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PubMed1993

Immunohistochemical localization of acidic and basic fibroblast growth factors in normal human endometrium and endometriosis and the detection of their mRNA by polymerase chain reaction.

Growth factors play a role in the cyclical growth and vascularization of normal endometrium. Abnormal endometrial proliferation and neovascularization may result in endometriosis. This study determines the presence and localization of acidic and basic fibroblast growth factors (aFGF and bFGF respectively) in endometrium of normal women, and in normal and ectopic endometrium of women with endometriosis. Endometrium was obtained at curettage or hysterectomy for benign disease, or laparoscopy for endometriosis. aFGF- and bFGF-immunoreactivity was detected at different phases of the menstrual cycle by immunohistochemistry using primary polyclonal rabbit antibodies. Expression of mRNA for aFGF and bFGF was determined in normal endometrium by nested reverse transcriptase polymerase chain reaction (RT-PCR). aFGF- and bFGF-immunoreactivity were both detected in endometrium from normal women, and in normal and ectopic endometrium of women with endometriosis. The pattern of staining with the two different FGFs was the same: immunoreactivity was predominantly confined to glandular epithelial cells and did not change throughout the menstrual cycle. Little or only light staining was seen in stromal cells and myometrium, and the pattern of staining did not differ between endometriotic and normal tissue. The presence of mRNA for aFGF and bFGF was demonstrated in normal endometrium. The detection of aFGF and bFGF mRNA in normal endometrium and aFGF- and bFGF-immunoreactivity in normal and endometriotic tissues suggests that these peptides may play a role in the proliferation and angiogenesis of normal and ectopic human endometrium.

Base Sequence↗
PubMed1993

Thickened endometrium in the postmenopausal woman: sonographic-pathologic correlation.

A correlative sonographic and histopathologic analysis was performed in 35 postmenopausal women with greater than 5-mm thickening of the endometrium at pelvic sonography. Women undergoing estrogen replacement were excluded from study. Four distinct sonographic patterns were encountered. Pattern 1 consisted of echogenic endometrium with small cysts (endometrial polyp with cystic hyperplasia [n = 9], atrophic endometrium with cystically dilated glands [n = 5], and atrophic endometrium [n = 3] at microscopic examination). Pattern 2 was homogeneous echogenic endometrium (proliferative endometrium [n = 3] and adenomyomatous polyp [n = 1]). Pattern 3 was irregular, inhomogeneous endometrium with ill-defined hypoechoic areas (endometrial carcinoma [n = 5], complex hyperplasia with atypia [n = 1], blood clots [n = 1], and atrophic endometrium with eosinophilic metaplasia [n = 1]). Pattern 4 was thin endometrium with fluid in the endometrial cavity (scant atrophic endometrium [n = 6]). Thus, an endometrial thickness of greater than 5 mm in postmenopausal women is associated with a variety of pathologic conditions. Subclassification of sonographic patterns may be helpful in differentiating benign cystic atrophy or cystic endometrial hyperplasia from malignant endometrial lesions.

Aged↗
PubMed1991

Insulin-like growth factor binding proteins in human endometrium: steroid-dependent messenger ribonucleic acid expression and protein synthesis.

The insulin-like growth factor (IGF) autocrine/paracrine system is believed to play a role in endometrial differentiation and trophoblast growth. The IGFs bind with high affinity to a family of binding proteins (IGFBPs) that regulate the actions of the IGFs at their target cells. IGFBP-1, one of three well-characterized IGFBPs in humans, has been shown by numerous investigators to be present in secretory but not proliferative endometrium; however, no information is available with regard to two other human IGFBPs, IGFBP-2 and IGFBP-3, in normal human endometrium. We have examined expression of the messenger RNAs (mRNAs) encoding IGFBP-2 and IGFBP-3 in human proliferative endometrium [under the influence of estradiol (E2)] compared to secretory endometrium (under the influence of E2 and progesterone). Using a complementary DNA probe specific for IGFBP-2, by Northern analysis, expression of a 1.4 kilobase mRNA was found to be differentially expressed in secretory compared to proliferative phase endometrium. Using a complementary DNA probe encoding IGFBP-3, a 2.4 kilobase mRNA was found in endometrium and was also found to be differentially expressed in secretory compared to proliferative phase endometrium. Endometrial stromal cells were established in culture and revealed constitutive synthesis and secretion of IGFBP-2 and IGFBP-3 into the conditioned medium (CM), as detected by Western ligand blot analysis of the CM. Identification of the IGFBPs in the CM was made using IGFBP-2 and IGFBP-3 specific antiserum. In the presence of E2 and progesterone, there was an enhancement in the amount of IGFBP-3 and a marked enhancement of IGFBP-2 in the conditioned media, suggesting sex steroid-dependence of IGFBP-2 and, to a lesser extent, IGFBP-3 protein synthesis. Western ligand blot analysis of IGFBPs in serum throughout the menstrual cycle revealed no hormonal dependence in the serum IGFBPs, suggesting local action of the IGFBPs in endometrium. These data thus show that mRNAs encoding IGFBP-2 and IGFBP-3 are expressed in human endometrium, that their expression is differentially regulated in secretory compared to proliferative phase endometrium (different steroidogenic environments), and that the synthesis of both IGFBP-2 and IGFBP-3 proteins is regulated by steroid hormones.

Autoradiography↗
PubMed1993

Differential expression of messenger ribonucleic acids encoding insulin-like growth factors and their receptors in human uterine endometrium and decidua.

During the menstrual cycle, the endometrium undergoes characteristic changes in response to circulating sex steroids. Intense mitotic activity of glands and stroma occurs in the proliferative (estradiol-dominant) phase, and glandular secretion and stromal differentiation in the secretory (progesterone-dominant) phase. The insulin-like growth factors (IGF-I and IGF-II) promote cellular growth and differentiation and have been proposed to participate in these cyclic endometrial events, acting as mediators of steroid hormones. The objective of this study was to determine whether the messenger RNAs (mRNAs) encoding the IGF peptides and the type I and type II IGF receptors are differentially expressed in human endometrium during the menstrual cycle and in early pregnancy. A solution hybridization ribonuclease protection assay, using 32P-labeled riboprobes for IGF-I, IGF-II, and beta-actin (control), revealed IGF-I gene expression primarily in proliferative and early secretory endometrium and abundant IGF-II gene expression in mid-late secretory endometrium and early pregnancy decidua. Northern analysis, using IGF-I and IGF-II complementary DNA probes, revealed multiple IGF-I mRNAs [2-7.6 kilobase (kb)], expressed primarily in proliferative and early secretory endometrium, and IGF-II mRNAs (1.4-6.0 kb), expressed primarily in secretory endometrium and in early pregnancy decidua. The 7.6-kb IGF-I mRNA and the 6.0-kb IGF-II mRNA were most abundantly expressed. IGF-IEa and IGF-IEb mRNA splicing variants were present in a ratio of about 9:1, respectively. Type I and type II IGF receptor gene expression in endometrium was investigated using specific riboprobes and the ribonuclease protection assay. Messenger RNAs encoding both receptors were more abundantly expressed in the secretory phase and during early pregnancy, compared to the proliferative phase. These results show that mRNAs encoding the IGF peptides and their receptors are differentially expressed in human endometrium, depending on the steroid hormone milieu. The preferential expression of IGF-I mRNA in the proliferative phase supports the hypothesis that IGF-I is an estromedin in human endometrium. The expression of endometrial IGF-II mRNA in the mid to late secretory phase and in early pregnancy supports a role for IGF-II in differentiative functions of the endometrium, perhaps including endometrial tissue shedding in the menstrual cycle or remodeling during early pregnancy.

Base Sequence↗
PubMed2000

Adrenomedullin expression in the human endometrium.

Immunohistochemical studies were performed using a specific antibody to human adrenomedullin (AM) to determine its presence and cellular localization in the human endometrium, in the different phases of the menstrual cycle, and in the postmenopausal period. Specimens were obtained from 21 patients who underwent abdominal hysterectomy for various reasons. The endometrium had no pathological lesion in all cases. In the early and mid proliferative phases of the menstrual cycle, no immunostaining for AM was noted in the endometrium. AM immunostaining in the endometrium became apparent in the late proliferative phase. The staining intensity of AM in the endometrium became more abundant in the secretory phase. No appreciable difference in the staining intensity of AM in the endometrium was noted among early, mid, and late secretory phases. Immunostaining for AM was evident in both the epithelial and stromal compartments of the endometrium. In the postmenopausal endometrium, there was intense immunostaining for AM only in the stromal compartment. This is the first study to demonstrate the expression of AM in the endometrium in relation to the menstrual cycle. The results obtained suggest the participation of AM in the growth and differentiation of the endometrium.

Adrenomedullin↗
PubMed1989

Effect of ovine trophoblast protein-1, oestrogen and progesterone on oxytocin-induced phosphatidylinositol turnover in endometrium of sheep.

In Exp. 1, endometrium was collected from Day-15 cyclic ewes and effects of oTP-1, oxytocin and oTP-1 + oxytocin, in various temporal relationships, on phosphatidylinositol (PI) turnover were determined. Co-treatment of endometrium with oTP-1 and oxytocin inhibited stimulatory effects of oxytocin, while treatment with oTP-1 before and during oxytocin administration had no effect. Turnover of PI was unaffected by oTP-1 alone. In Exp. 2, ovariectomized ewes were treated with progesterone (50 mg/day) for 10 days and then oestrogen (100 micrograms/day) for 2 days and endometrium was collected. Oxytocin stimulated PI turnover in endometrium, but oTP-1 had no effect alone or in combination with oxytocin. In Exp. 3, ovariectomized ewes were treated with corn oil (1 ml/day), oestrogen (50 micrograms/day), progesterone (50 mg/day) or progesterone + oestrogen for 10 days and endometrium was collected. Oxytocin stimulated PI turnover only in ewes that received progesterone. oTP-1 alone had no effect on PI turnover, while co-treatment of endometrium with oxytocin and oTP-1 stimulated PI turnover in ewes treated with progesterone, but not progesterone and oestrogen. Pretreatment of endometrium with oTP-1 stimulated PI turnover when ewes were treated with progesterone or progesterone + oestrogen. Pretreatment of endometrium with oxytocin and then treatment with oTP-1 inhibited PI turnover compared to treatment with oxytocin alone. In Exp. 4, ovariectomized ewes were treated as in Exp. 2. Catheters were placed into the uterine horns and ewes received oTP-1 into one horn and serum into the other twice daily on Days 10-12 of steroid treatment. Endometrium collected on Day 13 was used to measure PI turnover and received either no treatment or oxytocin. Oxytocin stimulated PI turnover in endometrium of these ewes and in-vivo treatment of the ewes with oTP-1 had no effect on PI turnover. These results indicate that antiluteolytic effects of oTP-1 are not mediated by inhibiting effects of oxytocin on phosphatidylinositol turnover if oxytocin receptors are present and that uterine responsiveness to oxytocin is progesterone dependent.

Animals↗
PubMed1985

Human endometrium contains relaxin that is progesterone-dependent.

The avidin-biotin immunoperoxidase method using two anti-porcine relaxin antisera was employed to study the occurrence of relaxin in the endometrium of 102 pre- or postmenopausal women. Relaxin was not found in the endometrium in the following conditions: 1. normal proliferative phase (n = 27), 2. cystic glandular hyperplasia (n = 12), 3. early secretory endometrium during 1-3 postovulatory days (n = 12), 4. atrophic endometrium from postmenopausal women not taking hormones (n = 7), and 5. atrophic or proliferative endometrium of women undergoing estrogen replacement therapy (n = 5). Relaxin was invariably present 1. in the secretory endometrium from natural cycles after day 3 postovulation (n = 28), 2. in the secretory endometrium of previously unovulatory premenopausal women taking progestogens (n = 6), and 3. in the secretory endometrium during the latter part of the cycle of postmenopausal women undergoing estrogen-progestogen replacement therapy (n = 5). Our results indicate that the occurrence of relaxin in the endometrium is progesterone-dependent, but the corpus luteum is not required for relaxin synthesis to occur in non-pregnant women. The timing of the appearance of relaxin in the endometrium during natural cycles coincides with implantation, thus suggesting a role for relaxin in the early events of human reproduction.

Adult↗
PubMed1995

Expression of mRNA for keratinocyte growth factor and its receptor in human endometrium.

BACKGROUND: The aim of the present study was to evaluate the expression of mRNA for the keratinocyte growth factor and the keratinocyte growth factor receptor in human endometrium at different stages of the menstrual cycle. The role of estrogen and progesterone in regulating the expression of the mRNAs encoding keratinocyte growth factor and its receptor was further examined by studying the effect of continuous progestin (endometrium exposed to levonorgestrel releasing intrauterine contraceptive device), and continuous estrogen (endometrium hyperplasia) on the endometrium. METHODS: The expression of mRNA in endometrial samples was evaluated using reverse transcriptase polymerase chain reaction. RESULTS: The expression of KGF mRNA was found to vary during the menstrual cycle, with the highest levels in the progesterone-dominated late-secretory stage endometrium. Keratinocyte growth factor mRNA expression was low in both the endometrium that had been under the influence of continuous progestin (atrophic endometrium) and continuous estrogen (hyperplastic endometrium). The highest level of keratinocyte growth factor receptor mRNA expression was seen in late-proliferative stage of the menstrual cycle and in hyperplasia when the estrogen exposure to endometrium is high. A low receptor mRNA level was found in endometrium exposed to continuous progestin. CONCLUSION: The results suggest that keratinocyte growth factor mRNA expression is progesterone dependent, whereas keratinocyte growth factor receptor mRNA expression seems to be more estrogen than progesterone dependent.

Adult↗
PubMed1998

[The changes of sex steroid receptors and morphology in Norplant treated endometrium].

OBJECTIVE: To study the relationship between the changes of sex steroid receptors as well as endometrial morphology and abnormal uterine bleeding induced by Norplant. METHODS: Immunohistochemistry, Western Blot, in situ hybridization and computer image analysis were employed to demonstrate the expression of estrone receptor(ER) progesterone receptor(PR) protein and mRNA as well as morphometric analysis of the endometrium in Norplant users. RESULTS: The content of DNA and the numbers of spiral arterioles decreased in Norplant treated endometrium. The percentage of glandular area in Norplant endometrium was much lower than that in cyclic endometrium. A statistically significant correlation was observed between the percentage of area of glands and abnormal uterine bleeding, as well as serum estrogen(E2) level, but E2 level had no direct relationship with the bleeding abnormality. As the time growing, the percentage of glandular area increased. Immunostaining and relative concentration of glandular and stromal ER in Norplant treated endometrium were significantly weaker and less than all the stage of cyclic endometrium. However, PR, especially stromal PR immunostaining was very intense, which was the same or more than that in all the stage of cyclic endometrium. In situ hybridization detected that the ER and PR mRNA was lower in Norplant treated endometrium than that in cyclic endometrium. The ER mRNA expression was more less abundant than PR mRNA expression. CONCLUSION: These results suggested that poor repair and regeneration of endometrium(especially glands and spiral arterioles) and abnormal expression of ER and PR may be related to pathogenesis of abnormal uterine bleeding induced by Norplant implant.

Adult↗
PubMedDate not supplied

[Transvaginal sonography of the postmenopausal endometrium].

INTRODUCTION: The most frequent symptom suggesting endometrial pathology is uterine bleeding. Each postmenopausal uterine bleeding requires fraction explorative curettage and histopathologic examination of the material obtained from the cervical canal and uterine cavity. The aim of this study was to estimate the efficacy of ultrasonography as a non-invasive method in detection of endometrial pathology in postmenopausal women, and to find out whether its more frequent use could safely decrease the number of curettages in detection of these conditions. MATERIAL AND METHODS: A prospective investigation has been performed in postmenopausal women not menstruating for more than a year, and who reported to the Department of Obstetrics and Gynaecology in Novi Sad for uterine bleeding during 1996 and 1997. Each woman underwent ultrasonographic examination by vaginal probe of 5 MHz and fraction curettage, whereas the samples from cervical canal (if obtained) and from uterine cavity were sent to histopathologic examination to the Institute of Pathology in Novi Sad. Standard statistical methods have been used for the analysis of the results. Validity of the applied ultrasonographic method in detecting endometrial pathology has been estimated by calculation of its sensitivity and specificity. RESULTS: A satisfactory visualisation of the endometrium has been obtained in all 35 examined cases. The thinnest endometrium was 1 mm wide and the thickest one was--25 mm. The fraction curettage has been used to obtain material from the cervix in 2 cases and from the uterine cavity in 35 cases. In our patients with uterine bleeding, who were in the postmenopause for 13 years on average, endometrial atrophy was recorded in 17.14%, endometrial polyp in 11.43%, endometrial hyperplasia in 22.86%, endometrial adenocarcinoma in 42.86% and uterine sarcoma in 5.71%. There were 2 false negative ultrasonographic findings (2 cases of endometrial hyperplasia) and sonographic thickness less than standard versus 2 false positive cases (endometrium thicker than the limit value, 7 and 14 mm, with no real pathology) which showed that the sensitivity of the investigated method was 93.10% and the specificity was 66.66%, if the limit value for the thickness of endometrium was 3 mm. DISCUSSION: Ultrasonographic thickness of endometrium means maximum double thickness in longitudinal plane, i.e. the distance of the opposite bordering surfaces of endometrium and myometrium. The procedure of measurements of endometrial thickness is simple in most cases. Most authors agree that there is a positive correlation between the thickness of endometrium and its pathological conditions. The most often used limit values are 3 and 4 mm. Higher limit values of endometrial thickness increase the sensitivity of the method even to 100%, but negatively affect its specificity making this method inadequate as a screening method for endometrial carcinoma. Many authors insist on introducing other criteria for evaluation of the endometrium i.e. for taking its thickness as the only criterion. Ultrasonography does not provide a completely safe differentiation between benign hyperplasia and endometrial carcinoma. CONCLUSION: The transvaginal sonography is an efficient and acceptable, noninvasive method for early detection of endometrial pathology in postmenopausal women. The thickened endometrium during menopause is the most significant ultrasonographic criterion implicating its pathology. The vaginosonographically measured thickness of 3 mm and less, gives a relatively safe prediction of endometrial atrophy, whereas the thickness above 3 mm requires explorative curettage and histopathologic examination of the endometrium, no matter if the woman has or has not uterine bleeding. (ABSTRACT TRUNCATED)

Aged↗
PubMed2001

[Study on the distribution of lymphocyte subsets in the eutopic and ectopic endometrium of women with endometriosis].

OBJECTIVE: To investigate the abnormal distribution of lymphocytes in eutopic and ectopic endometrium of patients with endometriosis and its significance. METHODS: In 43 cases, biopsies of ectopic tissues were taken by laparoscopy and laparotomy from patients with endometriosis and eutopic endometrium by curettage at the same time. In 19 cases, eutopic endometrium was taken from hysterectomy for myomatous uterus. Immunohistochemical techniques were employed to demonstrate the difference in the number and ratio of the lymphocyte subsets between the patients with endometriosis and the controls. RESULTS: In the patients with endometriosis, in the proliferative phase, ectopic endometrium contained respectively CD3+ CD8+ T cells and CD68+ macrophages (67.2 +/- 13.5)/5 HP, (45.0 +/- 14.0)/5 HP and (37.2 +/- 10.6)/5 HP, significantly higher then that in the eutopic endometrium (52.4 +/- 11.3)/5 HP (P < 0.01), (32.5 +/- 10.0)/5 HP (P < 0.05), and (30.7 +/- 10.3)/5 HP, and also higher as compared with the control group (52.1 +/- 14.9)/5 HP (P < 0.05), (28.9 +/- 12.7)/5 HP (P < 0.01), (26.3 +/- 9.3)/5 HP (P < 0.05); in the secretory phade, CD8+/CD4+, and CD68+ content was respectively 3.5 +/- 1.2, (40.3 +/- 12.2)/5 HP, higher than that in the control group, 3.2 +/- 0.8 (P < 0.05), (28.6 +/- 10.6)/5 HP (P < 0.01). The number of macrophages was also significantly increased. No cyclic changes in the number of lymphocytes in each subpopulation in ectopic endometrium were found. CONCLUSIONS: In the patients with endometriosis, the changes in T lymphocytes and macrophages are mainly on the endometriotic sites. The infiltration of many lymphocytes and macrophages into the ectopic endometrium formed a chronic inflammatory process. The lymphocytes are not able to clear the ectopic endometrium in the late stages of endometrium, on the contrary, they stimulate the further growth of the endometrium.

Adult↗
PubMed1994

Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors.

The insulin-like growth factor (IGF) system is thought to function as a mediator of steroid hormone actions in the endometrium. IGFs (IGF-I and IGF-II) are also potent mitogens in endometrial cancer. The biological actions of IGFs are modulated by specific binding proteins (IGFBP)--6 cloned and sequenced so far--which may either inhibit or enhance the effects of IGF at the cellular level. In the endometrium, IGFBP-1 gene expression is stimulated by progesterone and inhibited by insulin, while IGFBP-1 inhibits the mitogenic action of IGF-I. In this study, we used a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to investigate IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 and IGFBP-6 gene expression in endometrial cancer tissues. Endometrial cancer tissue samples were collected from 20 women (aged 54-79 yrs) with stage I to II well-differentiated endometrial adenocarcinoma. Samples of normal endometrium (n = 14) obtained from women undergoing tubal ligation in various phases of the menstrual cycle, and normal early-pregnancy endometrium (decidua) were studied for comparison. In endometrial cancer tissues, the IGFBP-1 mRNA was undetectable or minimally expressed when studied by RT-PCR. The mean (+ SD) levels of IGFBP-2 and IGFBP-4 and IGFBP-5 mRNAs in endometrial cancer tissues did not differ from those in normal endometrium, in which no cyclic variation was observed, suggesting that the genes encoding IGFBP-2, IGFBP-4 and IGFBP-5 are not hormonally regulated in the endometrium. The IGFBP-6 mRNA expression showed a significant cyclic variation in normal endometrium, with low levels in late-proliferative and early- to mid-secretory phases and high expression in late-secretory and early-proliferative phases. In endometrial cancer tissues, the mean IGFBP-6 mRNA level was similar to that in cycling endometrium during the peri-ovulatory period. In summary, a continuous stimulation of the endometrial epithelial cells by IGFs with suppressed IGFBP-1 expression may lead to an imbalance in the IGF system of the endometrium and trigger an uncontrolled cell proliferation, ultimately resulting in malignant transformation.

Adenocarcinoma↗
PubMed1995

Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis).

OBJECTIVE: The Sampson hypothesis of retrograde menstruation as a cause of endometriosis was tested by determining the effect of intrapelvic injection of menstrual versus luteal endometrium on the incidence, peritoneal involvement, and stage of endometriosis. STUDY DESIGN: Seventeen baboons were injected retroperitoneally with luteal (n = 6) or menstrual (n = 7) endometrium and intraperitoneally with menstrual endometrium (n = 4). Laparoscopies were performed after 2 months in all animals and after 5 and 12 months in six and five primates injected with luteal and menstrual endometrium, respectively. RESULTS: The peritoneal endometriosis surface area, number of implants, and incidence of typical and red subtle lesions were significantly higher after retroperitoneal injection of menstrual than of luteal endometrium. By use of menstrual endometrium intraperitoneal seeding was more successful in causing endometriosis than was retroperitoneal injection. No significant changes in number or surface area of endometriotic lesions induced with retroperitoneal injection of luteal endometrium after 5 months were observed in the six baboons. At repeat laparoscopy 12 months after intrapelvic injection of menstrual endometrium progression was recorded in three of four regularly cycling animals, whereas regression was evident in one baboon that had become amenorrheic after induction. CONCLUSION: Intrapelvic injection of menstrual endometrium can cause peritoneal endometriosis and offers experimental evidence supporting the Sampson hypothesis.

Animals↗
PubMed1991

Effect of porcine conceptus secretory proteins on in vitro secretion of prostaglandins-F2 alpha and -E2 from luminal and myometrial surfaces of endometrium from cyclic and pseudopregnant gilts.

Uterine endometrium collected from pseudopregnant (PP) and cyclic gilts on day (D) 15 after estrus were perifused in vitro with 10 ug/ml of porcine conceptus secretory proteins (pCSP) or serum proteins (SP) in Krebs ringer bicarbonate (KRB) buffer. In Experiment 1, samples were collected from luminal and myometrial surfaces of endometrium and concentrations of prostaglandin F2 alpha (PGF) determined by radioimmunoassay (RIA). Secretion of PGF by endometrium from cyclic gilts was stimulated (P less than .05) by pCSP. In Experiment 2, endometrium from D 14 cyclic and PP gilts was perifused and concentrations of PGF and prostaglandin E2 (PGE) in perfusate were determined by RIA. Across both statuses, luminal surface secretion of PGF was stimulated (P less than .05) by pCSP. Treatment with pCSP decreased secretion of PGE from myometrial surface of endometrium from cyclic gilts and increased (P less than .01) secretion of PGE from the myometrial surface of endometrium from PP gilts. In Experiment 3, pCSP were separated into acidic and basic fractions by anion exchange chromatography and each fraction was perifused separately over the luminal surface of endometrium from cyclic and PP gilts. Perifusion with acidic pCSP suppressed secretion of PGF by endometrium from cyclic or PP gilts; while basic pCSP did not influence secretion of PGF. These results demonstrated that products secreted by Day 15 pig conceptuses stimulate release of PGF and PGE from porcine uterine endometrium.

Animals↗
PubMed2006

Interleukin-18 system messenger RNA and protein expression in human endometrium during the menstrual cycle.

OBJECTIVE: To investigate the IL-18 system, including IL-18, IL-18 receptor (IL-18R), IL-18 binding protein (IL-18BP), and IL-18 precursor (proIL-18), mRNA and protein expression in human endometrium during the menstrual cycle. DESIGN: Controlled study. SETTING: Clinical and academic research setting in a university medical center. PATIENT(S): Human endometrium was obtained from surgical specimens of normal cycling women undergoing hysterectomy for benign reasons. INTERVENTION(S): A total of 24 human endometrium samples were obtained at proliferative and secretory phase from surgical specimens of normal cycling women undergoing hysterectomy. Quantitative competitive polymerase chain reaction (QC PCR) and immunohistochemistry were performed. MAIN OUTCOME MEASURE(S): The differences of IL-18 system mRNA and the ratio of antagonist to agonist in both proliferative and secretory phases of endometrium were analyzed. RESULT(S): Our results showed a complete IL-18 system, including mRNA expression and protein production in both proliferative and secretory phases of the endometrium. The QC PCR demonstrated that both IL-18 and IL-18R decreased and IL-18BP increased mRNA expression in human endometrium in secretory phase compared with proliferative phase. A positive correlation of IL-18 and IL-18R in human endometrium was demonstrated in proliferative phase but not in secretory phase. In addition, there is a significantly higher ratio of IL-18BP to IL-18 mRNA levels in secretory endometrium compared with proliferative phase endometrium (P<.05). CONCLUSION(S): The expression and ratio of IL-18 antagonist to agonist may be responsible for embryo implantation.

Endometrium↗
PubMed1984

Placental protein 12 (PP12) is induced in the endometrium by progesterone.

The occurrence of PP12 was studied by the biotin-avidin immunoperoxidase method in the endometrium of 106 premenopausal and postmenopausal women at various phases of the menstrual cycle or during estrogen and progestogen replacement therapy. No PP12 was found in the endometrium under the following conditions: (1) during the proliferative phase, (2) in cystic glandular hyperplasia, (3) during the first 3 postovulatory days in ovulatory cycles, (4) in atrophic postmenopausal endometrium, and (5) in estrogen-stimulated postmenopausal endometrium. PP12 was found in the endometrium under the following conditions: (1) in the secretory endometrium from the fourth postovulatory day onward, (2) in the endometrium during progestogen treatment of previously anovulatory premenopausal women, and (3) in the endometrium from postmenopausal women treated with estrogen followed by combined estrogen and progestogen replacement therapy. These results suggest that PP12 is a P-dependent protein which, in natural cycles, appears in the endometrium around the time of implantation and, in postmenopausal women, can be induced by progestogens after estrogen priming.

Endometrium↗
PubMed1995

Plasminogen activators in ectopic and uterine endometrium.

OBJECTIVE: To investigate the expression of the plasminogen activator (PA)-plasmin system components in ectopic endometrium and in uterine endometrium from women with and without endometriosis. DESIGN: Plasminogen, PAs (urokinase and tissue plasminogen activator), and PA inhibitors (1 and 2) were detected by immunohistochemistry using a alkaline phosphatase staining method. RESULTS: No differences in staining were found between uterine endometrium of women with endometriosis and women without endometriosis with any of the antibodies used. However, we did find differences between uterine and ectopic endometrium. Although the expression of the components of the PA-plasmin system reflected the cyclic changes in the hormonal levels in uterine endometrium, ectopic endometrium maintained a very high level of plasminogen and urokinase in every sample. We were unable to detect the presence of PA inhibitors in either uterine or ectopic endometrium. CONCLUSIONS: There is no evidence that uterine endometrium from women with endometriosis is originally more able to implant than that of women without the disease because of an increase in their PA expression. The high levels of urokinase and plasminogen in ectopic endometrium may reflect a more invasive nature of the endometriotic implants in the peritoneal cavity.

Endometriosis↗
PubMed1999

Involvement of ovarian steroids in basal and oxytocin-stimulated prostaglandin (PG) F2 alpha secretion by the bovine endometrium in vitro.

It is assumed that exposure of endometrium to spontaneously secreted luteal hormones stimulates PGF2 alpha secretion and modifies oxytocin (OT) influence on the bovine uterus. At first, the time-dependent effect of endogenous luteal products on endometrial PGF2 alpha secretion was examined. Endometrial strips (100 mg) from slaughtered heifers (Days 11 to 17 of the cycle) were incubated alone or with luteal cells (1 x 10(5) cells/mL). The highest PGF2 alpha secretion by the endometrium under influence of hormones secreted from luteal cells was observed after 12 h of incubation compared with the control (P < 0.001). Then, endometrium (Days 11 to 17) was incubated with luteal cells and concomitantly with antagonists of P4 and OT. The P4 antagonist prevented the stimulatory effect of endogenous luteal hormones on PGF2 alpha secretion (P < 0.05), but the OT antagonist did not. Further, direct effects of exogenous P4, OT and estradiol (E2) on endometrial PGF2 alpha secretion (Days 11 to 17) were examined. Both OT and P4 increased PGF2 alpha secretion (P < 0.05); E2 alone had no effect on PGF2 alpha secretion, but it amplified the P4 effect (P < 0.05). Finally, we studied the effect of endogenous luteal products on OT-stimulated PGF2 alpha secretion from endometrium. When endometrium (Days 11 to 17) was incubated without luteal cells, OT stimulated PGF2 alpha secretion (P < 0.001), whereas incubation of endometrium with luteal cells abolished the stimulatory effect of OT on PGF2 alpha secretion (P < 0.001). These treatments did not affect PGF2 alpha secretion from the endometrium collected on Days 1 to 4. In conclusion, P4 stimulates PGF2 alpha secretion by the endometrium and E2 amplifies this effect. As long as the endometrium is under the influence of P4, ovarian OT does not affect PGF2 alpha secretion.

Animals↗