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Endocrinology Vol. 140, No. 6 2672-2678
Copyright © 1999 by The Endocrine Society

ARTICLES

Expression of Cyclooxygenase-1 and -2 in the Baboon Endometrium during the Menstrual Cycle and Pregnancy1

J. Julie Kim2, J. Wang2, C. Bambra, S. K. Das, S. K. Dey and A. T. Fazleabas

Department of Obstetrics and Gynecology, University of Illinois (J.J.K., A.T.F.), Chicago, Illinois 60612; the Departments of Molecular and Integrative Physiology (J.W., S.K.Da., S.K.De.) and Obstetrics and Gynecology (S.K.Da.), University of Kansas Medical Center, Kansas City, Kansas 66160; and Institute for Primate Research (C.B.), Nairobi, Kenya

Address all correspondence and requests for reprints to: Dr. A. T. Fazleabas, Department of Obstetrics and Gynecology, University of Illinois, 820 S Wood Street, M/C 808, Chicago, Illinois 60612. E-mail: asgi{at}uic.edu


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Cyclooxygenase (COX) is the rate-limiting enzyme in the biosynthesis of PGs. PGs together with ovarian steroids play important regulatory roles in the establishment and maintenance of pregnancy in a number of different species. In the primate, little is known about the role of PGs in these processes. In this study, the uterine expression of COX-1 and COX-2 throughout the menstrual cycle [late follicular, day 5 postovulation (PO), day 10 PO, and day 14 PO] and pregnancy (days 12–18, day 39, day 51, and near term) was analyzed using semiquantitative RT-PCR, in situ hybridization, and immunocytochemistry. During the menstrual cycle, the highest expression of COX-1 occurred in luteal phase endometrium and was localized to the surface and glandular epithelium. The stromal cells did not express detectable levels of COX-1 at any time. COX-2 messenger RNA (mRNA) expression, as measured by RT-PCR, was evident at all stages of the menstrual cycle, and in situ hybridization showed specific localization for this mRNA in the epithelial cells during the cycle. Treatment of animals with the antiprogestin (ZK 137.316) for 9 days (beginning on the day of the LH surge) inhibited COX-1 expression in the epithelium when the tissue was analyzed on day 10 PO, whereas COX-2 expression disappeared in the epithelium and increased in the stroma. With the onset of pregnancy, COX-1 expression in epithelial cells decreased dramatically. In contrast, COX-2 continued to be detected on the surface epithelium and was also strongly expressed specifically in the stromal cells at the site of implantation. Immunocytochemical staining for COX-2 showed the same pattern of expression for the protein as the message. Finally, near-term decidua expressed very little COX-1 or COX-2 mRNA. These studies suggest that in the baboon endometrium, COX-1 expression is regulated primarily by progesterone, whereas regulation of COX-2 expression may involve additional mediators of embryonic origin at the site of implantation.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
CYCLOOXYGENASE (COX) is the rate-limiting enzyme that catalyzes the initial step in the formation of PGs from arachidonic acid (1). COX is encoded by two separate genes, COX-1 and COX-2, both of which catalyze the formation of a variety of eicosanoids that include PGD2, PGE2, PGI2, PGF2{alpha}, and thromboxane A. The type of PGs produced varies depending on the downstream enzymatic machinery present in a particular cell type (2). Although COX-1 is expressed constitutively in a wide range of tissues, COX-2 is inducible by tumor promoters, growth factors, and cytokines. The COX enzymes have been extensively studied in different cell types, tissues, and species, and it is now thought that eicosanoids produced by COX-1 are important for the housekeeping functions, whereas those produced by COX-2 lead to various pathological changes in body tissues (2, 3).

The endometrium undergoes striking morphological changes during the menstrual cycle and pregnancy. Under the influence of hormones and the developing embryo, changes in the local synthesis and metabolism of a variety of bioactive substances occur. Among these are PGs, which are potent biological mediators that act locally. They are considered to be proinflammatory and have been implicated in such mechanisms as ovulation (4, 5), menstruation (6), implantation (7, 8), and decidualization (8, 9, 10). The endometrium produces varying levels of PGs during the menstrual cycle and in pregnancy. In women, endometrial PG production is higher in the luteal phase and during menstruation than in the follicular phase (6, 11). In the rodent, PGs are implicated as important mediators of endometrial vascular permeability, which is evident at the site of implantation (9, 12). In ruminants, PGs of uterine origin are actively involved in luteolysis (13).

It is apparent that PGs are important mediators for the establishment of successful pregnancy in different species. Despite the extensive studies reported on COX expression, regulation, and potential function in the reproductive processes of other species, relatively little is known about COX expression and regulation in the primate uterus. Our laboratory focuses on delineating the events involved with maternal recognition of pregnancy, implantation, and establishment of pregnancy in the primate. In this report, we demonstrate the in vivo expression and localization of COX-1 and COX-2 in the baboon (Papio anubis) endometrium throughout the menstrual cycle and pregnancy.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals
Endometrial tissues (n = 2–4 from each group) were obtained from cycling [late follicular, day 5 postovulation (PO), day 10 PO, and day 14 PO], pregnant (days 12–18, day 39, day 51, and near term), and antiprogestin-treated (day 10 PO) baboons (Papio anubis). The day of ovulation was designated as 2 days after the estradiol surge and was confirmed by prospective measurement of peripheral serum levels of estradiol (14). For antiprogestin treatment, normally cycling animals received the antiprogestin ZK 137.316 (Schering AG, Berlin, Germany) at 1 mg/kg BW·day for 9 days beginning on the day of the LH surge. This regimen inhibits the down-regulation of the progesterone receptor in both the lumenal and glandular epithelium on day 10 PO (15).

RT-PCR
Tissue was homogenized in TriReagent (Molecular Research Center, Inc., Cincinnati, OH), and RNA was extracted using the protocol provided by the manufacturer. Aliquots of total RNA isolated from baboon tissues were treated with 1 U/µl deoxyribonuclease (Promega Corp., Madison, WI). RT was then performed in a final volume of 20 µl with 1 µg RNA and 50 U/µl murine leukemia virus reverse transcriptase at 42 C for 30 min. PCR amplification was performed with the RT product, the appropriate primers (50 pmol/tube), 0.5 µl 5 U/ml Taq polymerase (Life Technologies, Grand Island, NY), and 0.25 µl 10 mCi/ml [{alpha}-32P]deoxy-CTP. After an initial incubation at 94 C for 10 min, 32 amplification cycles consisting of 94 C (1 min), 55 C (1 min), and 72 C (2 min) were performed followed by 15 min of final extension at 72 C. A linear curve was plotted using the number of cycles of amplification vs. the densitometric values of the PCR products, measured with a PhosphorImager (Molecular Dynamics, Inc., Sunnyvale, CA). The optimal number of cycles for amplification that fit within the linear range was chosen for each set of primers. Primers for COX-1 (sense, TCC AAC CTT ATC CCC AGT C; antisense, CAT GGC AAT GCG GTT GC) or COX-2 (sense, TCC AGA TCA CAT TTG ATT GAC A; antisense, TCT TTG ACT GTG GGA GGA TAC A) and H3.3 (described in Ref. 16) were added together in a single tube so that amplification of the complementary DNAs for H3.3 and COX-1 or COX-2 occurred in the same tube. The PCR products were electrophoresed in 1.5% agarose gels, and the gels were dried and exposed to film. Densitometric analysis of the PCR products was performed using a PhosphorImager system. The densitometric values were normalized to H3.3, which was coamplified as an internal standard (16). The specificities of the PCR products for COX-1 and COX-2 were verified by Southern hybridization. A specific oligonucleotide sequence within the gene product derived from PCR was end labeled with [{gamma}-32P]ATP. The unlabeled COX-1 and COX-2 PCR products were electrophoresed on a 1.5% agarose gel and hybridized with the [{gamma}-32P]ATP-labeled internal oligonucleotide. The authenticity of the PCR products was verified after exposure to film at -80 C.

Immunocytochemistry
Immunolocalization of COX-2 was performed in Bouin’s fixed paraffin-embedded sections using a Zymed-Histostain-SP kit (Zymed Laboratories, Inc., San Francisco, CA) (7, 8). The polyclonal antipeptide COX-2 antibody (corresponding to amino acids 563–577) was generated against the highly conserved C-terminal region of this molecule (7, 8). The antibody was used at a concentration of 5 µg/ml. Mouse implantation sites (day 5) were used as positive controls, and negative controls consisted of preimmune serum at the same concentration as the immune serum.

In situ hybridization
In situ hybridization was performed as described in Das et al. (17). Frozen sections of tissue were mounted onto poly-L-lysine-coated slides and stored at -70 C until used. After removal from -70 C, the slides with the uterine sections were placed on a slide warmer (37 C) for 2 min and then fixed in 4% paraformaldehyde in PBS for 15 min at 4 C. After prehybridization, uterine sections were hybridized to 35S-labeled sense or antisense complementary RNA probes specific for mouse COX-1 and human COX-2 for 4 h at 45 C. After hybridization and washing, the slides were incubated with ribonuclease A (20 µg/ml) at 37 C for 15 min. Ribonuclease A-resistant hybrids were detected after 1–3 weeks of autoradiography using Kodak NTB-2 liquid emulsion (Eastman Kodak Co., Rochester, NY). The slides were poststained with hematoxylin and eosin.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Expression of COX-1 and COX-2 messenger RNA (mRNA) in endometrial tissue
The expression of COX-1 and COX-2 mRNA in endometrial tissue from various stages of the menstrual cycle and pregnancy was measured by RT-PCR (Fig. 1Go). Although COX-1 was faintly detectable in the late follicular phase tissue (Fig. 1AGo, lane 1), its expression increased during the luteal phase of the menstrual cycle (Fig. 1AGo, lanes 2–4). After the establishment of pregnancy, the signal for COX-1 was relatively weak compared with that of the luteal phase tissues (Fig. 1AGo, lanes 5–8). The corresponding histogram, which shows the mean densitometric values from two animals normalized to the internal standard H3.3, also demonstrated a similar pattern of expression. COX-2 mRNA expression in endometrial tissues, as determined by RT-PCR, appeared to be uniform throughout the menstrual cycle and early pregnancy (Fig. 1BGo). However, in near-term decidua, COX-2 expression was much lower compared with that in endometrial tissues at other stages of the cycle and pregnancy. The densitometric analysis from two animals shown in the corresponding histogram demonstrated a similar pattern of expression.



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  		Figure 1. COX-1 and -2 expression in endometrial tissue from cycling and pregnant baboons. Total RNA from tissues from different stages of the menstrual cycle (lane 1, late follicular; lane 2, day 5 PO; lane 3, day 10 PO; lane 4, day 14 PO) and pregnancy (lane 5, days 12–13; lane 6, day 32; lane 7, day 52; lane 8, day 177 decidua) was isolated and subjected to RT-PCR. COX-1 (A) and COX-2 (B) are shown with the corresponding histograms of densitometric analysis expressed as the mean of two replicate determinations.

 
Expression of COX-1 and COX-2 in the endometrium was dramatically modulated in animals that were treated with antiprogestin. Whereas COX-1 expression was high in the day 10 postovulatory animals (Fig. 2AGo, lane 1), litle or no COX-1 was detected in the endometrium of antiprogestin-treated animals (Fig. 2AGo, lane 2). Alternatively, COX-2 was expressed in the endometrium of both the control (day 10 PO; Fig. 2BGo, lane 1) and the antiprogestin-treated animals (Fig. 2BGo, lane 2).



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  		Figure 2. Effect of antiprogestin treatment on COX-1 and -2 expression in baboon endometrium. Normally cycling animals received the antiprogestin ZK 137.316 for 9 days beginning on the day of the LH surge. Total RNA from the endometrium was isolated and subjected to RT-PCR. COX-1 (A) and COX-2 (B) are shown for normal cycling day 10 PO endometrium (lane 1) and for an antiprogestin-treated animal (lane 2), with the corresponding densitometric analysis expressed as the mean of two replicate determinations.

 
Localization of COX-1 and COX-2 mRNA in the baboon endometrium
COX-1 and COX-2 mRNA expression in the endometrium was visualized by in situ hybridization. No positive hybridization was observed for COX-1 in the late follicular phase tissue (data not shown). Day 5 PO tissues exhibited strong signals for COX-1 in both the lumenal and glandular epithelium (Fig. 3Go, A and B). The stromal cells were negative for COX-1. COX-2 was also expressed in the lumenal epithelium of day 5 PO tissue (Fig. 3CGo), but the signals in the glands were less intense and not as dramatic as those of COX-1 (Fig. 3DGo). Stromal cells were also negative for COX-2. No hybridization signals were evident when sense probes were used for either COX-1 or COX-2.



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  		Figure 3. In situ hybridization of COX-1 mRNA in the lumenal epithelium (A) and glands (B) and of COX2 mRNA in the lumenal epithelium (C) and glands (D) on day 5 PO. Note the limited expression of COX-2 in the glandular epithelium compared with COX-1. Magnification, x160.

 
Endometrial tissues from animals treated with antiprogestin during the luteal phase demonstrated that both the lumenal and glandular epithelia were negative for COX-1 (Fig. 4BGo) compared with the normally cycling day 10 PO controls (Fig. 4AGo). COX-2 hybridization was localized to the stromal cells in the endometrium of antiprogestin-treated animals, whereas the lumenal and glandular epithelia were negative (Fig. 4DGo). Endometrium from control animals on day 10 PO also exhibited hybridization for COX-2 primarily in the lumenal epithelium, but not in the glandular epithelium (Fig. 3Go, C and D, and Fig. 4CGo).



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  		Figure 4. In situ hybridization of COX-1 and -2 mRNA in the baboon endometrium after treatment with the antiprogestin. Note the intense hybridization of COX-1 in the endometrium of the control animals on day 10 PO (A) compared with that in antiprogestin-treated baboons at the same time point (B). COX-2 expression in the glandular endometrium in control animals on day 10 PO was minimal (C; compare with Fig. 3DGo). Treatment with the antiprogestin resulted in an increase in hybridization in stromal cells (D). Magnification, x100.

 
Endometrial tissues from pregnant animals were divided into implantation and nonimplantation sites. COX-1 mRNA expression in the epithelium decreased dramatically in early pregnant endometrial tissues (days 17–19 pregnancy; Fig. 5AGo). Very faint expression was observed in some of the glands. COX-2 expression again differed from COX-1 expression in early pregnant tissues. At the nonimplantation site, a positive signal for COX-2 mRNA was observed in lumenal epithelium (Fig. 5BGo), whereas glandular epithelium remained negative. COX-1 mRNA expression was absent at the implantation site (Fig. 5CGo), whereas COX-2 mRNA expression was intense and localized specifically in the decidualizing cells of the maternal tissue (Fig. 5DGo). Other regions were negative for COX-2 mRNA. The pattern of immunostaining for COX-2 protein was identical to that of the mRNA. Lumenal epithelium stained positively for COX-2 protein at the nonimplantation site (Fig. 6BGo), whereas decidualizing cells in maternal tissue at the implantation site stained positively for COX-2 protein (Fig. 6AGo). Near-term decidua displayed no hybridization for either COX-1 or COX-2 mRNA (data not shown).



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  		Figure 5. In situ hybridization of COX-1 and COX-2 mRNA in day 17–19 pregnant endometrium. Hybridization of COX-1 in the lumenal epithelium and neck glands at the nonimplantation site was minimal (A), whereas COX-2 expression in the lumenal epithelium remained strong (B). At the implantation site, hybridization of COX-1 (C) was undetectable, whereas strong hybridization for COX-2 was evident in the decidualizing stromal cells (D). Magnification, x160. CTS, Cytotrophoblastic shell; Endo, endometrium.

 


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  		Figure 6. Immunocytochemical localization of COX-2 protein in day 17–19 pregnant endometrium. COX-2 protein localization corresponds to the in situ hybridization data. Decidualizing stromal cells (Dc; arrowed) stain positively at the site of implantation (A). At the nonimplantation site, the majority of the staining is limited to the lumenal epithelium (LE). The inset in B is a preimmune control. Magnification, x40.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This report demonstrates the unique patterns of expression of COX-1 and COX-2 in the baboon endometrium throughout the menstrual cycle and pregnancy. Follicular stage endometrium did not express COX-1, whereas COX-2 mRNA was detected by RT-PCR. Luteal phase tissues expressed high levels of COX-1, specifically in the lumenal and glandular epithelium, whereas COX-2 expression was limited to lumenal epithelium, with some expression in glands. Antiprogestin treatment dramatically reduced COX-1 expression in the epithelium, whereas it induced COX-2 expression in the stromal cells. Finally, COX-1 expression decreased with pregnancy, with only traces of hybridization in some of the neck glands. Alternatively, COX-2 mRNA expression was intense at the implantation site, specifically in the decidualizing stromal cells. Near the end of pregnancy, neither COX-1 nor COX-2 was detectable in the decidua.

COX has been detected in the endometrium of different species even before the identification of COX-2 as a unique gene product. In the human endometrium, strong positive staining for COX was observed on the surface epithelium, with rather weak immunoreactivity on the glands and no staining on the stromal cells (18). Rees et al. (19) demonstrated staining of COX in surface and glandular epithelium, specifically in luteal phase human endometrium. No staining was observed at any time in the cycle in the endometrial stroma or in first trimester pregnant tissues or decidua. Finally, Shaw et al. (20) demonstrated much greater COX-1 gene expression in the endometrium than in the decidua. In this study, we have shown similar expression patterns for COX-1 in the baboon endometrium and demonstrated that the localization was restricted to epithelial cells and was most prominent in luteal phase tissues. Furthermore, COX expression was higher in endometrium than in near-term decidua.

It is generally believed that COX-1 is ubiquitously expressed whereas COX-2 is induced by mitogens and cytokines. However, it is evident from this study and others that COX-1 is also specifically regulated in the uterus. Bany et al. (21) demonstrated an increase in both COX-1 and COX-2 expression in response to epidermal growth factor in rat endometrial stromal cells. Vascular endothelial growth factor induces COX-1, but not COX-2, expression in both human and bovine endothelial cells (22). In the periimplantation mouse uterus, the COX-1 gene was expressed in the uterine epithelium during the preimplantation period until the initiation of attachment, after which time the expression was down-regulated (7). In our study, COX-1 expression in epithelial cells of the endometrium was up-regulated during the luteal phase and was down-regulated with the establishment of pregnancy. Moreover, the absence of COX-1 expression in antiprogestin-treated animals observed in this study strongly implicates a role for progesterone in its induction. These data are consistent with observations in the mouse uterus (7). Treatment with antiprogestins during the luteal phase prevents the down-regulation of the progesterone receptor and inhibits the normal differentiation process in the baboon endometrium during the secretory phase (15, 23). Thus, it is conceivable that the inhibition of progesterone action with the antiprogestin at the time of ovulation prevents the expected induction of COX-1 during the luteal phase. The loss of COX-1 expression during pregnancy may also be associated with the total down-regulation of the progesterone receptor in all uterine epithelial cells (24).

Although COX-1 homozygous mutant female mice demonstrated apparently normal reproductive and developmental events with some defects in parturition (8, 25), COX-2-deficient mice demonstrated defects in ovulation, fertilization, implantation, and decidualization (8). In the mouse, the COX-2 gene is expressed in the lumenal epithelium and subepithelial stromal cells at the time of the blastocyst attachment reaction (7). Treatment of ovariectomized mice with progesterone and/or estradiol failed to induce uterine COX-2 mRNA, suggesting that perhaps this gene is not inducible by ovarian steroids in the mouse uterus. We have also observed the distinct expression of COX-2 specifically at the implantation site in the baboon, primarily in the decidualizing stromal cells of the endometrium. The increased expression of COX-2 may be due to the presence and/or secretion of cytokines by the uterus and the implanting embryo (26). Interleukins, produced by both the endometrium and the embryo (26), are well known inducers of COX-2. CG, which is expressed in large quantities by the embryo, has been shown to up-regulate COX-2 gene expression in human endometrial stromal cells (27). Although the factors and events associated with COX-2 expression at the implantation site remain unclear, it is apparent that the embryo is what triggers the cascade of events leading to the expression of this enzyme specifically in decidual cells at the site of implantation.

It has been suggested that the distinct roles that COX-1 and -2 play in reproductive processes are due to differential subcellular sites of PG production induced by these enzymes. Although COX-1 and -2 are both membrane bound, COX-1 is present primarily in the endoplasmic reticulum, and COX-2 is present in both the endoplasmic reticulum and the perinuclear envelope (28). Lim et al. (8) demonstrated distinct perinuclear localization of COX-2 in endometrial cells exclusively surrounding the implanting blastocysts. It has been shown that eicosanoids can mediate transcription by activating the nuclear hormone receptor peroxisome proliferator-activated receptors (i.e. PPAR{alpha}, PPAR{gamma}, and PPAR{delta}) (29, 30). Thus, PGs synthesized by COX-2 localized on the nuclear membrane can subsequently act on nuclear receptors and regulate the transcription of essential genes.

In summary, the differences in COX-1 and COX-2 expression in specific cell types during the menstrual cycle and pregnancy suggest an important role for these enzymes in the primate uterus. Although COX-1 induction in epithelial cells is most likely influenced by the action of progesterone, COX-2 induction in surface epithelium and decidualizing stromal cells at the implantation site may involve factors other than ovarian steroids, such as cytokines and other proinflammatory mediators. The dilation of microvessels and increased capillary permeability observed during the luteal phase at the time of endometrial receptivity may involve PGs produced via COX-1 (31). COX-2, on the other hand, may be important in promoting decidualization of stromal cells during pregnancy.


   Acknowledgments
 
We thank Dr. David DeWitt of Michigan State University for kindly providing the human COX-2 complementary DNA.


   Footnotes
 
1 This work was supported by NIH Grant HD-29964, TW-00878 (to A.T.F.), HD-29968, HD-12304 (to S.K.D.), ES-07814 (to S.K.D.), and a postdoctoral fellowship from the Ernst Schering Research Foundation (Berlin, Germany; to J.J.K.). This work was performed as part of the National Cooperative Program for Markers of Uterine Receptivity for Blastocyst Implantation and was supported by Cooperative Agreement NIH-NICHHD 29964 (to A.T.F.) and HD-29968 (to S.K.D.). Back

2 These authors contributed equally to this work. Back

Received August 13, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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I. Ihnatovych, W. Hu, J. L. Martin, A. T. Fazleabas, P. de Lanerolle, and Z. Strakova
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Z. Strakova, P. Mavrogianis, X. Meng, J. M. Hastings, K. S. Jackson, P. Cameo, A. Brudney, O. Knight, and A. T. Fazleabas
In Vivo Infusion of Interleukin-1{beta} and Chorionic Gonadotropin Induces Endometrial Changes that Mimic Early Pregnancy Events in the Baboon
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D.X. Lin, Z.M. Lei, and Ch.V. Rao
Dependence of Uterine Cyclooxygenase2 Expression on Luteinizing Hormone Signaling
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C. Hermenegildo, P.J. Oviedo, M.C. Garcia-Martinez, M.A. Garcia-Perez, J.J. Tarin, and A. Cano
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K. Chwalisz, M. C. Perez, D. DeManno, C. Winkel, G. Schubert, and W. Elger
Selective Progesterone Receptor Modulator Development and Use in the Treatment of Leiomyomata and Endometriosis
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S. K. Dey, H. Lim, S. K. Das, J. Reese, B. C. Paria, T. Daikoku, and H. Wang
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T. Sun, S.-J. Li, H.-L. Diao, C.-B. Teng, H.-B. Wang, and Z.-M. Yang
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V. Emond, L. A. MacLaren, S. Kimmins, J. A. Arosh, M. A. Fortier, and R. D. Lambert
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Biol Reprod, January 1, 2004; 70(1): 54 - 64.
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Z. Strakova, M. Szmidt, S. Srisuparp, and A. T. Fazleabas
Inhibition of Matrix Metalloproteinases Prevents the Synthesis of Insulin-Like Growth Factor Binding Protein-1 during Decidualization in the Baboon
Endocrinology, December 1, 2003; 144(12): 5339 - 5346.
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K. Tsuboi, A. Iwane, S. Nakazawa, Y. Sugimoto, and A. Ichikawa
Role of Prostaglandin H2 Synthase 2 in Murine Parturition: Study on Ovariectomy-Induced Parturition in Prostaglandin F Receptor-Deficient Mice
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O. Yoshino, Y. Osuga, Y. Hirota, K. Koga, T. Hirata, T. Yano, T. Ayabe, O. Tsutsumi, and Y. Taketani
Endometrial Stromal Cells Undergoing Decidualization Down-Regulate Their Properties to Produce Proinflammatory Cytokines in Response to Interleukin-1{beta} via Reduced p38 Mitogen-Activated Protein Kinase Phosphorylation
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S. Kumar, A. Brudney, Y.-P. Cheon, A. T. Fazleabas, and I. C. Bagchi
Progesterone Induces Calcitonin Expression in the Baboon Endometrium Within the Window of Uterine Receptivity
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S. Srisuparp, Z. Strakova, A. Brudney, S. Mukherjee, S. Reierstad, M. Hunzicker-Dunn, and A. T. Fazleabas
Signal Transduction Pathways Activated by Chorionic Gonadotropin in the Primate Endometrial Epithelial Cells
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H. L. Rupnow, T. M. Phernetton, M. L. Modrick, M. C. Wiltbank, I. M. Bird, and R. R. Magness
Endothelial Vasodilator Production by Uterine and Systemic Arteries. VIII. Estrogen and Progesterone Effects on cPLA2, COX-1, and PGIS Protein Expression
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C.J.P. Jones and A.T. Fazleabas
Ultrastructure of epithelial plaque formation and stromal cell transformation by post-ovulatory chorionic gonadotrophin treatment in the baboon (Papio anubis)
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Y. Ohata, T. Harada, A. Fujii, S. Yoshida, T. Iwabe, and N. Terakawa
Menstrual cycle-specific inhibition of endometrial stromal cell proliferation by oncostatin M
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T. Sato, H. Michizu, K. Hashizume, and A. Ito
Hormonal regulation of PGE2 and COX-2 production in rabbit uterine cervical fibroblasts
J Appl Physiol, April 1, 2001; 90(4): 1227 - 1231.
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Z. Strakova, S. Srisuparp, and A. T. Fazleabas
Interleukin-1{beta} Induces the Expression of Insulin-Like Growth Factor Binding Protein-1 during Decidualization in the Primate
Endocrinology, December 1, 2000; 141(12): 4664 - 4670.
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M. Pall, M. Mikuni, K. Mitsube, and M. Brännström
Time-Dependent Ovulation Inhibition of a Selective Progesterone-Receptor Antagonist (Org 31710) and Effects on Ovulatory Mediators in the In Vitro Perfused Rat Ovary
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H. Lim, R. A. Gupta, W.-g. Ma, B. C. Paria, D. E. Moller, J. D. Morrow, R. N. DuBois, J. M. Trzaskos, and S. K. Dey
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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
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