Estrogen and progesterone receptor isoform distribution through the menstrual cycle in uteri with and without adenomyosis.

Objective: To test the hypothesis that the expression of the different isoforms of the estrogen receptor alpha (ER-α) and beta (ER-β) and the progesterone receptor A (PR-A) and B (PR-B) would be differentially modulated in uteri with adenomyosis compared with controls and that modulation would be related to the menstrual cycle.

Design: Case control, blinded comparison.

Setting: University department.

Phenotypic characterisation of the inner and outer myometrium in normal and adenomyotic uteri.

Background And Aim: To study the characteristics of the inner (IM) and outer (OM) myometrium in the presence and absence of uterine adenomyosis.

Methods: Case control blinded comparison carried out in a university department. Morphometric features of the myometrium were studied in uteri from pre- and postmenopausal women with and without uterine adenomyosis as the sole pathology.

Enhanced invasion of stromal cells from adenomyosis in a three-dimensional coculture model is augmented by the presence of myocytes from affected uteri.

Objective: To compare endometrial stromal cell invasion from women with and without adenomyosis and the effect of myometrial cells using a three-dimensional coculture.

Design: Case-controlled blinded comparison.

Setting: University department.

Spatio-temporal expression patterns of anandamide-binding receptors in rat implantation sites: evidence for a role of the endocannabinoid system during the period of placental development.

Background: Although there is growing evidence that endocannabinoids play a critical role in early pregnancy, there are no studies describing the possible targets for this system after implantation. The endometrial stroma, which undergoes extensive proliferation and differentiation giving rise to the decidua and the trophoblast cells that invade after the initial stages of implantation, are potential targets. Since high anandamide (AEA) levels, the main endocannabinoid, are detrimental to implantation and in order to gain insight into the role of the endocannabinoid system in the development of the fetoplacental unit, the spatio-temporal pattern of expression of the anandamide-binding receptors, CB1, CB2 and the vanilloid receptor (TRPV1), were investigated by quantitative RT-PCR, western blot and immunohistochemistry.

Prevention of tamoxifen induced endometrial polyps using a levonorgestrel releasing intrauterine system long-term follow-up of a randomised control trial.

Objectives: In a RCT, we have previously shown that the levonorgestrel intrauterine system (LNG-IUS, Mirena) produces a decidual response protecting the endometrium at one year follow-up. We here report on the long-term follow-up of this group of women, to test the hypothesis that a LNG-IUS could prevent the pro-proliferative uterine responses of tamoxifen for up to 4.5 years.

The cytoplasmic 60 kDa progesterone receptor isoform predominates in the human amniochorion and placenta at term.

Background: The mechanism that initiates human parturition has been proposed to be 'functional progesterone withdrawal' whereby the 116 kDa B-isoform of the progesterone receptor (PR-B) switches in favour of the 94 kDa A-isoform (PR-A) in reproductive tissues. Recently, other PR isoforms, PR-S, PR-C and PR-M generated from the same gene have been identified and partially characterised.

Methods And Results: Using immunohistochemical, western blotting and RT-PCR techniques, evidence is provided that indicates the major PR isoform present in human term fetal membranes (amnion and chorion) and syncytiotrophoblast of the placenta is neither of the classical nuclear PR-B or PR-A isoforms but is the N-terminally truncated 60 kDa PR-C isoform.

Uterine adenomyosis is associated with ultrastructural features of altered contractility in the inner myometrium.

Objective: To study the ultrastructure of the inner and outer myometrium, in the presence and absence of uterine adenomyosis.

Design: Case control blinded comparison.

Setting: University departments.

Receptor isoforms that mediate estrogen and progestagen action in the female lower urinary tract.

Purpose: Bladder symptoms can be ameliorated by sex steroids but to our knowledge the mechanism of action is unknown. Previous studies of steroid receptor expression in the bladder did not indicate receptor subtype expression. We report the distribution of estrogen and progesterone receptor isoforms in the female lower urinary tract.

Expression of the endocannabinoid system in human first trimester placenta and its role in trophoblast proliferation.

The endocannabinoid, anandamide, which binds to two major receptor proteins, the cannabinoid receptors (CBs) 1 and 2 (CB1 and CB2), has been shown to play a role in first trimester miscarriage possibly through impairment of the developing trophoblast. Although the precise molecular mechanisms underlying this are unknown, plasma anandamide levels are known to be regulated by the progesterone-induced enzyme, fatty acid amide hydrolase (FAAH). Here, we tested the hypothesis that temporal-spatial expression of FAAH, CB1, and CB2 is regulated during early pregnancy and that anandamide detrimentally alters trophoblast proliferation.

Differential regulation of insulin-like growth factor binding protein-1 and -2 by insulin in the baboon (Papio anubis) endometrium.

Background: The purpose of this study was to examine the effect of insulin on expression and synthesis of IGFBP-1 and IGFBP-2 in the baboon endometrium in vitro.

Methods: Baboon endometrial explants collected from cycling, ovariectomized, steroid-treated, simulated-pregnant and pregnant animals were cultured for 48 h in the presence or absence of insulin, with or without estradiol, progesterone and hCG.

Results: Insulin clearly inhibited IGFBP-1 production and mRNA expression in a time- and dose-dependent manner, whereas IGFBP-2 synthesis was not significantly affected.

Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription.

Cannabis use in pregnancy is associated with a range of obstetrical conditions. The molecular mechanisms underlying these effects have not been elucidated but are attributed to the actions of delta-9-tetrahydrocannabinol (Delta9-THC). In this study, concentrations of Delta9-THC equivalent to those found in the serum of cannabis users, i.

Urine protein estimation in hypertensive pregnancy: which thresholds and laboratory assay best predict clinical outcome?

Objective: To determine what threshold for proteinuria could best predict clinical outcome and whether this threshold could be applied universally to any biochemical assay.

Design: A prospective observational study of hypertensive pregnancies referred for further assessment after in a UK University hospital (n=197). Twenty-four hour urine protein was measured by two different assays [benzethonium chloride assay (BCA) and Bradford assay].

The progesterone receptor in human term amniochorion and placenta is isoform C.

The mechanism that initiates human parturition has been proposed to be functional progesterone withdrawal whereby the 116-kDa B isoform of the progesterone receptor (PR-B) switches in favor of the 94-kDa A isoform (PR-A) in reproductive tissues. Recently other PR isoforms, PR-S, PR-C, and PR-M generated from the same gene have been identified and partially characterized. Using immunohistochemical, Western blotting, and RT-PCR techniques, evidence is provided that the major PR isoform present in human term fetal membranes (amnion and chorion) and syncytiotrophoblast of the placenta is neither of the classical nuclear PR-B or PR-A isoforms but is the N terminally truncated 60-kDa PR-C isoform.

Optimal bedside urinalysis for the detection of proteinuria in hypertensive pregnancy: a study of diagnostic accuracy.

Objective: To compare semi-quantitative visual and automated methods of urine testing with fully quantitative point of care urinalysis for the detection of significant proteinuria (0.3 g/24 hours) in pregnancy complicated by hypertension.

Design: A prospective comparative study.

Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction.

Although antenatal infection is thought to play an important role in the pathogenesis of preterm labor and neonatal diseases, the exact mechanisms are largely unknown. We sought to clarify the relationship between antenatal infection and intrauterine and neonatal inflammation. Samples were obtained from 41 preterm infants of <33 wk gestation delivered to 36 mothers and analyzed for the presence of 16s ribosomal RNA (16s rRNA) genes using PCR and for the proinflammatory cytokines IL-6 and IL-8.

Plasma levels of the endocannabinoid anandamide in women--a potential role in pregnancy maintenance and labor?

Although exposure to exocannabinoids (e.g. marijuana) is associated with adverse pregnancy outcome, little is known about the biochemistry, physiology, and consequences of endocannabinoids in human pregnancy.

Immunohistological localization of insulin-like growth factor binding protein-1 in primary implantation sites and trauma-induced deciduomal tissues of the rhesus monkey.

We have earlier demonstrated that there is a close similarity in the temporo-spatial pattern in the onset of oedema, epithelial-plaque transformation, stromal decidualization and influx of granulated lymphocytes in artificially trauma-induced deciduomal endometrium with such events in maternal endometrium at the primary implantation site during early stages of pregnancy in the rhesus monkey. In the present study, we have immunohistochemically examined whether the pattern of insulin-like growth factor-binding protein 1 (IGFBP-1) protein expression in conceptus tissue and maternal endometrium during lacunae and villous placenta stages of gestation in the rhesus monkey is developmental stage-specific and whether a discernible difference exists in the temporo-spatial characteristics of IGFBP-1 protein expression between conceptus associated implantation-decidualization and trauma induced deciduoma in the rhesus monkey. Trophoblast cells failed to exhibit IGFBP-1 immunopositive staining at any stage of implantation-placentation studied.

Mapping of zones of altered morphology and chorionic connective tissue cellular phenotype in human fetal membranes (amniochorion and decidua) overlying the lower uterine pole and cervix before labor at term.

Objective: The purpose of this study was to determine the location, frequency, and extent of altered fetal membrane morphology before term labor and its relation to myofibroblast activation in their connective tissue layers.

Study Design: Fetal membranes that were obtained from 10 women who underwent prelabor cesarean delivery at 38 to 39 weeks of gestation underwent biopsy examination with respect to the internal os of the cervix. The thickness of their constituent layers was measured, and the numbers of alpha-smooth muscle actin immunoreactive cells (ie, marker of myofibroblast activation) within the reticular layer were counted.

3-dimensional colour power angiography for staging human placental development.

Maldevelopment of placental villous trees and their blood vessels results in impaired fetal growth, which can greatly compromise fetal, neonatal, childhood, and adulthood health. There are no means of directly assessing such maldevelopment. We have applied a new technique of imaging (colour power angiography [CPA]) with 3-dimensional reconstruction to assess directly villous development in human pregnancy in vivo in 20 uncomplicated pregnancies from 13 to 38 weeks' gestation.

Validation of the DCA 2000 microalbumin:creatinine ratio urinanalyzer for its use in pregnancy and preeclampsia.

Objective: To determine the accuracy of the DCA 2000 albumin/creatinine ratio urinanalyzer (Bayer Corp., Elkhart, IN) in uncomplicated pregnancy and preeclampsia.

Methods: This was a prospective observational study in a large teaching maternity hospital.

Inhibition of endometrial carcinoma cell growth using antisense estrogen receptor oligodeoxyribonucleotides.

Background: The sex hormone 17 beta-estradiol acts as a mitogen in a number of tissues, including the endometrium, through direct interaction with the estrogen receptor (ER alpha). In the protection of the female breast and endometrium from cancer progression it would be advantageous to inhibit estrogenic action, therefore many estrogen receptor antagonists have been made. However, the most clinically relevant anti-estrogens for breast cancer have a detrimental effect on the endometrium and induce or exacerbate existing endometrial oncogenesis.

Urinary microalbumin/creatinine ratios: reference range in uncomplicated pregnancy.

During uncomplicated pregnancy, the development of proteinuria is accepted as a poor prognostic sign and is associated with increasing maternal and perinatal mortality and morbidity. Physiological proteinuria increases with increasing gestation and one of its largest constituents is albumin. The reference range for the (micro)albumin/creatinine ratio (ACR) has not been described for normal pregnancy.

Endogenous cannabinoids: metabolism and their role in reproduction.

Over the past two decades a number of endogenous compounds that act as ligands for the cannabinoid receptors has been discovered. In analogy with the "endorphins" these compounds have been called "endocannabinoids". Endocannabinoids have been demonstrated in many mammalian tissues including humans and are widely distributed in the CNS, peripheral nerves, uterus, leukocytes, spleen and testicles.

Changes in tenascin-C isoform expression in invasive and preinvasive breast disease.

Tenascin-C (TN) is an extracellular matrix protein that is expressed at low levels in normal adult tissue but is highly expressed around many tumors including breast carcinoma. TN exists as multiple isoforms generated through alternative splicing, and these isoforms have different effects on cell growth and migration. This study has analyzed in detail the pattern of TN isoform expression in benign, preinvasive, and invasive breast lesions using reverse transcription-PCR and Southern blotting.