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PubMed1955

The depression of growth of the uterus, adrenals, and ovaries by fluorinated steroids in the pregnane series.

Progesterone, 5-pregnene-3,20-dione, and desoxycorticosterone were found to be partial but significant inhibitors of estrone-induced growth of the uterus of hypophysectomized rats but they did not depress the amount of growth elicited by testosterone. The presence of both the 2-carbon side chain at position 17 and an oxygenated function at position 3 is necessary for the inhibitory activity of progesterone. The introduction of a hydroxyl group in the progesterone molecule at positions 6 (beta), 11 (alpha), 16 (alpha) or 17 (alpha) destroyed its growth-inhibitory activity. 11beta-Hydroxyprogesterone is weaker than progesterone in the inhibition of estrone-induced uterine growth; unlike progesterone it has the capacity to depress growth elicited by testosterone. The introduction of a flourine atom in the 9 (alpha) position resulted in a striking increase of the growth-inhibitory activity of 11beta-hydroxyprogesterone and hydrocortisone. 9alpha-Flouro-11beta-hydroxyprogesterone is a partial but significant inhibitor of growth of the uterus in hypophysectomized rats injected simultaneously with large doses of estrone or testosterone. It is more powerful than progesterone in transforming the vaginal epithelium to mucus cells in the presence of estrone. Administered alone, the only detectable growth was a slight increase in size of the preputial glands. 9alpha-Flouro-11beta-hydroxyprogesterone suppresses in part the growth of the adrenals, ovaries, and uterus in intact rats at a dose level which does not cause loss of body weight or inhibit body growth. Many rats treated with this compound in small amount had extensive mucification of the vagina resembling that of late pregnancy.

Adrenal Cortex↗
PubMed1996

The involvement of interleukin (IL)-15 in regulating the differentiation of granulated metrial gland cells in mouse pregnant uterus.

Previous studies have suggested that granulated metrial gland (GMG) cells are bone marrow-derived lymphoid cells, which differentiate in situ in the mouse pregnant uterus into natural killer (NK)-like cells. Similar to NK cells, GMG cells express an abundant level of cytolytic mediators such as perforin. The factor(s) regulating the differentiation of GMG cells remain(s) to be identified, although cytokines previously implicated in the stimulation/activation of NK cells (e.g., IL-2, IL-6, IL-7, and IL-12) can be considered as potential candidates. Recently, IL-15, a novel cytokine, which displays biological activities similar to IL-2, has also been shown to be capable of activating NK cells. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we have demonstrated in the present study that IL-15 and its cognate receptor, but not the other cytokines, are expressed in the mouse pregnant uterus, with a time course concomitant with those of cytolytic mediators in differentiated GMG cells. Moreover, IL-15, though not IL-2, is capable of inducing the expression of perforin and granzymes in pregnant uterine tissues explanted in vitro. Data obtained from in situ hybridization study have suggested that the macrophages present in the pregnant uterus may be responsible for the production of IL-15. These results suggest that IL-15 is involved in regulating the differentiation of GMG cells during mouse pregnancy.

Animals↗
PubMed2001

Efficient liposome-mediated gene transfection and expression in the intact human uterus.

Although gene therapy has been used for correction of metabolic defects in diseases such as cystic fibrosis, as adjuvant treatment in cancer, and in the treatment of infectious diseases, there has been no report of gene transfer to the intact female reproductive tract. We assessed the ability to transfect the human uterus ex vivo and thereby evaluate the applicability of gene therapy to gynecology. The uterine lumen was accessed transcervically, using an intrauterine insemination catheter. pcDNA3.1 plasmid containing the Escherichia coli lacZ reporter gene was delivered to each uterus via liposome-mediated transfection. Control uteri were transfected with empty pcDNA3.1. Immunohistochemical analysis revealed beta-galactosidase expression in the lacZ-treated uteri in endometrial epithelial cells, endometrial stromal cells, and myometrium to a depth of 1.75 cm from the endometrial-myometrial junction. Highest expression was seen in endometrial glandular epithelial cells, with significant expression in the stroma and adjacent myometrium. Each of these cell types in the control uteri showed no beta-galactosidase expression. Successful gene transfection and expression in the intact human uterus can be accomplished easily, rapidly, and efficiently. Gene therapy may have wide applicability in the treatment and study of gynecologic disease.

Adult↗
PubMed1979

Actions of hormones on the uterus and effect on conceptus development.

The process of reproduction in the mammalian female involves interactions between gonadal and placental steroids and, possibly, protein hormones such as placental lactogen, and the uterine endometrium. These interactions are discussed relative to available data from pigs and with the understanding that the concepts presented may not be directly applicable to other species. Swine embryos enter the uterus for continued development beyond the early blastocyst stage and, within the uterus, the spherical blastocyst, of about 2 mm diameter on day 12, undergoes rapid elongation to an organism of about 1 m in length by day 15 of pregnancy. During this period of elongation, the blastocyst appears to provide the chemical signal, presumably unconjugated estrogens, that allows for corpora lutea (CL) maintenance (luteostatic effect) and, therefore, continued production of progesterone by the CL which is essential for pregnancy. Estrogens from the blastocyst may exert their luteostatic effect on the uterus by causing prostaglandin F2 alpha, the presumed porcine uterine luteolysin, to be secreted in an exocrine (toward the uterine lumen) rather than an endocrine (toward the endometrial stroma and vasculature) direction during pregnancy. Consequently, prostaglandin F2 alpha is sequestered in the uterine lumen and does not become available, via the utero-ovarian vasculature, to exert its luteolytic effect. The potential steroid precursor(s) available to the trophoblast for estrogen synthesis appear to be produced through endometrial conversion of progesterone to unconjugated androgens, e.g., androstenedione and testosterone, and conjugated estrogens, e.g., estrone-sulfate and estradiol-sulfate. The estrogens may, in concert with progesterone and possibly other hormones, placental lactogen for example, act locally, i.e., at the site of placentation to: result in a luteostatic effect; increase uterine blood flow; enhance water, electrolyte and substrate (carbohydrate and amino acid) transport to the site of placentation and across the placenta; affect synthesis and secretion of macro-molecules (histotroph) by the uterine glands that serve as enzymes and (or) carrier molecules and control or modulate physiological and (or) biochemical events essential to placental and fetal development that are not understood.

Animals↗
PubMed1997

Anatomical variation in the rudimentary horns of a unicornuate uterus: implications for laparoscopic surgery.

A case of laparoscopic excision of a rudimentary horn is presented. The anatomical features of this case are contrasted with others in the published literature. A 23 year old nulligravida presented with severe dysmenorrhoea and a pelvic mass. At laparoscopy a unicornuate uterus with a rudimentary horn was identified. The patient had stage III endometriosis. The rudimentary horn was attached to the unicornuate uterus by a band of tissue. The blood supply was identified within this band of tissue. The rudimentary horn was removed laparoscopically with no complications. There are two anatomical variations in the attachment of the rudimentary horn to the unicornuate uterus. Knowledge of both types is important to avoid complications such as bleeding and possible compromise of myometrial wall thickness.

Adult↗
PubMed1997

Local relaxin biosynthesis in the ovary and uterus through the oestrous cycle and early pregnancy in the female marmoset monkey (Callithrix jacchus).

The pattern of peripheral serum concentration for the peptide hormone relaxin in women points to the possibility of an interesting paracrine function in the cycle and early pregnancy. In order to investigate this physiology in detail, it was decided to examine local relaxin biosynthesis in an established primate model for human female reproductive function, the marmoset monkey (Callithrix jacchus). In this initial study relaxin biosynthesis was assessed using a combination of molecular and immunological techniques through the oestrous cycle in the marmoset monkey. The nucleotide sequence of the full-length relaxin gene transcript was cloned from the marmoset ovary and found to be closely homologous to that of the human H2 relaxin. Using gene specific probes derived from this sequence, RNase protection assays, reverse transcription-polymerase chain reaction (RT-PCR) assays and in-situ hybridization, showed relaxin gene expression within the ovary in theca cells and corpora lutea in the oestrous cycle, increasing in early pregnancy. Relaxin gene expression was also identified at a low level in the uterus and placenta, and at a higher level in the prostate in the male marmoset monkey. Using two different relaxin-specific antisera, relaxin-like immunoreactivity was observed in the ovary with a pattern of distribution coincident with that obtained by in-situ hybridization. Immunoreactivity was also found in the non-pregnant uterus, within the endometrial epithelium of the late proliferative phase and increasing within the glands through the secretory phase. Taken together, the pattern of relaxin peptide and mRNA expression show there is the basis for local relaxin physiology within the ovarian follicle and corpus luteum, and within the uterus during the oestrous cycle in this new world monkey.

Amino Acid Sequence↗
PubMed1998

Hysteroscopic metroplasty in diethylstilboestrol-exposed and hypoplastic uterus: a report on 24 cases.

The aim of this study was to determine the feasibility and safety of hysteroscopic metroplasty in cases of diethylstilboestrol-exposed and hypoplastic malformed uterus. Twenty-four patients were referred for primary infertility (n = 9), secondary infertility (n = 1) or infecundity (n = 14). Fifteen had been exposed to diethylstilboestrol in utero. All patients had a hypoplastic uterus and/or uterine deformity as seen by hysterosalpingography and each served as their own control. All patients underwent hysteroscopic metroplasty. Outcome measures included postoperative hysterosalpingography and the ability to conceive and to carry pregnancy to live birth. Postoperative hysterosalpingograms revealed improvement in 23 cases; the final result was considered excellent in 15 cases and 11 pregnancies occurred. The abortion rate decreased from 88% in previous pregnancies to 12.5%, and the rate of term deliveries increased from 3% to 87.5%. Ten patients were delivered after 30 weeks' gestation of healthy infants and one delivered more prematurely. Six deliveries were normal and four required a Caesarean section. We conclude that hysteroscopic metroplasty gives good results. This technique can be used in women with diethylstilboestrol-exposed or hypoplastic malformed uterus, suffering from severe infertility, recurrent pregnancy loss or implantation failures in an in-vitro fertilization programme.

Adult↗
PubMed1999

Laparoscopic hemi-hysterectomy in treatment of a didelphic uterus with a hypoplastic cervix and obstructed hemivagina.

Maldevelopment of the Müllerian duct system may result in various urogenital anomalies including didelphic uterus with a hypoplastic cervix and obstructed hemivagina. We report a patient with this anomaly who was treated by laparoscopic hemi-hysterectomy and hysteroscopic resection of hemivagina. A 17 year old patient who had complained of vaginal pus-like discharge on and off for 1 year was diagnosed by MRI to have a double uterus with obstructed right hemivagina and ipsilateral renal agenesis. After hysteroscopic identification of hypoplasia of the right uterine cervix, laparoscopic resection of the right uterus and right Fallopian tube and hysteroscopically assisted resection of the vaginal septa were performed successfully. From our experience, combined laparoscopy and hysteroscopy may be an efficacious alternative in the management and diagnosis of Müllerian anomalies.

Adolescent↗
PubMed2004

Preferential transfer of endogenous ovarian steroid hormones to the uterus during both the follicular and luteal phases.

BACKGROUND: Ovarian steroids are thought to be released into the systemic circulation and reach the uterus via the uterine arteries. However, results of experimental and clinical studies suggest the existence of local transfer of steroids from the ovary to the uterus. This study aimed to verify the existence of preferential distribution of ovarian steroids to the uterus in the two phases of the menstrual cycle. METHODS: We performed parallel measurements of serum levels of estradiol and progesterone in the systemic circulation (arterial and venous) and in the uterine vessels in two groups of cycling women; one group were in the follicular phase (six women) and the other group were in the luteal phase (10 women) of the menstrual cycle. RESULTS: Both in the follicular phase and in the luteal phase groups, mean estradiol levels in the uterine blood were significantly higher than in both sides of the systemic circulation (F = 7.30, df = 15, P < 0.006; and F = 4.70, df = 27, P < 0.02). Similar results were obtained in the luteal phase group for progesterone (F = 9.38, df = 27, P < 0.0001). Both estradiol and progesterone levels in arterial and venous systemic blood were similar. CONCLUSIONS: The results of this study demonstrate that ovarian steroid levels are significantly higher in the uterine vessels than in both sides of the systemic blood circulation, and strongly suggest the existence in the female pelvis of mechanisms of local distribution of ovarian hormones.

Adult↗
PubMed2005

A dominant ovarian follicle induces unilateral changes in the origin of the blood supply to the tubal corner of the uterus.

BACKGROUND: The blood supply to the tubal corner of the uterus may originate from the uterine and ovarian arteries. The border of supply from the arteries has been found to move in young women; the change seemed dependent on ovarian steroid production. The present work investigated whether the border of supply could differ between the two sides of the uterus in the same woman having one dominant follicle (>10 mm). METHODS: Vagina was flushed with saline of room temperature in 15 women with a dominant follicle >10 mm. The temperature was measured in the mid-uterine lumen and in the tubal corner of the uterus at 2, 5 and 7 min after starting cooling. The investigation was repeated 30 min later measuring the temperature in the other tubal corner. RESULTS: The temperature decrease was, as found in previous investigations, more pronounced in the uterine cavity than in the tubal corners. However, a difference was found between the two tubal corners. At all measurement times the decrease was significantly smaller in the tubal corner corresponding to the dominant follicle than in the contralateral side. CONCLUSIONS: In our model, 'cold' is transferred from the vaginal venous blood to the uterine artery and the cooling defines the supply area of the uterine artery. Therefore, the results indicate that the area of supply from the ovarian artery in the tubal corner ipsilateral to the dominant follicle is greater than that in the contralateral side. It is possible to speculate that this difference is related to the hormonal production of the dominant follicle.

Adult↗
PubMed2001

Characterization of relaxin binding in the uterus of the marmoset monkey.

The ovarian peptide hormone relaxin (RLX) plays an important role in the regulation of the endometrium both during the cycle and in early pregnancy. RLX interacts with specific receptors on endometrial stromal cells causing these to decidualize. In order to characterize the molecules with which RLX interacts in the primate uterus, a methodology based on a fully bioactive preparation of biotinylated porcine RLX was applied to cryosections of the uterus of female marmoset monkeys. Specific RLX binding was weakly detected in the proliferative phase in isolated endometrial stromal cells. In the secretory phase, the positively reacting cells increased in staining intensity and in number and also included some epithelial cells. Further increases occurred in pregnancy, but RLX binding in the endometrium decreased at the end of the cycle if pregnancy did not occur. The myometrium showed weak staining which did not vary through the cycle, but increased in pregnancy. Electrophoretic analysis of the RLX-binding moieties in these tissue sections indicated that a protein of approximately 40 kDa was the principal RLX-binding molecule, while minor specific bands were detectable at approximately 100 and approximately 200 kDa. The binding of biotinylated RLX could be specifically suppressed by co-incubation with unlabelled RLX, but not by insulin, IGF-I or biotin. This technique therefore allows the detection and molecular characterization of specific RLX binding in the primate uterus. In the marmoset monkey, the pattern of specific binding closely reflects the RLX-dependent physiology during implantation and early pregnancy, implying the probable involvement of a specific RLX receptor.

Animals↗
PubMed2002

Expression and regulation of the fatty acid amide hydrolase gene in the rat uterus during the estrous cycle and peri-implantation period.

Fatty acid amide hydrolase (FAAH) is involved in embryo development and implantation. Sex hormones down-modulate FAAH activity in the mouse uterus. However, the regulation of the FAAH gene in the uterus is unknown. Our results showed that FAAH mRNA is localized to uterine epithelial cells and circular myometrium during the estrous cycle. In ovariectomized rats, estradiol (E2) plus progesterone (P4) increased FAAH levels in both epithelial cells and circular myometrium. Interestingly, during the implantation period, FAAH mRNA was detected not only in epithelial cells and circular myometrium, but also in the primary decidual zone surrounding the implanting embryo on day 6 and in whole decidualized stromal cells on day 7. Its levels in the stromal cells were markedly higher at the implantation sites than at the inter-implantation sites on days 6 and 7. When implantation was delayed and then induced by E2 or E2 plus P4, FAAH mRNA levels were significantly increased in subepithelial stromal cells and circular myometrium, indicating that blastocyst activation and initiation of implantation in rats requires higher expression of the FAAH gene in subepithelial stromal cells and circular myometrium. In conclusion, the expression of FAAH mRNA is different in the non-pregnant and pregnant rat uterus and sex hormones up-regulate FAAH gene expression.

Amidohydrolases↗
PubMed2003

Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector.

The uterus is obviously critical in implantation, development of the fetus and parturition. Endometrial cancer derived from endometrial epithelium is one of the common malignancies in the female reproductive tract. In order to clarify the local mechanisms of reproductive physiology and establish a non-systemic therapeutic strategy for reproductive failure as well as for endometrial cancer, we applied haemagglutinating virus of Japan envelope (HVJ-E) vector to in-vivo gene transfer into the uterine cavity of IVCS mice. Injection of HVJ-E vector into mouse uterine cavity on day 1.5 post coitum (p.c.) introduced a reporter gene approximately 120-fold more efficiently than introduction using the cationic liposome method. The expression of the introduced gene continued for at least 3 days. The plasmid vector was localized in the endometrial epithelium, whereas oligo deoxynucleotides were distributed throughout the epithelium, stromal cells and myometrium. HVJ-E vector did not affect the pregnancy rate, course of pregnancy, litter size, fetal growth in utero or parturition, and did not transfect the exogenous gene to the fetus. These results indicate that gene transfer into the uterus using HVJ-E vector is highly efficient and safe during pregnancy, and results in a well controlled distribution of the exogenous DNA. We believe that this procedure should be widely applicable for investigations of reproductive physiology as well as for methods of local gene therapy in the uterus.

Animals↗
PubMed2004

Mouse blastocysts release a lipid which activates anandamide hydrolase in intact uterus.

Anandamide (N-arachidonoylethanolamine, AEA) is a major endocannabinoid, known to impair mouse pregnancy and embryo development and to induce apoptosis in blastocysts. Here we show that mouse blastocysts rapidly (within 30 min of culture) release a soluble compound, that increases by approximately 2.5-fold the activity of AEA hydrolase (fatty acid amide hydrolase, FAAH) present in the mouse uterus, without affecting FAAH gene expression at the translational level. This "FAAH activator" was produced by both trophoblast and inner cell mass cells, and its initial biochemical characterization showed that it was fully neutralized by adding lipase to the blastocyst-conditioned medium (BCM), and was potentiated by adding trypsin to BCM. Other proteases, phospholipases A(2), C or D, DNAse I or RNAse A were ineffective. BCM did not affect the AEA-synthesizing phospholipase D, the AEA-binding cannabinoid receptors, or the selective AEA membrane transporter in mouse uterus. The FAAH activator was absent in uterine fluid from pregnant mice and could not be identified with any factor known to be released by blastocysts. In fact, platelet-activating factor inhibited non-competitively FAAH in mouse uterus extracts, but not in intact uterine horns, whereas leukotriene B(4) or prostaglandins E(2) and F(2)alpha had no effect. Overall, it can be suggested that blastocysts may protect themselves against the noxious effects of uterine endocannabinoids by locally releasing a lipid able to cross the cell membranes and to activate FAAH. The precise molecular identity of this activator, the first ever reported for FAAH, remains to be elucidated.

Amidohydrolases↗
PubMed1981

Cytoplasmic estrogen receptor system of gilt uterus. Partial purification of component B labeled with [14C]iodoacetic acid.

Analysis of the cytoplasmic estrogen receptor (ER) system of gilt uterus by protecting ER from proteolysis showed that the ER system of gilt uterus is similar to that of cow uterus described previously. There was only one native unit molecule [native "4S" ER (sedimentation coefficient, 4.5S; Stokes radius, 45 A; molecular weight, 82,000)] with specific affinity towards estradiol. This molecule was further designated as vero-ER. "8S" ER-forming factor [("8S"ER)-FF] (Stokes radius, 51 A) was separated from the cytosol under hypotonic (low salt) conditions, and this was further dissociated into component A ["5S" ER-forming factor, ("5S"ER)-FF] (Stokes radius, 37 A) and component B (Stokes radius, 18.5 A) in the presence of sodium thiocyanate. Vero-ER was proteolyzed in the absence of Ca2+ ion by a cytoplasmic protease into modified "4S" ER (sedimentation coefficient, 4.5S; Stokes radius, 35 A; molecular weight, 65,000) which was further designated as secto-ER. The constituents of the cytoplasmic ER system of cow and gilt uteri cross-reacted with each other to undergo similar molecular assembly as in their own systems. When analyzed for various uterine specimens, fluctuation of ("8S"ER)-FF-level (1-50 unit/g tissue) was more remarkable than that of ER-level (3-6 x (10(-12) mol/g tissue). Component B labeled with [14C]iodoacetic acid was purified over 1,500-fold. Mixture of vero-ER and component B labeled with [14C]iodoacetic acid formed "6S' ER with 14C-activities under hypotonic conditions. This clearly excluded the possibility that component B is a catalyzer of self-association (dimerization) of vero-ER.

Animals↗
PubMed2004

Effect of genistein as a selective estrogen receptor beta agonist on the expression of Calbindin-D9k in the uterus of immature rats.

Genistein, a phytoestrogen possessing a high affinity for estrogen receptor beta (ERbeta), is of increasing interest because of its possible influence on the physiology of mammalian reproductive tracts. Although estrogen has been demonstrated to regulate Calbindin-D9k (CaBP-9k) in the rat uterus as with other calcium binding proteins, the role of ERbeta on the modulation of CaBP-9k remains to be elucidated. To elucidate the effect of genistein as a selective ERbeta agonist on uterine expression of CaBP-9k mRNA and protein, immature female rats were injected with genistein daily for three consecutive days in a dose-dependent (0.4, 4, and 40 mg/kg/day) and time-dependent (40 mg/kg/day; 3, 6, 12, 24, 48, and 72 h) manner. Then, the expression of CaBP-9k mRNA and protein was analyzed by Northern hybridization and Western blot, respectively, in the absence or presence of ICI 182,780 (ICI), an estrogen antagonist. In addition, the protein levels of ERalpha and ERbeta and mRNA level of progesterone receptor (PR) were further measured following genistein treatment to elucidate which of ERs is involved in CaBP-9k modulation. In a dose-dependent experiment, the highest dose of genistein (40 mg/kg/day) for 3 days significantly induced uterine CaBP-9k protein as 17beta-estradiol (E2) did. In addition, its maximal mRNA expression was observed at 3 and 6 h, and it returned to control level at 24 h in a time-dependent experiment. In parallel with its mRNA level, the protein level of CaBP-9k was significantly induced by genistein at 3 h and sustained up to 48 h. The pretreatment with ICI, followed by genistein or E2, completely blocked genistein- and E2-induced CaBP-9k protein in the uterus of immature rats. Interestingly, genistein was demonstrated to induce ERalpha protein, but not ERbeta and PR mRNA, an E2-responsive gene, in this tissue. These results imply that genistein, an ERbeta ligand, may regulate CaBP-9k gene through ERalpha pathway. Taken together, the present study demonstrated that genistein enhanced CaBP-9k gene via ERalpha in the uterus of immature rats, suggesting that ERalpha may be a key mediator in uterine CaBP-9k gene induction in immature rats.

Animals↗
PubMed2002

Spatial and temporal patterns of expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 messenger RNA and glucocorticoid receptor protein in the murine placenta and uterus during late pregnancy.

To gain insight into the role of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes and actions of glucocorticoids in the murine placenta and uterus, the expression pattern of the mRNA for 11beta-HSD1 and 11beta-HSD2 and the glucocorticoid receptor (GR) protein were determined from Embryonic Day 12.5 (E12.5, term = E19) to E18.5 by in situ hybridization and immunohistochemistry, respectively. Consistent with its putative role in regulating the transplacental passage of maternal glucocorticoid to the fetus, 11beta-HSD2 mRNA was highly expressed in the labyrinthine zone (the major site of maternal/fetal exchange) at E12.5, and its level decreased dramatically at E16.5, when it became barely detectable. Remarkably, the silencing of 11beta-HSD2 gene expression coincided with the onset of 11beta-HSD1 gene expression in the labyrinth at E16.5 when moderate levels of 11beta-HSD1 mRNA were detected and maintained to E18.5. By contrast, neither 11beta-HSD1 mRNA nor 11beta-HSD2 mRNA were detected in any cell types within the basal zone from E12.5 to E18.5. Moreover, the expression of 11beta-HSD1 and 11beta-HSD2 in the decidua exhibited a high degree of cell specificity in that the mRNA for both 11beta-HSD1 and 11beta-HSD2 was detected in the decidua-stroma but not in the compact decidua. A distinct pattern was also observed within the endometrium where the mRNA for 11beta-HSD1 was expressed in the epithelium, whereas that for 11beta-HSD2 was confined strictly to the stroma. By comparison, the expression of GR in the placenta and uterus was ubiquitous and unremarkable throughout late pregnancy. In conclusion, the present study demonstrates for the first time remarkable spatial and temporal patterns of expression of 11beta-HSD1 and 11beta-HSD2 and GR in the murine placenta and uterus and highlights the intricate control of not only transplacental passage of maternal glucocorticoid to the fetus but also local glucocorticoid action during late pregnancy.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

Specific and transient up-regulation of proprotein convertase 6 at the site of embryo implantation and identification of a unique transcript in mouse uterus during early pregnancy.

The present investigation was conducted to identify and characterize an mRNA that was found by RNA differential display to be uniquely regulated at the sites of embryo implantation in mouse uterus. This mRNA was upregulated at the sites of blastocyst attachment at implantation and was identified as proprotein convertase 6 (PC6). PC6 mRNA level was low in the nonpregnant and early pregnant uterus before embryo implantation commenced (before Day 4.5, vaginal plug = Day 0). During the initiation and progression of blastocyst attachment (around Day 4.5), the mRNA was dramatically upregulated only at the implantation sites. The increased transcription was maintained on Day 5.5; the mRNA level declined slightly on Day 6.5 and then fell sharply to reach the nonpregnant level around Days 8.5-10.5. Thus, the upregulation is transient and coincides with the period of embryo attachment and implantation; it is also very specific to implantation sites. In situ hybridization analysis localized the mRNA expression predominantly in the decidual cells immediately surrounding the implanting embryo at the antimesometrial pole. Additionally, multiple mRNA species resulting from alternative splicing were observed in the uterus, as previously reported in the intestine and brain, and further analysis of these transcripts identified a uterine-specific PC6 mRNA. These data lead us to suggest that PC6 plays an important role in the processes of stromal cell decidualization and embryo implantation.

Animals↗