Localization of Cathepsins D and B at the Maternal-Fetal Interface and the Invasiveness of the Trophoblast during the Postimplantation Period in the Mouse

A survey of existing data suggests that trophoblast cells produce factors involved in extracellular matrix degradation. In this study, we correlated the expression of cathepsins D and B in the murine ectoplacental cone with the ultrastructural progress of decidual invasion by trophoblast cells. Both proteases were immunolocalized at implantation sites in lysosome-endosome-like compartments of trophoblast giant cells. Cathepsin D, but not cathepsin B, was also detected ultrastructurally in extracellular compartments surrounded by processes of the invading trophoblast containing extracellular matrix components and endometrial cell debris. The expression of cathepsins D and B by trophoblast cells was confirmed by RT-PCR in ectoplacental cones isolated from implantation chambers at gestation day 7.5. Our data addressed a positive relationship between the expression and presence of cathepsin D at the extracellular compartment of the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period, suggesting a participation of invading trophoblast cells in the cathepsin D release. Such findings indicate that mouse trophoblast cells might exhibit a proteolytic ability to partake in the decidual invasion process at the maternal-fetal interface. Copyright (C) 2010 S. Karger AG, Basel

Deiodinase-mediated thyroid hormone inactivation minimizes thyroid hormone signaling in the early development of fetal skeleton

Thyroid hormone (TH) plays a key role on post-natal bone development and metabolism, while its relevance during fetal bone development is uncertain. To Study this, pregnant once were made hypothyroid and fetuses harvested at embryonic days (E) 12.5, 14.5, 16.5 and 18.5. Despite a marked reduction in fetal tissue concentration of both T4 and T3, bone development, as assessed at the distal epiphyseal growth plate of the femur and vertebra, was largely preserved Lip to E16.5. Only at E18.5, the hypothyroid fetuses exhibited a reduction in femoral type I and type X collagen and osteocalcin mRNA levels, in the length and area of the proliferative and hypertrophic zones, in the number of chondrocytes per proliferative column, and in the number of hypertrophic chondrocyres, in addition to a slight delay in endochondral and intramembranous ossification. This Suggests that LIP to E 16.5, thyroid hormone signaling in bone is kept to a minimum. In fact, measuring the expression level of the activating and inactivating iodothyronine deiodinases (D2 and D3) helped understand how this is achieved. D3 mRNA was readily detected as early as E14.5 and its expression decreased markedly (similar to 10-fold) at E18.5, and even more at 14 days after birth (P14). In contrast. D2 mRNA expression increased significantly by E18.5 and markedly (similar to 2.5-fold) by P14. The reciprocal expression levels of D2 and D3 genes during early bone development along with the absence of a hypothyroidism-induced bone phenotype at this time Suggest that coordinated reciprocal deiodinase expression keeps thyroid hormone signaling in bone to very low levels at this early stage of bone development. (c) 2008 Elsevier Inc. All rights reserved.

Women's experiences of two different self-assessment methods for monitoring fetal movements in full-term pregnancy : a crossover trial

Background: Low maternal awareness of fetal movements is associated with negative birth outcomes. Knowledge regarding pregnant women's compliance with programs of systematic self-assessment of fetal movements is needed. The aim of this study was to investigate women's experiences using two different self-assessment methods for monitoring fetal movements and to determine if the women had a preference for one or the other method. Methods: Data were collected by a crossover trial; 40 healthy women with an uncomplicated full-term pregnancy counted the fetal movements according to a Count-to-ten method and assessed the character of the movements according to the Mindfetalness method. Each self-assessment was observed by a midwife and followed by a questionnaire. A total of 80 self-assessments was performed; 40 with each method. Results: Of the 40 women, only one did not find at least one method suitable. Twenty of the total of 39 reported a preference, 15 for the Mindfetalness method and five for the Count-to-ten method. All 39 said they felt calm, relaxed, mentally present and focused during the observations. Furthermore, the women described the observation of the movements as safe and reassuring and a moment for communication with their unborn baby. Conclusions: In the 80 assessments all but one of the women found one or both methods suitable for self-assessment of fetal movements and they felt comfortable during the assessments. More women preferred the Mindfetalness method compared to the count-to-ten method, than vice versa.

Use of a decision aid for prenatal testing of fetal abnormalities to improve women's informed decision making: a cluster randomised controlled trial [ISRCTN22532458]

Objective To evaluate the effectiveness of a decision aid for prenatal testing of fetal abnormalities compared with a pamphlet in supporting women's decision making.
Design A cluster randomised controlled trial.
Setting Primary health care.
Population Women in early pregnancy consulting a GP.
Methods GPs were randomised to provide women with either a decision aid or a pamphlet. The decision aid was a 24-page booklet designed using the Ottowa Decision Framework. The pamphlet was an existing resource available in the trial setting.
Main outcome measures Validated scales were used to measure the primary outcomes, informed choice and decisional conflict, and the secondary outcomes, anxiety, depression, attitudes to the pregnancy/fetus and acceptability of the resource. Outcomes were measured at 14 weeks of gestation from questionnaires that women completed and returned by post.
Findings Women in the intervention group were more likely to make an informed decision 76% (126/165) than those in the control group 65% (107/165) (adjusted OR 2.08; 95% CI 1.14–3.81). A greater proportion of women in the intervention group 88% (147/167) had a 'good' level of knowledge than those in the control group 72% (123/171) (adjusted OR 3.43; 95% CI 1.79–6.58). Mean (SD) decisional conflict scores were low in both groups, decision aid 1.71 (0.49), pamphlet 1.65 (0.55) (adjusted mean difference 0.10; 95% CI −0.02 to 0.22). There was no strong evidence of differences between the trial arms in the measures of psychological or acceptability outcomes.
Conclusion A tailored prenatal testing decision aid plays an important role in improving women's knowledge of first and second trimester screening tests and assisting them to make decisions about screening and diagnostic tests that are consistent with their values.

Evaluation of a decision aid for prenatal testing of fetal abnormalities : a cluster randomised trial [ISRCTN22532458]

Background: By providing information on the relative merits and potential harms of the options available and a framework to clarify preferences, decision aids can improve knowledge and realistic expectations and decrease decisional conflict in individuals facing decisions between alternative forms of action. Decision-making about prenatal testing for fetal abnormalities is often confusing and difficult for women and the effectiveness of decision aids in this field has not been established. This study aims to test whether a decision aid for prenatal testing of fetal abnormalities, when compared to a pamphlet, improves women's informed decision-making and decreases decisional conflict.

Methods/design: A cluster designed randomised controlled trial is being conducted in Victoria, Australia. Fifty General Practitioners (GPs) have been randomised to one of two arms: providing women with either a decision aid or a pamphlet. The two primary outcomes will be measured by comparing the difference in percentages of women identified as making an informed choice and the difference in mean decisional conflict scores between the two groups. Data will be collected from women using questionnaires at 14 weeks and 24 weeks gestation.

The sample size of 159 women in both arms of the trial has been calculated to detect a difference of 18% (50 to 68%) in informed choice between the two groups. The required numbers have been adjusted to accommodate the cluster design, miscarriage and participant lost – to – follow up.

Baseline characteristics of women will be summarised for both arms of the trial. Similarly, characteristics of GPs will be compared between arms.

Differences in the primary outcomes will be analysed using 'intention-to-treat' principles. Appropriate regression techniques will adjust for the effects of clustering and include covariates to adjust for the stratifying variable and major potential confounding factors.

Discussion: The findings from this trial will make a significant contribution to improving women's experience of prenatal testing and will have application to a variety of maternity care settings. The evaluation of a tailored decision aid will also have implications for pregnancy care providers by identifying whether or not such a resource will support their role in providing prenatal testing information.

Contribution of stretch to the change of activation properties of muscle fibers in the diaphragm at the transition from fetal to neonatal life

The transition from fetal to postnatal life involves clearance of liquid from the lung and airways, and rapid formation of a functional residual capacity. Despite the importance of the diaphragm in this process, the impact of birth on the mechanical and functional activity of its muscle fibers is not known. This study determined the contractile characteristics of individual “skinned” diaphragm fibers from 70 days (0.47) gestation to after birth in sheep. Based on differential sensitivity to the divalent ions calcium (Ca²⁺) and strontium (Sr²⁺), all fibers in the fetal diaphragm were classified as “fast,” whereas fibers from the adult sheep diaphragm exhibited a “hybrid” phenotype where both “fast” and “slow” characteristics were present within each single fiber. Transition to the hybrid phenotype occurred at birth, was evident after only 40 min of spontaneous breathing, and could be induced by simple mechanical stretch of diaphragm fibers from near-term fetuses (∼147 days gestation). Both physical stretch of isolated fibers, and mechanical ventilation of the fetal diaphragm in situ, significantly increased sensitivity to Ca²⁺ and Sr²⁺, maximum force generating capacity, and decreased passive tension in near-term and preterm fetuses; however, only fibers from near-term fetuses showed a complete transition to a “hybrid” activation profile. These findings suggest that stretch associated with the transition from a liquid to air-filled lung at birth induces physical changes of proteins determining the activation and elastic properties of the diaphragm. These changes may allow the diaphragm to meet the increased mechanical demands of breathing immediately after birth.