| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Department of Molecular and Integrative Physiology (B.C.P., N.D., S.K.Da., X.Z., S.K.De.) and Medicine (K.D.), Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160-7338
Address all correspondence and requests for reprints to: B. C. Paria, Department of Molecular and Integrative Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160-7338. E-mail: bparia{at}kumc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The heterogeneous cell types of the uterus respond uniquely to estrogen and/or P4 for the preparation of implantation. In the adult mouse uterus, estrogen stimulates proliferation of the epithelium, whereas in the stroma, this process requires both P4 and estrogen (7). A similar steroid hormonal regulation occurs in the mouse uterus during early pregnancy. Preovulatory ovarian estrogen directs epithelial cell proliferation on days 1 and 2, whereas on day 3, P4 from newly formed corpora lutea initiates stromal cell proliferation that is further stimulated by preimplantation estrogen secretion early on day 4. During implantation, epithelial cells undergo differentiation, while stromal cells undergo extensive proliferation and differentiation into decidual cells (7). In the mouse, uterine receptivity for implantation occurs only for a limited period during pregnancy or pseudopregnancy. In pregnant or pseudopregnant mice, the prereceptive uterus on day 3 becomes receptive on day 4 (the day of implantation), whereas by day 5 (as examined by blastocyst transfers), the uterus becomes refractory and fails to initiate implantation (2). Estrogen is essential for implantation in the P4-primed mouse uterus. Ovariectomy on the morning of day 4, before preimplantation ovarian estrogen secretion, results in blastocyst dormancy and failure in attachment reaction. This condition, known as delayed implantation, can be maintained by continued P4 treatment, but it is terminated by an injection of estrogen initiating blastocyst activation and implantation (2, 8). The mechanism by which estrogen initiates these responses in the P4-primed uterus is not known.
Because of the vasoactive, differentiating, and growth-promoting properties of histamine, its involvement in uterine vascular permeability changes and stromal decidualization during implantation has long been speculated (reviewed in Refs. 9, 10, 11). Mast cells are one of the major sources of histamine, and its release from these cells in the uterus by preimplantation ovarian estrogen secretion has been implicated in decidual cell reaction (12, 13, 14, 15, 16, 17). However, this theory was disputed by a number of investigators (reviewed in Refs. 9, 10, 11, 18). Further, normal implantation in mast cell deficient mice (19) and virtual absence of mast cells from the mouse endometrium or deciduum at the sites of implantation (20) argue against a role for mast cell-derived histamine in implantation. However, induction of implantation in delayed implanting rats by histamine with suboptimal doses of estrogen (21) still suggests that histamine is involved in implantation, and the source of histamine in the uterus could be other than the mast cells.
Histamine is a ubiquitous cell-to-cell mediator. It plays diverse roles in various pathophysiological processes, such as smooth muscle contraction, gastric acid secretion, cell growth, tumor growth, tissue regeneration, hematopoiesis, wound healing, neurotransmission, inflammation, and various reproductive functions. Although histamine is produced by mast cells in almost all tissues, this biogenic amine is also detected in a variety of other cell types, including basophils (22), platelets (23), enterochromaffin-like cells (24), endothelial cells (25), epithelial cells, and neurones (26). These studies have established that the levels of tissue histamine depend on the status of histidine decarboxylase (HDC, EC 4.1.1.22) activity, which is inducible by a variety of stimuli. The biosynthesis of histamine involves pyridoxal phosphate-dependent decarboxylation of L-histidine by HDC. This enzyme is specific for histidine and differs considerably from aromatic amino acid decarboxylases involved in biosynthesis of catecholamines and serotonin (27, 28, 29). HDC is a dimer of approximately 53- to 55-kDa subunits (30, 31) and its complementary DNA (cDNA) has been cloned from human and mouse tissues (32, 33, 34, 35). The molecular size of the recombinant HDC is approximately 74 kDa and is consistent with the predicted amino acid sequence. Although the mechanism regulating cleavage of 74 kDa to smaller species is not definitely known; a recent report suggests that an elastase-like enzyme is responsible for cleaving the 74-kDa HDC to its mature forms (36).
In the present investigation, we examined the temporal and cell-specific source of histamine and its regulation in the mouse uterus during the periimplantation period using molecular, cellular, and biochemical approaches. Contrary to the previous dogma, we demonstrate herein that uterine epithelial cells are a major source of HDC before implantation and that P4 is the primary regulator of this gene in the mouse uterus.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-fluoromethylhistidine was obtained from Mark Sharp and
Dohme Research Laboratories (Rahway, NJ). RU-486 was a gift from
Roussel-UCLAF (Romaineville, France).
L-(14C)histidine was obtained from NEN (Boston,
MA). Rabbit anti-HDC antibody was a generous gift from Dr. Kimio
Yatsunami (Pharmaceutical Basic Research Laboratories, Japan Tobacco
Inc., Kanagawa, Japan). All other reagents were acquired from Sigma or
Fisher Scientific (St. Louis, MO).
Animals and treatments
All experiments with animals were conducted in accordance with
NIH standards for the care and use of experimental animals. Virgin CD-1
female mice (48–60 days old, 20–25 g; Charles River
Laboratories, Raleigh, NC) were mated with fertile males of the
same strain. The morning of finding a vaginal plug was designated day 1
of pregnancy. Mice on days 1–4 were killed at 0830–0930 h, and
embryos were recovered from the reproductive tract to confirm
pregnancy. On days 5–8, mice were killed at 0900 h. Implantation
sites on days 5 and 6 were visualized by iv injection (0.1 ml/mouse) of
a Chicago blue dye solution (0.1% in saline). Implantation sites were
demarcated by discrete blue bands along the uterus (2). On days 7–8,
implantation sites are distinct and blue dye injection is not
required.
To induce and maintain delayed implantation, mice were ovariectomized at 0830–0900 h on day 4 of pregnancy and received daily injections of P4 from days 5–7 (2 mg/mouse). To terminate delayed implantation (2), the P4-primed delayed-implanting mice were given an injection of E2 (25 ng/mouse) on day 7 (the third day of delay). Mice were killed 12 h after treatment with the respective steroid hormones, and their uteri were collected for Northern blot hybridization.
To examine the effects of steroid hormones, mice were ovariectomized, without regard to the stages of estrous cycle, and rested for 10 days before receiving any treatment. Ovariectomized mice were injected with sesame oil (0.1 ml/mouse), P4 (1 mg/mouse), E2 (250 ng/mouse), and a combination of P4 and E2. To neutralize the effects of P4, mice were injected with RU-486 (400 µg/mouse) 30 min before the P4 injection (5, 37). All steroids and RU-486 were dissolved in sesame oil and injected sc. Mice were killed at various times after injections. Uteri were collected for RNA extraction, in situ hybridization, and immunocytochemistry.
Hybridization probes
A mouse cDNA encoding HDC was kindly provided by Dr A. Ichikawa
(Kyoto University, Kyoto, Japan). Because of its significant homology
with dopa decarboxylase and tryptophan decarboxylase (35), a small
fragment (350 bp) from the 3' terminus of the coding region with no
homology with other decarboxylases was released with BamHI
and EcoRI. This fragment was subcloned in pGEM7ZF(+) vector.
For Northern hybridization, an antisense 32P-labeled
complementary RNA (cRNA) probe was generated using SP6 polymerase. For
in situ hybridization, sense and antisense
35S-labeled cRNA probes were generated using T7 and SP6
polymerases, respectively. A part of the ribosomal protein L-7 (rpL7)
cDNA (246 bp, bases 359–604) was subcloned into pCR-Script vector
containing promotor for T7 polymerase and used as a template for
synthesis of 32P-labeled antisense rpL7 probe (38). All
probes had specific activities of about 2 x 109
dpm/µg.
Northern blot hybridization
Total RNA was extracted from whole uteri by a modified guanidine
thiocyanate procedure (5, 39). Poly(A)+ RNA was isolated by
oligo (dt)-cellulose column chromatography (40). Poly(A)+
RNA (2 µg) was denatured, separated by formaldehyde-agarose gel
electrophoresis, transferred, and cross-linked to the membrane by UV
irradiation (Spectrolinker, Spectronics Corp., Westbury, NY). Northern
blots were prehybridized, hybridized, and washed as described
previously (5, 37). The same blots were sequentially hybridized to HDC
and rpL7 probes, and the hybrids were detected by autoradiography.
In situ hybridization
In situ hybridization was performed as described
previously (5, 37). On specific days of pregnancy or at specific times
after hormone treatments, uterine horns were excised and cut into small
pieces or separated into implantation and interimplantation sites.
Frozen sections (10 µm) were mounted onto
poly-L-lysine-coated slides. When required, frozen sections
were cut serially to detect the sites of blastocysts. Sections were
fixed in 4% paraformaldehyde in PBS for 15 min at 4 C. After
prehybridization, uterine sections were hybridized to
35S-labeled HDC sense or antisense cRNA probes for 4 h
at 45 C. After hybridization and washing, the slides were incubated
with ribonuclease A (RNase A; 20 µg/ml) at 37 C for 15 min. RNase
A-resistant hybrids were detected after 1–3 days of autoradiography
using Kodak NTB-2 liquid emulsion. The slides were poststained with
hematoxylin and eosin.
Immunohistochemistry
Immunohistochemistry was performed as described previously (5, 37, 41). In brief, 4% paraformaldehyde-fixed paraffin sections (7
µm) were mounted onto poly-L-lysine-coated glass slides,
deparaffinized, and rehydrated in descending grades of ethanol,
followed by two washes in PBS (10 min each). Rabbit polyclonal
antipeptide antibodies to HDC (1:250 dilution) or affinity-purified
antihistamine antibodies (1:100 dilution) were used for immunostaining
using a Zymed-Histostain-SP Kit for rabbit primary antibodies
(Zymed Laboratories, San Francisco, CA). After immunostaining, sections
were lightly counterstained with hematoxylin. Red deposits indicated
the sites of immunoreactive proteins. Control sections were incubated
in preneutralized antibodies with a 100-fold molar excess of the
specific immunogens.
Western blot analysis
Western blot analysis was performed as described previously
(41). Pregnant day-4 uterine epithelium plus the underlying stroma
(LES) was collected by gently squeezing the uterus from the ovarian to
the cervical end by a pair of small curved forceps. LES, uterus minus
LES, or stomach corpus (positive control) was homogenized in buffer A
(10 mM Tris-HCl (pH 7.4), 250 mM sucrose, 2
mM EGTA, 10 µg/ml leupeptin, 20 µg/ml PMSF, and 10
µg/ml aprotinin and was centrifuged at 800 x g for
10 min at 4 C. The supernatants were recentrifuged for 1 h at
110,000 x g at 4 C. The supernatants (cytosolic
proteins, 60 µg/sample) were separated by SDS-PAGE (7.5%) under
reducing conditions and transferred to nitrocellulose membranes.
Membranes were incubated in 20% powdered milk (Carnation) dissolved in
TBST buffer (20 mM Tris-HCl and 0.15 M sodium
chloride (pH 7.4), 0.05% Tween-20) for 1 h at room temperature
for blocking nonspecific binding. They were then incubated in
antibodies to HDC diluted in 5% milk solution (1:1000) for 2 h at
room temperature, followed by washings in TBST buffer. Membranes were
incubated for 1 h at room temperature with the secondary antibody
(goat antirabbit IgG) conjugated with horseradish peroxidase (1:7500
dilution in 5% milk solution). They were then washed three times in
TBST buffer. Signals were detected by using an ECL kit (Amersham,
Arlington Heights, IL). Specificity of the reaction was determined by
preneutralizing the antibody with a 100-fold molar excess of
immunogenic peptide.
HDC assay
HDC activity was determined by the release of
14CO2 from
L-(14C)histidine (specific activity >300
mCi/mmol) in the presence of pyridoxal phosphate, as described
previously (42). In brief, LES or stomach corpus was collected in
ice-cold 10 mM Na-K-PO4 buffer (pH 7.2)
containing 5 mM dithiothreitol (DTT), 10
mM EDTA, 5 mM NaF, 0.025% Triton X-100, PMSF
(5 µg/ml), and leupeptin (1 µg/ml). LES was sonicated, and other
tissues were homogenized. After being centrifuged at 800 x
g for 10 min at 4 C, supernatants were centrifuged at
110,000 x g for 1 h. Aliquotes of the
supernatants were used for HDC assay.
Measurement of histamine content
Tissues removed after perfusion of mice with cold saline were
boiled for 5 min in 2 ml distilled water, were homogenized, and were
centrifuged at 10,000 x g for 20 min. The supernatants
were analyzed for their histamine content by the radioenzymatic method,
quantifying radiolabeled methylhistamine formed in the presence of
3H-S-adenosyl methionine and purified N-methyl
transferase (43). Specificity of the reaction was assessed by
preincubating parallel samples with diamine oxidase (histaminase),
which eliminated measurable histamine in all samples.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
). Similar
results were obtained using a rat HDC cRNA probe (data not shown). The
levels of HDC mRNA in whole uterine poly(A)+ RNA samples
were highest on days 3 and 4, followed by a gradual decline from days
5–8 of pregnancy (Fig. 1A). These results suggest that rising plasma
P4 levels (46) probably contributed to higher HDC mRNA
levels on days 3 and 4 of pregnancy. Because P4 priming is
essential for the preparation of the uterus for estrogen to initiate
implantation, we examined the expression of HDC mRNA in the
P4-primed delayed-implanting uterus before and after an
injection of E2 (25 ng/mouse). Levels of uterine HDC mRNA
under these treatment conditions were comparable with those observed on
day 4 of pregnancy (Fig. 1B), suggesting again the regulation of
uterine HDC mRNA by P4.
|
). These results are consistent with
those of Northern blot hybridization. Furthermore, the signals were
present throughout the luminal epithelium regardless of the location of
blastocysts. After implantation on day 5, autoradiographic signals were
lower in the luminal epithelium surrounding the blastocysts, and no
signals were observed in decidualizing stroma on days 5–8. On days
6–8, the remaining luminal epithelium at the mesometrial pole
exhibited signals for this mRNA (Fig. 2). The accumulation persisted in
the luminal epithelium at the interimplantation sites (data not shown).
Sections hybridized with the sense probe did not exhibit any positive
signals (data not shown).
|
). HDC mRNA was very low in
ovariectomized uterine RNA samples. However, a single injection of
P4 rapidly up-regulated the levels within 6 h and
maintained the levels through 24 h (Fig. 3A). An injection of
E2 neither induced HDC mRNA (Fig. 3B) nor antagonized
P4-induced up-regulation (Fig. 3C). P4
induction of HDC mRNA was considerably attenuated by prior treatment
with RU-486 (Fig. 3D), suggesting that P4 effects are
mediated via its receptors.
|
).
|
). The
immunostaining was greatly reduced when the primary antibodies were
preneutralized with specific immunogens. Western blotting detected a
band of approximately 54 kDa, in cytosolic extracts of the stomach and
LES, but not in uterus minus the LES (Fig. 6A). This is consistent with the HDC
activity described below. The 54-kDa bands were not detected when
preneutralized antibodies with an excess of antigenic peptide were used
(Fig. 6B). This 54-kDa band was reported previously in other tissues as
a mature HDC protein (31, 36, 47).
|
|
).
Double-reciprocal plots were produced using ENZFITTER, a nonlinear
regression data analysis IBM-PC program. HDC activity was completely
inhibited in cytosolic extracts of stomach or LES by 10
µM -fluoromethylhistidine, an inhibitor of HDC (data
not shown). HDC activity was not detected in cytosolic extracts of the
uterus without the LES (data not shown). Total uterine histamine levels
gradually increased from day 1 through day 4 of pregnancy (Table 1). After embryo implantation, tissue
histamine levels were lower in the implantation sites, as compared with
those at the interimplantation sites. These results are consistent with
HDC mRNA levels. The HDC activity and levels of histamine are lower in
uterine extracts, compared with those in the stomach. This could be
caused by the higher turnover of histamine, HDC, and/or the presence of
an inhibitor of HDC activity in the uterus.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The effects of P4 and E2 could be either synergistic, antagonistic, or distinctive, with respect to various uterine functions and gene expression in a temporal and cell-specific manner. For example, synergistic and antagonistic effects of P4 and E2 on epithelial and stromal cell proliferation, differentiation, and gene expression are well-documented (5, 7, 53, 54, 55). However, the steroid hormonal regulation of the uterine HDC is neither synergistic nor antagonistic; rather, the regulation is distinctive to P4. Because both P4 and estrogen are essential for implantation in the mouse, synergistic, antagonistic, and/or distinctive effects of these steroids at the molecular and cellular level seem to be essential for successful implantation. The up-regulation of HDC in the luminal epithelium by P4 is the first example of a true distinctive function that is not antagonized or synergised by E2 at the molecular level.
Because the up-regulation of HDC occurs in the uterine epithelium of
pregnant (Fig. 1
) or pseudopregnant (data not shown) mice on day 4, the
presence of blastocysts is not required for the expression of this
enzyme in the uterus. Although, P4 seems to be the primary
regulator of HDC in the preimplantation uterus, the down-regulation of
this gene at the implantation sites on days 5–8 of pregnancy, when
P4 levels are still rising, probably reflects the gradual
loss of the epithelium initiated by the implanting blastocysts. The
sustained expression of epithelial HDC at the interimplantation sites
is consistent with this observation. Because E2 fails to
antagonize P4 induction of HDC, the rising P4
levels with small elevation of estrogen levels are not likely to be
responsible for this down-regulation. These results are consistent with
those obtained with the delayed implanting uterus.
The importance of histamine in blastocyst implantation and decidualization has been a subject of intense debate since the hypothesis was formulated that histamine released from the uterine mast cells by the preimplantation ovarian estrogen secretion is responsible for initiating decidual cell reaction (12, 13, 14, 15, 56). In this respect, several studies showed that the number of mast cells and uterine content of histamine reach a maximum during the preimplantation period but decline after initiation of implantation. However, the apparent absence of mast cells in the mouse endometrium during early pregnancy has raised doubts regarding a role for mast cells in generating uterine histamine that could be important for implantation (20). In contrast, the presence of histamine in the uterus of ovariectomized steroid-treated mast cell-deficient W/Wv mice establishes that uterine cells, other than resident mast cells, are the source of histamine (57) and could be important for implantation. Our present results establish that uterine epithelial cells are the major source of histamine in the mouse uterus. This may explain why implantation is normal in mast cell-deficient mice. Further studies regarding the status of histamine receptors in the uterus and embryo are warranted to better understand the importance of histamine in implantation.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Present address: Department of Biochemistry, Bose Institute,
Calcutta 700054, India.
Received February 23, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
precursors in the mouse
uterus during the periimplantation period and after steroid hormone
treatments. Biol Reprod 50:481–491[Abstract]
This article has been cited by other articles:
 |
|
 |
|
  S. R. Hansson, B. Bottalico, V. Noskova, and B. Casslen Monoamine transporters in human endometrium and decidua Hum. Reprod. Update, March 1, 2009; 15(2): 249 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Maintz, V. Schwarzer, T. Bieber, K. van der Ven, and N. Novak Effects of histamine and diamine oxidase activities on pregnancy: a critical review Hum. Reprod. Update, September 1, 2008; 14(5): 485 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G Lea and O. Sandra Immunoendocrine aspects of endometrial function and implantation Reproduction, September 1, 2007; 134(3): 389 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, I. M. Wolf, H. Chen, S. Periyasamy, Z. Chen, W. Yong, S. Shi, W. Zhao, J. Xu, A. Srivastava, et al. FK506-Binding Protein 52 Is Essential to Uterine Reproductive Physiology Controlled by the Progesterone Receptor A Isoform Mol. Endocrinol., November 1, 2006; 20(11): 2682 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pan, L. Zhu, Y. Deng, and J. W. Pollard Microarray Analysis of Uterine Epithelial Gene Expression during the Implantation Window in the Mouse Endocrinology, October 1, 2006; 147(10): 4904 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Khatua, X. Wang, T. Ding, Q. Zhang, J. Reese, F. J. DeMayo, and B. C. Paria Indian Hedgehog, But Not Histidine Decarboxylase or Amphiregulin, Is a Progesterone-Regulated Uterine Gene in Hamsters Endocrinology, September 1, 2006; 147(9): 4079 - 4092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Noskova, B. Bottalico, H. Olsson, A. Ehinger, R. Pilka, B. Casslen, and S. R. Hansson Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2 Mol. Hum. Reprod., August 1, 2006; 12(8): 483 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Niklaus and J. W. Pollard Mining the Mouse Transcriptome of Receptive Endometrium Reveals Distinct Molecular Signatures for the Luminal and Glandular Epithelium Endocrinology, July 1, 2006; 147(7): 3375 - 3390. [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]
|
|
|
|
 |
|
 C. Mondillo, Z. Patrignani, C. Reche, E. Rivera, and O. Pignataro Dual Role of Histamine in Modulation of Leydig Cell Steroidogenesis via HRH1 and HRH2 Receptor Subtypes Biol Reprod, November 1, 2005; 73(5): 899 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tranguch, J. Cheung-Flynn, T. Daikoku, V. Prapapanich, M. B. Cox, H. Xie, H. Wang, S. K. Das, D. F. Smith, and S. K. Dey From The Cover: Cochaperone immunophilin FKBP52 is critical to uterine receptivity for embryo implantation PNAS, October 4, 2005; 102(40): 14326 - 14331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Jeong, K. Y. Lee, I. Kwak, L. D. White, S. G. Hilsenbeck, J. P. Lydon, and F. J. DeMayo Identification of Murine Uterine Genes Regulated in a Ligand-Dependent Manner by the Progesterone Receptor Endocrinology, August 1, 2005; 146(8): 3490 - 3505. [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]
|
|
|
|
|
|
Y.-P. Cheon, X. Xu, M. K. Bagchi, and I. C. Bagchi Immune-Responsive Gene 1 Is a Novel Target of Progesterone Receptor and Plays a Critical Role during Implantation in the Mouse Endocrinology, December 1, 2003; 144(12): 5623 - 5630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chen, D. Zhang, and J. W. Pollard Progesterone Regulation of the Mammalian Ortholog of Methylcitrate Dehydratase (Immune Response Gene 1) in the Uterine Epithelium during Implantation through the Protein Kinase C Pathway Mol. Endocrinol., November 1, 2003; 17(11): 2340 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Richard, J. Gao, N. Brown, and J. Reese Aquaporin Water Channel Genes Are Differentially Expressed and Regulated by Ovarian Steroids during the Periimplantation Period in the Mouse Endocrinology, April 1, 2003; 144(4): 1533 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. M. Yao, H. Lim, D. J. Schust, S. E. Choe, A. Farago, Y. Ding, S. Michaud, G. M. Church, and R. L. Maas Gene Expression Profiling Reveals Progesterone-Mediated Cell Cycle and Immunoregulatory Roles of Hoxa-10 in the Preimplantation Uterus Mol. Endocrinol., April 1, 2003; 17(4): 610 - 627. [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]
|
|
|
|
 |
|
 O. M. Conneely, B. Mulac-Jericevic, F. DeMayo, J. P. Lydon, and B. W. O'Malley Reproductive Functions of Progesterone Receptors Recent Prog. Horm. Res., January 1, 2002; 57(1): 339 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Reese, S. K. Das, B. C. Paria, H. Lim, H. Song, H. Matsumoto, K. L. Knudtson, R. N. DuBois, and S. K. Dey Global Gene Expression Analysis to Identify Molecular Markers of Uterine Receptivity and Embryo Implantation J. Biol. Chem., November 16, 2001; 276(47): 44137 - 44145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X Zhao, W Ma, S. Das, S. Dey, and B. Paria Blastocyst H(2) receptor is the target for uterine histamine in implantation in the mouse Development, January 6, 2000; 127(12): 2643 - 2651. [Abstract] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
