Coat Protein Mutations That Alter the Flux of Morphogenetic Intermediates through the ϕX174 Early Assembly Pathway.

Two scaffolding proteins orchestrate ϕX174 morphogenesis. The internal scaffolding protein B mediates the formation of pentameric assembly intermediates, whereas the external scaffolding protein D organizes 12 of these intermediates into procapsids. Aromatic amino acid side chains mediate most coat-internal scaffolding protein interactions.

The observer and cycle-to-cycle variability in the measurement of uterine natural killer cells by immunohistochemistry.

The aim of the study was to investigate the various potential sources of variability of counting endometrial uNK cells by immunohistochemistry. Precisely timed endometrial biopsy samples were obtained from women suffering from recurrent miscarriage or recurrent implantation failure (RIF) after IVF on days LH+7-LH+9 of the cycle. uNK cells in wax embedded sections were immunostained for CD56+ and expressed as a percentage of total stromal cells.

The correlation of autoantibodies and uNK cells in women with reproductive failure.

There is conflicting evidence on the role of autoimmune disorders in reproductive failure, including recurrent miscarriage (RM) and recurrent implantation failure (RIF), after in vitro fertilisation (IVF). Several commonly studied autoimmune markers in women with reproductive failure include antiphospholipid antibodies (APAs), thyroid peroxidase antibodies (TPA) and uterine natural killer (uNK) cells. However, there have not been any studies that have examined the correlation of these markers in women with reproductive failure.

Characterization of invasive trophoblasts generated from human embryonic stem cells.

Background: Abnormal human embryo implantation leads to poor foetal development and miscarriage, or pre-eclampsia. Ethical and practical considerations concerning implantation limit its investigation, and it is often difficult to extrapolate findings in laboratory animals when implantation processes show diverse species differences. Therefore, it is important to develop new in vitro models to study the earliest events of human implantation.

Uterine natural killer cells in peri-implantation endometrium from women with repeated implantation failure after IVF.

Several studies have suggested that endometrial uNK (CD56+) cells may play a role in implantation. The aim of this study was to investigate the number of CD56+, CD16+ and CD69+ cells in the unstimulated endometrium of women with recurrent implantation failure after IVF. The percentage of stromal cells positive for CD56, CD16 and CD69 was identified by immunocytochemistry in endometrial biopsies from 15 normal control women and 40 women with recurrent implantation failure.

A preliminary study comparing the endometrial expression of inhibin, activin and follistatin in women with a history of implantation failure after IVF treatment and a control group.

The aim of this study was to evaluate the expression of activin: beta A and beta B subunit and follistatin in endometrium of women with implantation failure (n = 10) and compare it with a fertile control group (n = 7). Immunohistochemical staining intensity for follistatin in the endometrial glandular epithelium from women with implantation failure were significantly lower than that in control women (P = 0.03).

Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage?

Background: Several studies have investigated plasma androgen levels in women with recurrent miscarriage (RM) with conflicting results on whether an association between hyperandrogenaemia and RM exists. However, none of these studies included sensitive androgen measurements using a large data set. We therefore investigated the free androgen index (FAI) in a large number of women with RM in order to ascertain whether hyperandrogenaemia is a predictor of subsequent pregnancy outcome.

Prognostic value of the measurement of uterine natural killer cells in the endometrium of women with recurrent miscarriage.

Background: Studies in mice suggest that CD56 + uterine natural killer (uNK) cells play an important role in implantation. Studies in humans have described an increase in the number of uNK cells in the non-pregnant mid-secretory endometrium of women with unexplained recurrent miscarriage (RM). However, the predictive value of uNK cell number in the maintenance of pregnancy is controversial.

Impact of high body mass index on endometrial morphology and function in the peri-implantation period in women with recurrent miscarriage.

There is evidence that women with a high body mass index may have a higher risk of miscarriage. It is not known if this is due to an endometrial or embryo defect. The aim of this retrospective study was to examine markers of endometrial function in overweight and obese women with recurrent unexplained miscarriage.

Localization and variable expression of G alpha(i2) in human endometrium and Fallopian tubes.

Background: Heterotrimeric G proteins take part in membrane-mediated cell signalling and have a role in hormonal regulation. This study clarifies the expression and localization of the G protein subunit G alpha(i2) in the human endometrium and Fallopian tube and changes in G alpha(i2) expression in human endometrium during the menstrual cycle.

Methods: The expression of G alpha(i2) was identified by Polymerase chain reaction (PCR), and localization confirmed by immunostaining.

A study of luteal phase expression of inhibin, activin, and follistatin subunits in the endometrium of women with recurrent miscarriage.

Objective: To compare the luteal phase endometrial expression of inhibin, activin, and follistatin subunits in women with recurrent miscarriage compared to a control group. Other parameters of luteal function assessed included Doppler blood flow, serum biochemical markers, and histopathology.

Design: This was a prospective case control study.

Menstrual cycle-dependent changes of Toll-like receptors in endometrium.

Background: Rapid innate immune defences against infection usually involve the recognition of invading pathogens by specific pattern recognition receptors recently attributed to the family of Toll-like receptors (TLRs). Reports from our laboratory and others have demonstrated the existence of TLRs 1-6 in the female reproductive tract. However, little has been done to identify TLRs 7-10 in the female reproductive tract, particularly in the uterus.

Expression of integrins in the endometrium of women with recurrent miscarriage.

Immunostaining intensity for alpha(1), alpha(4), alpha(v)beta(3), and beta(3) was assessed by H score in timed peri-implantation endometrium from 21 women with unexplained recurrent miscarriage and 16 healthy fertile women. No significant difference in H scores in gland epithelium, luminal epithelium, stroma, or blood vessels was observed between the two groups, suggesting that alpha(1), alpha(4), alpha(v)beta(3) and beta(3) integrins are expressed normally in the endometrium of women with unexplained recurrent miscarriage.

Cytokine expression in the endometrium of women with implantation failure and recurrent miscarriage.

One potential cause of reproductive failure such as infertility and recurrent miscarriage may be an endometrial defect. Numerous studies in mice have suggested the importance of various different cytokines in successful pregnancy outcome. This article reviews the literature available on the role of T helper cytokines and IL-1, IL-11, LIF, IL-12 and IL-18 in infertility and recurrent miscarriage, with particular emphasis on the role that endometrial cytokines may play.

Inhibin A and activin A may be used to predict pregnancy outcome in women with recurrent miscarriage.

Objective: To look at the role of inhibin and activin in predicting pregnancy outcome in patients with history of recurrent miscarriage.

Design: Observational clinical study.

Setting: Recurrent miscarriage clinic of a tertiary care teaching hospital.

Expression of interleukin-11 receptor alpha and interleukin-11 protein in the endometrium of normal fertile women and women with recurrent miscarriage.

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines. Previous studies have suggested that IL-11 may play a role in human endometrial function. In this study, we have used immunocytochemistry to compare endometrial IL-11Ralpha and IL-11 expression in precisely timed peri-implantation biopsies from 9 normal fertile women and 16 recurrent miscarriage (RM) women.

Markers of endometrial function in women with unexplained recurrent pregnancy loss: a comparison between morphologically normal and retarded endometrium.

Background: Endometrial defect, usually described as luteal phase defect (LPD), is associated with recurrent miscarriage. Recurrent miscarriage has also been associated with the abnormal expression of various molecules by endometrial cells. The aim of this study was to determine if any of these molecules or cells could be used to distinguish LPD from in-phase endometrium.

Expression of leptin receptor isoforms in vitro: lack of effects of leptin on endometrial cytokine and MMP production.

Problem: Leptin has a key role to play in human female reproduction. Its receptor is expressed highly throughout the reproductive tract. Cytokines have an important role in preparing the endometrium for implantation and leptin is known to modulate cytokine production in other tissues.

A review of immune cells and molecules in women with recurrent miscarriage.

Immunological rejection of the fetus due to recognition of paternal antigens by the maternal immune system, resulting in abnormal immune cells and cytokine production, is postulated to be one cause of unexplained pregnancy loss. Although there is evidence for this in rodents, there is less evidence in humans. This article focuses on studies in humans, and reviews the recent literature on the differences in immune cells and molecules in normal fertile women and women with recurrent miscarriage (RM).

Recurrent miscarriage: aetiology, management and prognosis.

Recurrent miscarriage (RM) is a heterogeneous condition. A large number of studies has recently been published, yet many of them have conflicting conclusions. The various aetiological factors, management, prognostic features and outcomes of a subsequent pregnancy in women with RM are reviewed.

Expression of interleukin (IL)-11 receptor by the human endometrium in vivo and effects of IL-11, IL-6 and LIF on the production of MMP and cytokines by human endometrial cells in vitro.

Interleukin (IL)-6, leukaemia inhibitory factor (LIF) and IL-11 belong to the same family of cytokines whose receptors utilize gp130 as the signalling molecule. We have investigated the expression of the IL-11 receptor, IL-11Ralpha, protein in the human endometrium in vivo and the effects of IL-6, LIF and IL-11 on the production of metalloproteinases (MMPs) and cytokines by cultured endometrial epithelial and stromal cells. Immunostaining showed that IL-11Ralpha was expressed in both epithelial and stromal cells, with epithelial staining being more intense than stromal staining and little variation in staining in either compartment throughout the cycle.

Endometrial factors in recurrent miscarriage.

Recurrent pregnancy loss may be a consequence of an abnormal embryonic karyotype, or maternal factors affecting the endometrium resulting in defective implantation. In order to study the endometrial factors responsible for recurrent pregnancy loss, endometrial biopsy samples should be precisely timed according to the LH surge, and the investigation should be carried out in a non-conception cycle, prior to the next pregnancy. The various methods of studying the endometrium including morphological studies, morphometry, immunohistrochemistry, measurement of endometrial protein in plasma and uterine flushings, cytokine expression in endometrial cells, leukocyte populations in the endometrium and ultrasonographic and hysteroscopic studies, were reviewed.

Expression of nuclear factor kappa B components in human endometrium.

Nuclear factor kappa B (NFkappaB) is a family of transcription factors involved in signalling between IL1 and TNFalpha receptors and cytokines and adhesion molecules in a number of cell types, including those of the human endometrium. In this study, we used immunocytochemistry to investigate the in vivo expression of the p50, IkappaBalpha and IkappaBbeta NFkappaB components in endometrium obtained from normal fertile women throughout the menstrual cycle. All three components were expressed by both the stromal and epithelial cells of the endometrium and staining was predominately seen in the cytoplasm of the cells.

Endocrinological and endometrial factors in recurrent miscarriage.

Objective: To investigate the endocrinological and endometrial factors in women with unexplained recurrent miscarriage

Design: Prospective, case study

Setting: Recurrent miscarriage clinic, Jessop Hospital for Women, Sheffield

Participants: One hundred and forty-four women with unexplained recurrent (> or =3) miscarriages

Methods: A blood sample was obtained in early follicular phase (day 3-5) to measure follicle stimulating hormone, luteinising hormone, prolactin, androgens and thyroid function; daily blood/urine samples were obtained from mid-follicular phase to measure luteinising hormone until the luteinising hormone surge was identified; endometrial biopsy and a further blood sample for progesterone measurement were obtained in the mid-luteal phase. A transvaginal ultrasonography was performed to evaluate ovarian morphology.

Results: Hypersecretion of luteinising hormone or ultrasonographic features of polycystic ovarian disease was present in 8% and 7.

Use of human menopausal gonadotropins in the treatment of endometrial defects associated with recurrent miscarriage: preliminary report.

Objective: To test the hypothesis that controlled ovarian stimulation by gonadotropins, which enhances estrogen priming, is of beneficial value in the treatment of endometrial defects associated with recurrent miscarriage.

Design: A retrospective, observational, nonrandomized study.

Setting: A regional recurrent miscarriage clinic in a teaching hospital.