Interleukin 1 regulates its own receptors in human endometrial cells via distinct mechanisms.

BACKGROUND: Interleukin 1 (IL1) plays an important role in the physiology of human endometrium and is recognized as a major and early embryonic signal. Tight control over the local endometrial action of this cytokine is critical for normal reproductive functions. The coordinated regulation of IL1 receptors types I and II (IL1R1 and IL1R2) and IL1 receptor antagonist (IL1RA) in endometrial cells may represent one of the principle mechanisms involved in the control of IL1 local effects. The objective of this study was to investigate the regulation of IL1Rs in human endometrial epithelial cells in response to IL1. METHODS: Cultures of KLE endometrial epithelial cell line and primary human endometrial epithelial cells, immunofluorescent staining, enzyme-linked immunosorbent assay, western blotting, nuclear transcription (run-on) and real-time PCR were used to investigate the expression of IL1R1, IL1R2 and IL1RA. RESULTS: Cells appeared to react to IL1 by up-regulating the expression of the signaling activating IL1R1 and to moderate in parallel IL1 effects by elevating the expression of the decoy inhibitory IL1R2 and the receptor antagonist IL1RA. Regulation of IL1R1 and IL1RA by IL1B involved gene transcription activation and that of IL1R2 involved mRNA stabilization. CONCLUSION: Considering IL1's immunomodulatory, proangiogenic and tissue remodeling properties, and its role as an embryonic signal, modulation of endometrial cell responsiveness to IL1 via the concomitant regulation of its own activating and inhibitory receptors and receptor antagonist may represent an important regulatory mechanism of IL1-induced physiological changes occurring in the human endometrium during the normal menstrual cycle and embryo development.

Haptoglobin is present in human endometrium and shows elevated levels in the decidua during pregnancy.

Assuming that haptoglobin, by virtue of its immunomodulatory properties, could be a regulatory factor during reproduction, its presence in the human uterus was determined. Protein extracts from endometrial tissue samples of pregnant and non-pregnant women were analysed by the immunoblot technique and the intensities of specific bands were quantified. Bands corresponding to haptoglobin were identified in tissue samples obtained from both sources. Protein, purified by high-performance liquid chromatography and monitored by Western blot analysis for its haptoglobin identity, was used for amino-terminal sequencing. Sequencing of the 42 kDa protein identified it as the beta chain of haptoglobin. Immunohistochemistry was used to corroborate the findings and to visualize the distribution of haptoglobin in the tissue. The intensity of the 42 kDa band derived from decidua graviditatis was significantly higher than the intensity of bands derived from non-pregnant endometrium in the proliferative phase (P < 0.01) and in the secretory phase (P < 0.05). Immunohistochemical staining with anti-human haptoglobin antibody elicited strong signals in the decidua graviditatis and weaker signals in the normal endometrium, with the latter showing menstrual cycle-dependent variation. Moderate staining of stroma and a lack of staining of epithelium in the proliferative phase contrasted with the strong staining of stroma and moderate level of staining of epithelium observed in the secretory phase. Haptoglobin in the uterus may exert several functions such as the known binding of haemoglobin, but could also be involved in the multi-factorial mechanism protecting the fetus from a maternal allograft-like immune response.

Does sweeping of the membranes reduce the need for formal induction of labour? A randomised controlled trial.

OBJECTIVE: 1. To evaluate the effectiveness of sweeping of the membranes to reduce the need for a formal induction of labour; 2. to evaluate the side effects of this intervention. DESIGN: A randomised controlled clinical trial. SETTING: Three tertiary care hospitals of the province of Quebec, Canada. POPULATION: Two hundred women for whom non-urgent induction of labour was medically indicated. METHODS: Women were randomly allocated to sweeping of membranes, or vaginal examination for Bishop scoring only. MAIN OUTCOME MEASURES: 1. Cumulative incidence and relative risk of induction of labour by either oxytocin, prostaglandins or amniotomy; 2. women's discomfort and side effects attributable to sweeping of the membranes. RESULTS: Women allocated to sweeping of the membranes required formal induction of labour less frequently than women in the control group, but this difference was not statistically significant (49% vs 60%, RR 0.83, 95% CI 0.64-1.07). Pain during vaginal examination and other side effects were more frequently reported by women allocated to the sweeping group. CONCLUSIONS: The observed reduction in the need for formal induction of labour is smaller than in previous studies. Side effects and discomfort associated with sweeping of the membranes must be taken into account when counselling women who require induction of labour.

Nature and frequency of chromosomal abnormalities in pregnancies with abnormal ultrasound findings: an analysis of 117 cases with review of the literature.

During a 7-year period, 117 fetal karyotypes were available from 131 genetic amniocenteses. These procedures were performed between 14 and 37 weeks' gestation for the following abnormal ultrasound findings: (1) intrauterine growth retardation (IUGR)--61 cases; (2) fetal malformation--71 cases; and (3) amniotic fluid volume (AFV) abnormality--60 cases. Chromosomal abnormalities were identified in 19 cases (16.2 per cent). Aneuploidy was 2.5 times as frequent in the presence of malformations than in their absence. No correlation was demonstrated between specific fetal malformations and specific chromosomal abnormalities. Aneuploidy was also twice as frequent in the presence of symmetrical IUGR than in its absence. No chromosomal abnormalities were found among eight cases of asymmetrical IUGR. Four cases of aneuploidy presented with isolated IUGR, three of these involving the X chromosome. The frequency of aneuploidy was the same with or without abnormalities of AFV (14.3 versus 16.4 per cent). No chromosomal abnormality was found associated with isolated AFV abnormalities.

Prevention of follicular maturation in endometriosis by subcutaneous infusion of luteinizing hormone-releasing hormone agonist started in the luteal phase.

Six endometriosis patients were treated with continuous subcutaneous (SC) infusion of a luteinizing hormone-releasing hormone (LH-RH) agonist using an external osmotic minipump system. Serum estradiol (E2) was suppressed into the menopausal range within 1 to 2 weeks of treatment started between days 9 and 12 after ovulation. The down-regulation of the pituitary-ovarian axis was maintained for the 24 weeks of treatment. Endometriosis symptoms were relieved during the treatment. At control laparoscopy, implants had regressed markedly and some adhesions had softened, accounting for a significant 58.3% reduction in the mean total American Fertility Society score. Ovulation returned within 14 to 38 days. Four infertile women became pregnant within 2 to 5 months after cessation of treatment. Frequent side effects were hot flushes, and decreased vaginal secretion and libido. There were no significant changes in laboratory blood tests, including cholesterol. The urinary calcium/creatinine ratio increased during the treatment. Thus, starting the treatment in the luteal phase prevented initial follicular stimulation. A better efficacy of treatment would be achieved by the release of an LH-RH agonist at a constant daily rate.