Diffusion tensor imaging determines three-dimensional architecture of human cervix: a cross-sectional study.

OBJECTIVE: To determine the microarchitecture of the cervix using high-resolution diffusion tensor (DT) magnetic resonance imaging (MRI). DESIGN: Cross-sectional study. SETTING: Leeds, UK. SAMPLE: Women undergoing hysterectomy for benign pathology. METHODS: Ex-vivo DT-MRI measurements were obtained using a 9.4-T Bruker nuclear magnetic resonance (NMR) spectrometer on seven fixed human cervices obtained at hysterectomy. A deterministic fibre-tracking algorithm was used to indirectly visualise underlying fibre organisation. Inter-regional differences in tissue structure were sought using quantitative measurements of diffusion. MAIN OUTCOME MEASURE: The identification of an occlusive structure in the region corresponding to the internal cervical os. RESULTS: Fibre tracking demonstrated two regions: an outer circular and inner longitudinal layer. The total circumferential tract volume (TV) was greatest in the proximal region of the cervix (TV: proximal, 271 ± 198 mm3 ; middle, 186 ± 119 mm3 ; distal, 38 ± 36 mm3 ). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measurements were significantly different between regions in all samples (P < 0.0005), indicating greater tract density and organisation towards the internal os. CONCLUSION: Fibre tracking infers a system of dense, well-defined, encircling fibres in the proximal region of the cervix, corresponding to the location of the internal os. These findings may provide evidence of specific anatomic microarchitecture within the cervix able to resist intrauterine forces associated with pregnancy. TWEETABLE ABSTRACT: Diffusion-tensor MRI derived tractography identified well-defined encircling fibres at the internal os.

Interrelationship of cytokines, hypothalamic-pituitary-adrenal axis hormones, and psychosocial variables in the prediction of preterm birth.

BACKGROUND/AIMS: To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. METHODS: In this prospective case-control study, maternal serum biomarkers were quantified at 9-23 weeks' gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. RESULTS: Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-alpha were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743-0.874). CONCLUSION: Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator.

Dynamic regulation of alpha-dystroglycan in mouse placenta.

Alpha dystroglycan (alpha-DG) is a peripheral membrane protein important in cellular interaction with other cells and the extracellular matrix. Recent data suggests that the Dag1 gene, which encodes alpha-DG, is important for implantation. In addition to its importance in cellular function, alpha-DG also serves as a cellular receptor for members of the arenaviridae family of viruses, which can cause placental infection. Because of its apparent dual role in implantation and its role as a viral receptor, we sought to determine placental and uterine alpha-DG expression during mouse pregnancy. Dag1 is expressed throughout gestation in the placenta and to a lesser extent in the uterus, with the highest levels in early gestation. By Western blot analysis, the glycosylated protein is also expressed and the pattern of glycosylation changes to favor the most highly glycosylated forms at mid gestation. These data support the idea that alpha-DG may be a target for evolutionary host-pathogen interactions at the maternal-fetal interface.

Hepatitis C virus (HCV): prevalence in a gynecological urgent care clinic population.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) among women seeking urgent gynecological care. METHODS: Women were asked to complete a short self-assessment screening of HCV risk. Those answering yes to any of the screening questions were offered HCV testing and were asked to complete a more detailed questionnaire. RESULTS: Among the 125 women who completed the screening questionnaire, 80% (100) answered yes to one or more of the screening questions. Of the 99 women who underwent testing, six (6.1%) were HCV seropositive; a history of injection drug use was the only finding associated with HCV seropositivity (R.R 9.7: 95% CI 1.90-49.40). CONCLUSIONS: Women seeking urgent outpatient gynecological care, particularly those who are injection drug users, are at a substantial risk of HCV infection. A careful risk assessment should be completed in order to identify women who should be offered HCV testing.

The H-Y response in mid-gestation and long after delivery in mice primed before pregnancy.

The mechanisms underlying maternal tolerance of the semi-allogeneic fetus are not completely understood. The maternal immune system's response to the male antigen, H-Y is an example of the conflicting evidence that both supports and refutes the idea that the immune system in pregnant females is fundamentally different from that in non-pregnant females. Although multiple pregnancies may inactivate H-Y specific T cells, the immune system of the pregnant female can also generate a cytotoxic response to this antigen. To help understand this apparent conflict, we immunized female mice against H-Y with male spleen cells before pregnancy and examined the subsequent anti H-Y response during mid-pregnancy. The pregnant mice studied were able to mount cytotoxic immune responses to H-Y that were equivalent to those generated in their non-pregnant counterparts. Moreover the experience of pregnancy did not impair the ability to maintain immunologic memory to H-Y. The data support the idea that pregnancy does not violate general rules of antigen specific immunity, even if the antigen is expressed on the fetus.

Maternal tolerance is not critically dependent on interleukin-4.

Pregnant animals can generate and maintain immune responses to fetal antigens. This however, does not usually lead to fetal loss. At least two types of immune response are recognized. T helper type 1 (Th1) responses support the generation of cellular cytotoxicity. In contrast, Th2-type responses support the production of non-cytotoxic antibody and suppress the Th1-type. One attempt to explain why the fetus is not generally rejected has been to suggest that during pregnancy Th2-type responses are dominant. These responses rely heavily on interleukin-4 (IL-4) for both functions. This work focuses on maternal immunity to the male antigen H-Y, which is expressed in male fetuses. When injected with male spleen cells, female mice of certain strains mount a cytotoxic immune response to H-Y. However, pregnant females immunized in this way do not deliver litters with fewer males. To help delineate the possible role of IL-4 in such maternal tolerance, female mice genetically deficient in IL-4 were studied. The results show that: (1) deficiency in maternal IL-4 does not affect fertility, (2) deficiency in IL-4 is not associated with selective loss of male offspring in unimmunized mice, (3) pregnancy does not obliterate anti-H-Y reactivity in immunized mice and (4) maternal immunity to H-Y in the absence of IL-4 does not result in loss of male offspring. The results suggest that IL-4-dependent Th2-type responses are not critical to maternal tolerance. Other cytokines must be examined for their role in this phenomenon.

Gamma-delta T cells in midgestation human placental villi.

One question that remains is how the immune system at the maternal-fetal interface supports tolerance of the fetus while at the same time protecting it from infection. A potential answer is that local innate immunity is augmented while adaptive immunity is downregulated. In this study, we focus on T cells of the gamma-delta lineage, thought to be important in certain innate responses. Using tissue from normal pregnancies, we documented the presence of gamma-delta T cells and their counterpart, alpha-beta T cells, in midgestation human placental villi. The variable presence of these two T cell lineages in this anatomic site may suggest differential regulation, and herein we describe potential mechanisms for this phenomenon.

The maternal immune system's interaction with circulating fetal cells.

Although female mice readily reject organs from allogeneic or semiallogeneic male donors, they do not reject the fetuses sired by those same donors. An explanation for this that has been made in the past is that the fetus influences its mother's immune response by sending fetal cells into the maternal circulation. To determine the frequency and magnitude of fetal to maternal cell migration, we employed a sensitive quantitative PCR technique to assess the numbers of male cells in the thymus, spleen, liver, lymph nodes, and peripheral blood of normal mice undergoing their first pregnancy. We found that fetal cell migration is not universal but occurs in only a fraction of pregnancies. Using a kinetic analysis of normal mice mated to syngeneic or allogeneic males, a comparison of normal and SCID mice, and testing of multiparous mice for CTL against fetal Ags, we found that migrating fetal cells were cleared by the maternal immune system. Thus the mother is not continuously exposed to circulating fetal cells and, in fact, has the capacity to eliminate them without eliminating the fetus.