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PubMed1988

Induction of estradiol dehydrogenase activity in human uterine endometrium by synthetic steroids.

The effects of P and six synthetic steroids (MPA, ENT, CAP, R2323, DL and EEL) on estradiol dehydrogenase (E2DH) activity were studied in normal human uterine endometrium in vitro. The mean value of E2DH activity in the proliferative endometrium was 1.5 +/- 0.2 nmol/mg protein/h and that in the secretory endometrium was 10.2 +/- 1.1 nmol/mg protein/h. There was a 7-fold increase in the secretory phase. E2DH activity in the uterine endometrium was stable during the culture period of up to 72 h. In the proliferative endometrium, P, MPA and ENT (approximately 10(-6)M) induced E2DH activity during a 24-h incubation. CAP and R2323 had no significant effect. EEL and DL had negligible effects. In contrast, E2DH activity in the secretory endometrium was not induced further by the steroids. Therefore, in the proliferative endometrium, the elevation of E2DH activity is attributable to the progestational activity and, in the secretory endometrium, E2DH activity is not increased further by the progestational agents because it has been already activated fully by P.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Prolactin production by explants of normal, luteal phase defective, and corrected luteal phase defective late secretory endometrium.

The production of prolactin by explants of late secretory endometrium has been correlated with the extent of decidual differentiation. This correlation is strengthened by the observation that luteal phase defective endometrium produces less prolactin than normal control endometrium in a 24-hour in vitro culture system. In the present study the prolactin production by explants of normal, luteal phase defective, progesterone-corrected luteal phase defective, and clomiphene- or follicle-stimulating hormone/luteinizing hormone-corrected luteal phase defective late secretory endometrium was measured over 96 hours at 24-hour intervals. Progesterone in physiologic concentrations was added to the culture medium to maintain tissue integrity and prolactin synthesis. The prolactin production of normal late secretory endometrium rose over 96 hours under progesterone stimulation. The luteal phase defective endometrium produced significantly less prolactin under the same conditions. Histologically proven corrected luteal phase defective endometrium, regardless of treatment method, produced prolactin not different from the normal controls of the same dates. From these results it is concluded that histologic correction of luteal phase defective endometrium is associated with a corresponding biochemical correction with use of prolactin as a metabolic marker. The findings also strongly support timed endometrial biopsy as the method of diagnosis and evaluation of treatment of luteal phase defect.

Biopsy↗
PubMed1995

Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding--a Nordic multicenter study.

OBJECTIVE: The purpose of this study was to use transvaginal ultrasonographic measurements to find the thickness of the endometrium below which the risk of endometrial abnormality in women with postmenopausal bleeding is low. STUDY DESIGN: This multicenter study was carried out at eight clinics in four Nordic countries. The study included 1168 women with postmenopausal bleeding scheduled for curettage Before the curettage was performed, the thickness of the endometrium was measured with transvaginal ultrasonography. The measurement included both endometrial layers (double-layer technique). The transvaginal ultrasonographic measurement was compared with the histopathologic diagnosis of the curettage specimens. RESULTS: In women with atrophic endometrium the mean endometrial thickness (+/- SD) was 3.9 +/- 2.5 mm. The corresponding figures for women with endometrial cancer were 21.1 +/- 11.8 mm. No malignant endometrium was thinner than 5 mm. In 30 women (2.8%) it was not possible to measure the thickness of the endometrium; one of these women had endometrial cancer. The 95% confidence limit for the probability of excluding endometrial abnormality was 5.5% when the endometrial thickness was < or = 4 mm as measured by transvaginal ultrasonography. CONCLUSION: The risk of finding pathologic endometrium at curettage when the endometrium is < or = 4 mm as measured by transvaginal ultrasonography is 5.5%. Thus in women with postmenopausal bleeding and an endometrium < or = 4 mm it would seem justified to refrain from curettage.

Adult↗
PubMed1983

Uptake of [3H]-arachidonic acid by human endometrium. Differences between normal and menorrhagic tissue.

Human proliferative and secretory endometrium from normal women and from menorrhagic patients was maintained in culture for up to 24 h in the presence of [3H]-arachidonic acid (3H-AA). This prostaglandin (PG) precursor was incorporated into endometrial neutral lipids and phospholipids in a time-dependent manner. Uptake of 3H-AA into phospholipids was significantly higher in normal secretory endometrium than in normal proliferative endometrium. However, this increased uptake of 3H-AA into phospholipids between the 2 phases of the cycle did not occur in menorrhagic endometrium. In contrast, uptake of 3H-AA into neutral lipids (especially triglyceride) was approximately 2-fold higher in menorrhagic endometrium compared to normal endometrium at both stages of the cycle, particularly during the proliferative phase. Abnormalities apparently exist in menorrhagic endometrium in the uptake processes which control arachidonic acid (AA) turnover. These abnormalities may be responsible, in part for abnormal PG production by menorrhagic endometrium.

Arachidonic Acid↗
PubMed1984

Further studies on the control of arachidonic acid turnover in guinea-pig endometrium in relation to prostaglandin production.

The amounts of phospholipids in the guinea-pig endometrium were phosphatidylcholine (PC) greater than phosphatidylethanolamine (PE) = sphingomyelin (Sph.) greater than phosphatidylserine (PS) + phosphatidylinositol (PI). There were no significant differences in the amounts of any of these phospholipids in endometrium between Days 7 and 15 of the cycle. The de novo synthesis of PC was 5- to 10-fold higher than the synthesis of PC from PE in guinea-pig endometrium. There were no differences in the amounts of PC formed by either pathway, and in the amounts of PI synthesized by guinea-pig endometrium between Days 7 and 15 of the cycle during a 6 h culture period. The increased incorporation of arachidonic acid into phospholipids of guinea-pig endometrium on Day 15 compared to Day 7 cannot be accounted for by an increase in phospholipid content or increased phospholipid synthesis on the former day. Following a 24 h labelling period of endometrial lipids with [3H] arachidonic acid (3H-AA), there was a significant decrease in the amount of 3H-AA in PC and PE on Day 15, but not on Day 7, following a further 48 h culture period. Progesterone, oestradiol and A23187 did not affect the amounts of 3H-AA released from the various lipid classes in guinea-pig endometrium during the time periods of culture studied. It is concluded that PC and PE may be the source of arachidonic acid for increased PGF2 alpha synthesis by guinea-pig endometrium after Day 11 of the oestrous cycle. The lack of changes in PI content and PI synthesis between Days 7 and 15 of the cycle indicates that stimulation of the PI cycle is not involved in the biochemical processes which lead to increased AA release and PGF2 alpha synthesis in guinea-pig endometrium after Day 11 of the cycle.

Animals↗
PubMed1986

Metabolism of arachidonic acid and synthesis of prostanoids in human endometrium and decidua.

Arachidonic acid metabolism and prostanoid synthesis were investigated using [14C]-arachidonic acid (AA) in human endometrium obtained at different phases of the ovarian cycle and decidua in early pregnancy. Prostaglandins (PG) identified in endometrium and decidua were PGE2 and PGF2 alpha. The capacity for the production of PGE2 and PGF2 alpha was higher in the secretory phase of endometrium than in the proliferative phase, and the maximum formation of PGE2 and PGF2 alpha was found in the mid secretory phase and in the late secretory phase, respectively. However, the production of PGs was markedly suppressed in decidua. On the other hand, more than 70% of [14C]AA was incorporated into total neutral lipids, whereas less than 22% was incorporated into glycerophospholipids in both endometrium and decidua. Secretory endometrium showed a higher uptake of [14C]AA into glycerophospholipids than did proliferative endometrium, whereas the incorporation into neutral lipids was lower in secretory endometrium than in the proliferative phase. Moreover, decidua showed a similar pattern of incorporation of [14C]AA to the proliferative phase. The changes of arachidonic acid metabolism and PG formation in both endometrium and decidua are discussed in terms of implantation and maintenance of early pregnancy.

Arachidonic Acid↗
PubMed1989

Secretion of the major progesterone-induced proteins of the sheep uterus by caruncular and intercaruncular endometrium of the pregnant ewe from days 20-140 of gestation.

An experiment was performed to evaluate the types and quantity of proteins secreted by intercaruncular endometrium at days 20, 60, 100 and 140 of gestation and caruncular endometrium from days 100 and 140 of gestation. Tissues were obtained from ewes made unilaterally pregnant. Based on SDS polyacrylamide gel electrophoresis (SDS-PAGE), the major proteins present in uterine fluid at days 60-140 of gestation were the uterine milk proteins (UTM-proteins), a pair of structurally-related, progesterone-induced polypeptides with molecular weights of 55,000 and 57,000. These proteins were also present in uterine fluid at day 20, but the major protein at this time migrated coincident with albumin. Cultured explants of endometrium at all days of pregnancy produced UTM-proteins as their major radiolabelled product for both caruncular and intercaruncular endometrium. The amount of protein secretion in vitro was greater (P less than .04) for intercaruncular endometrium than for caruncular endometrium but was not significantly affected by stage of gestation or local presence of the conceptus. Immunohistochemical analysis revealed that UTM-proteins were present in glandular and luminal epithelium of intercaruncular endometrium and in both epithelial and stromal elements of caruncular endometrium. It was concluded that the UTM-proteins are produced earlier than previously described (i.e., day 20). In addition, caruncles contribute to the uterine secretory protein milieu through the secretion of proteins that are similar to that produced by the glandular intercaruncular epithelium.

Animals↗
PubMed2006

Aquaporin-2 expression in human endometrium correlates with serum ovarian steroid hormones.

The aim of the present study was to examine the expression of aquaporin-2 (AQP2), a member of the water channel family aquaporins (AQPs), in human uterine endometrium and its modulation of ovarian steroid hormone at the proliferative and secretory phases. Western blot, immunohistochemistry, and RT-PCR were employed in the present study. Western blot revealed a 29-kDa band that represented AQP2 in human endometrium. The expression of AQP2 in endometrium was confirmed by RT-PCR and immunohistochemical results. The immunohistochemical analysis demonstrated that AQP2 was prominent in luminal and glandular epithelial cells of endometrium. The levels of endometrial AQP2 expression changed during the menstrual cycle and were higher in the secretory endometrium than in the proliferative endometrium. A significantly high level of AQP2 was detected at the mid-secretory phase. There was a positive correlation between the levels of the endometrial AQP2 expression and the concentrations of the serum 17beta-estradiol (E2) or/and progesterone (P4). These data for the first time corroborate that AQP2 is expressed in human endometrium and that the expression of AQP2 in human endometrium might be regulated by E2 or/and P4. The changed expression of AQP2 at different phases of the menstrual cycle may be essential to reproductive physiology in human. The high level of endometrial AQP2 expression was observed at the mid-secretory phase, the time of embryo implantation, suggesting that AQP2 might play physiological roles in the uterine receptivity.

Adult↗
PubMed1999

Changes in prostacyclin synthase in pregnant sheep myometrium, endometrium, and placenta at spontaneous term labor and regulation by estradiol and progesterone.

OBJECTIVE: Our purpose was to investigate, first, whether there were changes in the abundance of prostacyclin synthase protein in intrauterine tissues of pregnant ewes in association with spontaneous term labor. Second, we examined the effect of either estradiol or progesterone, or both, on regulation of prostacyclin synthase protein abundance in uterine tissues using an ovariectomized nonpregnant sheep model. STUDY DESIGN: The abundance of prostacyclin synthase protein was quantified by Western blot analysis in the myometrium, endometrium, and placenta of pregnant ewes in spontaneous term labor (n = 6) and term control ewes not in labor (n = 6). The changes of prostacyclin synthase in the myometrium and endometrium of 20 ovariectomized nonpregnant sheep (n = 5 for each group) were evaluated after treatment with estradiol, progesterone, or both. RESULTS: Prostacyclin synthase protein was present in pregnant and nonpregnant sheep myometrium, endometrium, and placenta at a molecular weight of about 55 kd. At spontaneous term labor the level of prostacyclin synthase decreased in endometrium (P <.05), increased in myometrium (P <.05), and remained unchanged in placenta. Estradiol and progesterone had no effect on prostacyclin synthase protein abundance in nonpregnant ovine endometrium and myometrium. CONCLUSIONS: The decrease in prostacyclin synthase in pregnant sheep endometrium during labor may indicate paracrine interactions between the endometrium, the myometrium, fetal membranes, or a combination of these. The significant increase of prostacyclin synthase in pregnant sheep myometrium at spontaneous term labor may contribute to the increased uterine sensitivity to oxytocin or stimulate vasodilatation during labor to increase myometrial blood flow. Neither estradiol nor progesterone at the dosages studied changed prostacyclin synthase expression in the nonpregnant myometrium and endometrium. The molecular mechanism or mechanisms that differentially regulate prostacyclin synthase expression in pregnant uterine tissues merit further study.

Animals↗
PubMed2001

Interleukin 1beta, interleukin-6, and tumor necrosis factor-alpha in endometriotic tissue and in endometrium.

OBJECTIVE: To compare the levels of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and in endometrium from women with endometriosis and healthy controls. DESIGN: Open. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Twenty-six women with endometriosis and 22 controls operated on for clinical indications. INTERVENTION(S): ELISA in homogenized tissue samples collected during surgery. MAIN OUTCOME MEASURE(S): Levels of IL-1beta, IL-6, and TNFalpha in tissue homogenates. RESULT(S): The three types of tissue differed significantly with respect to all three cytokines. Endometriotic tissue had significantly higher concentrations of IL-1beta than endometrium from both patients with endometriosis and healthy controls. Both endometriotic tissue and endometrium from patients had significantly higher concentrations of IL-6, and endometriotic tissue had significantly lower concentration of TNFalpha than did endometrium from controls. IL-1beta showed a cycle phase dependence that was significant in endometrium from patients, being higher in the secretory than in the follicular phase. IL-1beta was significantly higher in endometrioma than in lesions of other localizations. Concentrations of IL-1beta and IL-6 were positively correlated in endometriotic tissue and in endometrium from controls. No other significant correlations were found. CONCLUSION(S): This study has shown a significant production of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and endometrium, with significant differences between the tissue types, indicating a deviating cytokine pattern in both endometriotic tissue and endometrium from women with endometriosis compared with that from healthy controls.

Endometriosis↗
PubMed1993

In vitro CA-125 secretion by endometrium from women with advanced endometriosis.

OBJECTIVE: To determine if the endometrium of women with endometriosis is a potential source of the elevated serum concentrations of CA-125 associated with endometriosis. DESIGN: Secretion of CA-125 by the endometrium in tissue culture was documented and measured in response to treatment with progesterone (P), 17 beta-estradiol (E2), and progesterone and estradiol (E2+P). Sequential biopsies of the endometrium from the early and late luteal phase were obtained from women with laparoscopically documented normal anatomy or moderate to severe endometriosis. SETTING: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology at the University of Vermont, College of Medicine, Burlington, Vermont. MAIN OUTCOME MEASURES: Secretion of CA-125 by endometrium in vitro was determined by radioimmunoassay in spent media using a commercially available kit (Centicor CA-125 Kit; Centicor, Malvern, PA). RESULTS: Secretion of CA-125 by endometrium in vitro is inhibited by the presence of P and E2+P in both the early and the late luteal phase. The amount of CA-125 secreted increases significantly from the early to the late luteal phase in all treatment groups. When compared with controls, the endometrium of women of with endometriosis secreted two to four times more CA-125 in all treatment groups, in both the early and late luteal phase. CONCLUSIONS: When compared with control endometrium, the endometrium of women with advanced endometriosis secretes significantly more CA-125 and represents a potential source of the elevated serum levels of CA-125 seen in these women.

Adult↗
PubMed1997

Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium.

OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium by ultrasound and to reveal the echogenic difference between the control cycle and the CC cycle. DESIGN: Retrospective study of patients before and during a CC treatment. SETTING: Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. PATIENT(S): Seventy-nine infertile women who had a spontaneous ovulation and a normal luteal function. INTERVENTION(S): Patients received 50 mg/d CC between days 5 and 9 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Endometrial thickness, echogenic pattern of the endometrium, serum E2 content, and E2 and P receptor contents in the endometrium. RESULT(S): Endometrial thickness was significantly thinner during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle, n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic patterns, however, were different between the two cycles on midsecretory days. Moreover, the incidence in which patients showed a grade 3 endometrium on midsecretory days was significantly higher during the conceived CC cycle compared with the not-conceived CC cycle. Serum E2 levels were significantly higher, but E2 receptor contents in the endometrium were significantly lower during the CC cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89 fmol/mg, n = 15) on late proliferative days. CONCLUSION(S): Clomiphene citrate affected the echogenic pattern of the endometrium, and most of the endometrium showed a grade 3 pattern on midsecretory days during the conceived CC cycle. Under the CC treatment, the comfortable endometrium for embryos might be different from the control cycle.

Adult↗
PubMedDate not supplied

Differential expression of interleukins (IL) IL-13 and IL-15 throughout the menstrual cycle in endometrium of normal fertile women and women with recurrent spontaneous abortion.

Interleukins (IL)-13 and IL-15 are novel cytokines and key regulators of immune/inflammatory related responses that are critical in the outcome of various normal biological and associated abnormalities of the endometrium. The present study determined the temporal and spatial expression of IL-13 and IL-15 mRNA and protein in endometrium of normal fertile women throughout the menstrual cycle, and examined whether profiles of their expression differ from endometrium of women with unexplained recurrent spontaneous abortion (RSA). Using quantitative RT-PCR, ELISA and immunohistochemistry we found that IL-13 and IL-15 mRNA and protein are expressed in control endometrium throughout the menstrual cycle and in RSA (cycle days 21-23) with peak expression detected immediately after and prior to onset of menses, and two distinct periods corresponding to late proliferative and the early-mid secretory phases, respectively. The ratio of IL-13:IL-15 expression revealed a predominance in IL-13 expression during late proliferative/early secretory phase and IL-15 during the mid secretory phase. Compared to control endometrium, endometrium of women with RSA expresses elevated levels of IL-13 and IL-15, with IL-13:IL-15 ratio favoring IL-13. The immunoreactive IL-13 and IL-15 were localized primarily in endometrial luminal epithelial cells with an increased intensity in glandular epithelial and stromal cells in RSA. In conclusion, the results indicate that endometrium of normal fertile women expresses IL-13 and IL-15, with a distinct profile during the menstrual cycle and elevated expression in women with RSA. Although the biological significance of IL-13 and IL-15 in human endometrium and their elevated expression in RSA await investigation, these cytokines with distinct biological functions may regulate endometrial inflammatory/immune responses, tissue repair and receptivity for embryo implantation.

Abortion, Habitual↗
PubMedDate not supplied

Granulocyte macrophage colony-stimulating factor in adenomyosis and autologous endometrium.

OBJECTIVE: Granulocyte macrophage colony-stimulating factor (GM-CSF) has been related to macrophage recruitment and activation and has been identified in the human endometrium. We determined whether adenomyosis expresses GM-CSF, and if present, compared GM-CSF protein expression in adenomyosis with that in autologous endometrium. METHODS: We examined ectopic and eutopic endometrium from 16 premenopausal women who had hysterectomies for abnormal uterine bleeding, pelvic pain, or uterine prolapse. Serial sections of premenopausal uteri containing endometrium and adenomyosis were analyzed by immunohistochemistry for GM-CSF ligand and receptor and CD68 macrophages. We analyzed the intensity of staining for GM-CSF ligand and receptor and macrophages in the glandular epithelium and stroma of adenomyosis and autologous endometrium. RESULTS: The GM-CSF ligand localized primarily in the glandular epithelium and myometrium with only light stromal staining. Staining for GM-CSF ligand was significantly higher in adenomyotic glands compared with autologous endometrial glands (P = .002), especially during the secretory phase of the menstrual cycle. There were no statistical differences in the amount and intensity of staining of the GM-CSF receptor in adenomyosis and autologous endometrium. Adenomyotic tissue contained significantly more macrophages than matched autologous endometrium (P = .0004). CONCLUSIONS: Adenomyotic glandular epithelium had greater expression of the GM-CSF ligand compared with autologous endometrium from premenopausal women, which indicates that GM-CSF may play a role in increasing the levels of activated macrophages in women with adenomyosis.

Antigens, CD↗
PubMed1986

[Light and electron microscopy changes in the endometrium caused by the administration of a norgestimate-containing oral contraceptive (Cilest)].

Endometrium morphology has been analysed by means of light microscopy, scanning and transmission microscopy in patients before and during treatment with a norgestimate containing low dose combined pill (Cilest). Endometrium biopsies were taken after 1 (N = 3), 2 (N = 3), 3 (N = 7), 5 (N = 1) and 6 (N = 4) OC cycles. Light microscopy of the endometrium obtained during the OC-free pretreatment cycles shows a regular secretory transformed endometrium. During the first OC cycles of Cilest treatment slight growth retardation of endometrial glands was observed. Endometrium after 3 to 6 OC cycles showed an increasing delay of the growth of endometrial glands in terms of an abortive secretion. Morphometric studies revealed a retardation of the development of endometrial glands and an "arrest of secretion". The degree of proliferation varied slightly; a general delay between the date of the menstrual cycle and endometrial dating was evident. Using scanning electron microscopy the endometrium presented mostly a regular surface corresponding to the midcycle or a late proliferative phase up to the early secretory phase. Infiltrative dysplasia or inflammatory changes as well as local proliferations could not be detected. In transmission electron microscopy with semi-thin and ultrathin slices, stroma, structure of glands and surface appeared to be normal. Furthermore, no time delay between the endometrium and the day of menstrual cycle was observed. During treatment with a norgestimate containing low dose combined pill, only slight changes of the endometrium in terms of a growth retardation of endometrial glands were seen in the first 6 treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraceptives, Oral, Combined↗
PubMed2003

Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane.

BACKGROUND: Not all women with patent tubes develop clinically manifest endometriosis. Quality and quantity of endometrium in retrograde menstruation may be the determining factor in the development of the disease. We hypothesize that retrograde shedding of endometrial fragments with preserved integrity facilitates implantation of endometrium in ectopic locations, resulting in endometriotic lesion development. We evaluate the impact of tissue integrity on the success of endometriosis-like lesion development in the chicken embryo chorioallantoic membrane (CAM) model. METHODS: Menstrual and non-menstrual (cyclic) endometrium were collected by biopsy, and either minced or enzymatically dispersed. Spontaneously shed menstrual effluent was collected by a menstrual cup, and cells and tissue were isolated. We evaluated whether infiltration or lesion formation in the CAM occurred after transplantation of endometrium onto the CAM. RESULTS: Transplantation of biopsied menstrual and cyclic endometrium fragments, and of endometrium fragments >1 mm(3) isolated from menstrual effluent, resulted in lesion formation. Transplantation of endometrial cells isolated from menstrual effluent did not lead to lesion formation. After transplantation of digested biopsied cyclic endometrium, infiltration in the CAM but no lesions were observed. CONCLUSION: In the CAM assay, integrity of tissue architecture determines success of implantation of human endometrium in ectopic locations.

Allantois↗
PubMed2004

Soluble factors from human endometrium promote angiogenesis and regulate the endothelial cell transcriptome.

BACKGROUND: Angiogenesis and vascular remodeling play critical roles in the cyclical growth and regression of endometrium. They also appear to play roles in the pathogenesis of endometriosis. METHODS AND RESULTS: Supernatants were collected from cultured endometrium isolated from women with and without endometriosis. These supernatants induced endothelial cell proliferation and angiogenesis in vitro. They contained vascular endothelial growth factor (VEGF)-A, and their proliferative effects on endothelial cells were partially abrogated by a blocking anti-VEGF-A antibody. Gene array analysis showed that culture supernatants from proliferative phase endometrium, and to a lesser extent secretory phase endometrium, induced significant changes in the transcriptome of endothelial cells. We could not detect any association between endometriosis and the ability of endometrial-derived soluble factors to promote angiogenesis or to regulate the endothelial transcriptome. In addition, we could not detect any association between endometriosis and the concentration of VEGF-A in supernatants from cultured endometrium or in menstrual effluent. CONCLUSIONS: We have shown that endometrium cultured in vitro produced soluble factors, including VEGF-A, that promoted angiogenesis. Proliferative phase endometrium promoted significant endothelial cell transcriptome changes that appear overall to be pro-angiogenic. These transcriptome changes provide insight into the dynamic control of vessel structure on which both eutopic endometrium and endometriotic lesions depend.

Case-Control Studies↗
PubMedDate not supplied

Phenotypic and functional studies of leukocytes in human endometrium and endometriosis.

The aetiology of endometriosis, a common and disabling disorder, is presently unknown, although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity. These studies investigate the relationship between leukocyte populations, steroid hormone receptor expression, proliferative activity, bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle. Significantly increased oestrogen receptor expression, bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis, and CD56+ endometrial granulated lymphocytes (eGLs) were significantly reduced in ectopic endometrium. Apoptotic cells were rarely found in control and subject endometria. In contrast with endometriosis, adenomyotic lesions showed identical steroid hormone receptor expression, proliferative activity, bcl-2 expression and leukocyte subpopulations to eutopic endometrium, indicating different aetiologies for these disorders. The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified (>98%) by immunomagnetic separation. Except for a negligible cytotoxic activity of eGLs from early proliferative samples, cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood, predominantly CD56+ CD16+ natural killer cells. eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses. eGLs are evidently functionally important in the eutopic endometrium. Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis.

Antigens, CD↗