus: modulation by steroid hormones and analysis of the periimplantation period

YM Huet-Hudson, GK Andrews and SK Dey
Department of Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.

Estrogen has been shown to induce a rapid transient increase in c-myc mRNA in the rat uterus. However, no studies of the cell specificity of c-myc expression in the uterus have been reported, and nothing is known about the expression of c-myc in response to other steroids or during normal uterine preparation for implantation. To this end, the cell type- specific localization of c-myc protein was determined in the ovariectomized mouse uterus after progesterone (P4) and/or 17 beta- estradiol (E2) injection as well as during the periimplantation period. After E2 injection, a rapid accumulation of c-myc protein was detected exclusively in the uterine luminal and glandular epithelial nuclei in the ovariectomized mouse. Essentially all of these cells contained immunoreactive c-myc by 12 h postinjection. In contrast, after P4 injection, rapid accumulation of c-myc was noted exclusively in some of the stromal cell nuclei. Pretreatment of the ovariectomized mouse for 4 days with P4 (P4 priming) followed by E2 injection resulted in an increase in the number of c-myc-positive stromal cells, but few, if any, c-myc-positive cells were detected in the luminal and glandular epithelia. These uterine cell type-specific localizations of c-myc protein, induced by E2 or P4 injection, were followed within 18-24 h by DNA synthesis ([ 3H]thymidine incorporation) restricted to the epithelia or stroma, respectively. c-Myc was detected in the nuclei of luminal and glandular epithelia during proestrus and on days 1 and 2 of pregnancy, a period when the uterus is under the influence of estrogen. c-Myc-positive cells were detected in the stroma on day 3, and by day 4 a large number of stromal cell nuclei were c-myc positive. These changes are coincident with increasing P4 levels during early pregnancy. At the implantation chamber on day 5, many cells in the primary decidual zone as well as some of the deeper stromal cells were c-myc protein positive, whereas on day 6, c-myc protein was detected only in the secondary decidual zone. During this period of uterine preparation for embryo implantation and subsequent decidualization, there was a positive correlation between c-myc protein localized in specific populations of uterine cells and subsequent DNA synthesis in those cell types. Thus, both E2 and P4 induce cell type-specific accumulation of c-myc protein in the uterus of the ovariectomized mouse, with E2 induction of c-myc being restricted to epithelia, and P4 induction restricted to stroma.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				A.A Fouladi-Nashta, L Mohamet, J.K Heath, and S.J Kimber Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif-/- Mouse Uterus Biol Reprod, July 1, 2008; 79(1): 142 - 153. [Abstract] [Full Text] [PDF]

				Z. Lu, J. Hardt, and J.J. Kim Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation Mol. Hum. Reprod., June 1, 2008; 14(6): 357 - 366. [Abstract] [Full Text] [PDF]

				S. Ray, F. Xu, H. Wang, and S. K. Das Cooperative Control via Lymphoid Enhancer Factor 1/T Cell Factor 3 and Estrogen Receptor-{alpha} for Uterine Gene Regulation by Estrogen Mol. Endocrinol., May 1, 2008; 22(5): 1125 - 1140. [Abstract] [Full Text] [PDF]

				J.-W. Jeong, K. Y. Lee, S. J. Han, B. J. Aronow, J. P. Lydon, B. W. O'Malley, and F. J. DeMayo The p160 Steroid Receptor Coactivator 2, SRC-2, Regulates Murine Endometrial Function and Regulates Progesterone-Independent and -Dependent Gene Expression Endocrinology, September 1, 2007; 148(9): 4238 - 4250. [Abstract] [Full Text] [PDF]

				H. Song, K. Han, and H. Lim Progesterone supplementation extends uterine receptivity for blastocyst implantation in mice Reproduction, February 1, 2007; 133(2): 487 - 493. [Abstract] [Full Text] [PDF]

				J-W Jeong, K Y Lee, J P Lydon, and F J DeMayo Steroid hormone regulation of Clca3 expression in the murine uterus. J. Endocrinol., June 1, 2006; 189(3): 473 - 484. [Abstract] [Full Text] [PDF]

				Q. Zhang and B. C. Paria Importance of Uterine Cell Death, Renewal, and Their Hormonal Regulation in Hamsters that Show Progesterone-Dependent Implantation Endocrinology, May 1, 2006; 147(5): 2215 - 2227. [Abstract] [Full Text] [PDF]

				T. Daikoku, S. Tranguch, D. B. Friedman, S. K. Das, D. F. Smith, and S. K. Dey Proteomic Analysis Identifies Immunophilin FK506 Binding Protein 4 (FKBP52) as a Downstream Target of Hoxa10 in the Periimplantation Mouse Uterus Mol. Endocrinol., March 1, 2005; 19(3): 683 - 697. [Abstract] [Full Text] [PDF]

				K. Y Lee and F. J DeMayo Animal models of implantation Reproduction, December 1, 2004; 128(6): 679 - 695. [Abstract] [Full Text] [PDF]

				N. Brown, K. Deb, B. C. Paria, S. K. Das, and J. Reese Embryo-Uterine Interactions via the Neuregulin Family of Growth Factors During Implantation in the Mouse Biol Reprod, December 1, 2004; 71(6): 2003 - 2011. [Abstract] [Full Text] [PDF]

				S. K. Dey, H. Lim, S. K. Das, J. Reese, B. C. Paria, T. Daikoku, and H. Wang Molecular Cues to Implantation Endocr. Rev., June 1, 2004; 25(3): 341 - 373. [Abstract] [Full Text] [PDF]

				N. Baran, P. A. Kelly, and N. Binart Decysin, a New Member of the Metalloproteinase Family, Is Regulated by Prolactin and Steroids During Mouse Pregnancy Biol Reprod, May 1, 2003; 68(5): 1787 - 1792. [Abstract] [Full Text] [PDF]

				W.-g. Ma, H. Song, S. K. Das, B. C. Paria, and S. K. Dey Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation PNAS, March 4, 2003; 100(5): 2963 - 2968. [Abstract] [Full Text] [PDF]

				T. Daikoku, H. Matsumoto, R. A. Gupta, S. K. Das, M. Gassmann, R. N. DuBois, and S. K. Dey Expression of Hypoxia-inducible Factors in the Peri-implantation Mouse Uterus Is Regulated in a Cell-specific and Ovarian Steroid Hormone-dependent Manner. EVIDENCE FOR DIFFERENTIAL FUNCTION OF HIFs DURING EARLY PREGNANCY J. Biol. Chem., February 21, 2003; 278(9): 7683 - 7691. [Abstract] [Full Text] [PDF]

				Y.-P. Cheon, Q. Li, X. Xu, F. J. DeMayo, I. C. Bagchi, and M. K. Bagchi A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation Mol. Endocrinol., December 1, 2002; 16(12): 2853 - 2871. [Abstract] [Full Text] [PDF]

				N. Baran, P. A. Kelly, and N. Binart Characterization of a Prolactin-Regulated Gene in Reproductive Tissues Usingthe Prolactin Receptor Knockout Mouse Model Biol Reprod, April 1, 2002; 66(4): 1210 - 1218. [Abstract] [Full Text] [PDF]

				H. Song, H. Lim, S. K. Das, B. C. Paria, and S. K. Dey Dysregulation of EGF Family of Growth Factors and COX-2 in the Uterus during the Preattachment and Attachment Reactions of the Blastocyst with the Luminal Epithelium Correlates with Implantation Failure in LIF- Deficient Mice Mol. Endocrinol., August 1, 2000; 14(8): 1147 - 1161. [Abstract] [Full Text]

				N. Idris and K. L. Carraway Sialomucin Complex (Muc4) Expression in the Rat Female Reproductive Tract Biol Reprod, December 1, 1999; 61(6): 1431 - 1438. [Abstract] [Full Text]

				J. Tan, B. C. Paria, S. K. Dey, and S. K. Das Differential Uterine Expression of Estrogen and Progesterone Receptors Correlates with Uterine Preparation for Implantation and Decidualization in the Mouse Endocrinology, November 1, 1999; 140(11): 5310 - 5321. [Abstract] [Full Text]

				H. Lim, L. Ma, W.-g. Ma, R. L. Maas, and S. K. Dey Hoxa-10 Regulates Uterine Stromal Cell Responsiveness to Progesterone during Implantation and Decidualization in the Mouse Mol. Endocrinol., June 1, 1999; 13(6): 1005 - 1017. [Abstract] [Full Text]

				B. C. Paria, J. Tan, D. B. Lubahn, S. K. Dey, and S. K. Das Uterine Decidual Response Occurs in Estrogen Receptor-{alpha}-Deficient Mice Endocrinology, June 1, 1999; 140(6): 2704 - 2710. [Abstract] [Full Text]

				B.C. Paria, X. Zhao, J. Wang, S.K. Das, and S.K. Dey Fatty-Acid Amide Hydrolase Is Expressed in the Mouse Uterus and Embryo during the Periimplantation Period Biol Reprod, May 1, 1999; 60(5): 1151 - 1157. [Abstract] [Full Text]

				B. C. Paria, H. Lim, X.-N. Wang, J. Liehr, S. K. Das, and S. K. Dey Coordination of Differential Effects of Primary Estrogen and Catecholestrogen on Two Distinct Targets Mediates Embryo Implantation in the Mouse Endocrinology, December 1, 1998; 139(12): 5235 - 5246. [Abstract] [Full Text] [PDF]

				B. C. Paria, N. Das, S. K. Das, X. Zhao, K. N. Dileepan, and S. K. Dey Histidine Decarboxylase Gene in the Mouse Uterus Is Regulated by Progesterone and Correlates with Uterine Differentiation for Blastocyst Implantation Endocrinology, September 1, 1998; 139(9): 3958 - 3966. [Abstract] [Full Text] [PDF]

				P. Bilinski, D. Roopenian, and A. Gossler Maternal IL-11Ralpha function is required for normal decidua and fetoplacental development in mice Genes & Dev., July 15, 1998; 12(14): 2234 - 2243. [Abstract] [Full Text]

				R. E. Meskini, C. Delfino, F. Boudouresque, C. Oliver, P.-M. Martin, and L'H. Ouafik Evidence of high expression of peptidylglycine alpha -amidating monooxygenase in the rat uterus: Estrogen regulation PNAS, June 9, 1998; 95(12): 7191 - 7196. [Abstract] [Full Text] [PDF]

				P. C. Schmid, B. C. Paria, R. J. Krebsbach, H. H. O. Schmid, and S. K. Dey Changes in anandamide levels in mouse uterus are associated with uterine receptivity for embryo implantation PNAS, April 15, 1997; 94(8): 4188 - 4192. [Abstract] [Full Text] [PDF]

				H. Lim, S. K. Dey, and S. K. Das Differential Expression of the erbB2 Gene in the Periimplantation Mouse Uterus: Potential Mediator of Signaling by Epidermal Growth Factor-Like Growth Factors Endocrinology, March 1, 1997; 138(3): 1328 - 1337. [Abstract] [Full Text] [PDF]

				G. Benson, H Lim, B. Paria, I Satokata, S. Dey, and R. Maas Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression Development, January 9, 1996; 122(9): 2687 - 2696. [Abstract] [PDF]

				S. Das, X. Wang, B. Paria, D Damm, J. Abraham, M Klagsbrun, G. Andrews, and S. Dey Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation Development, January 5, 1994; 120(5): 1071 - 1083. [Abstract] [PDF]

				V. Braga and S. Gendler Modulation of Muc-1 mucin expression in the mouse uterus during the estrus cycle, early pregnancy and placentation J. Cell Sci., January 6, 1993; 105(2): 397 - 405. [Abstract] [PDF]