ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos

ERBB family members and their ligands play an essential role in embryonic heart development and adult heart physiology. Among them, ERBB3 is a binding partner of ERBB2; the ERBB2/3 complex mediates downstream signaling for cell proliferation. ERBB3 has seven consensus binding sites to the p85 regulatory subunit of PI3K, which activates the downstream AKT pathway, leading to the proliferation of various cells. This study generated a human ERBB3 knock-in mouse expressing a mutant ERBB3 whose seven YXXM p85 binding sites were replaced with YXXA. Erbb3 knock-in embryos exhibited lethality between E12.5 to E13.5, and showed a decrease in mesenchymal cell numbers and density in AV cushions. We determined that the proliferation of mesenchymal cells in the atrioventricular (AV) cushion in Erbb3 knock-in mutant embryos was temporarily reduced due to the decrease of AKT and ERK1/2 phosphorylation. Overall, our results suggest that AKT/ERK activation by the ERBB3-dependent PI3K signaling is crucial for AV cushion morphogenesis during embryonic heart development.

Evaluation of yolk sac size and embryonic heart rate in first trimester and pregnancy outcome

Background: Accurate differentiation between normal pregnancy and pregnancy loss in early gestation remains a clinical challenge-previous studies have described the association between embryonic well-beings and the characteristics of gestational sac. The aim of the study was to evaluate the yolk sac size and embryonic heart rate as a prognostic factor for the first trimester pregnancy outcome.Methods: This was a prospective cohort observesional study. It included 52 pregnant women in their first trimester from 6 week till 12 weeks gestation. Transvaginal sonographic examination after explanation and agreement of each patient. All pregnancies were followed for their pregnancy outcome after completion of 12 weeks. The adverse outcome was spontaneous miscarriage occurring before or at 12 weeks of gestation. These patients allocated into four study groups: according to gestational age at presentation and pregnancy outcome. Group I included women who were examined during (6-7 weeks+6 days). Group II included women who were examined during (8-9 weeks+6 days). Group III included women who were examined during (10-12 weeks). Group IV included women who had their pregnancies resulted into first trimester spontaneous miscarriage.Results: The validity of YS diameter regarding the prognosis of first trimester pregnancy outcome shows that; YSD had 100% specificity and 97.8% sensitivity in prediction of miscarriage. Regarding embryonic heartbeat, there was a statistically significant difference between group IV and the other groups. There was embryonic bradycardia in the miscarriage group. EHR had a sensitivity of 97.5% and specificity of 100% in prediction of first trimester pregnancy outcome.Conclusions: Abnormal yolk sac diameter, in the form of small, enlarged, absent or irregular yolk sac, and embryonic bradycardia are associated with poor pregnancy outcome.

Effect of abnormal yolk sac, gestational sac and embryonic heart rate in pregnancy outcome

Background: The purpose of the study is to know the effect of abnormal yolk sac, abnormal gestational sac and abnormal embryonic heart rate on outcome of pregnancy in the tertiary care centre of Chhattisgarh.Methods: This prospective observational study included 50 pregnant females between 6-9 weeks gestation with singleton pregnancy attending antenatal clinic in a tertiary medical institution. Transvaginal sonography was carried out to quantify yolk sac characteristics. Abnormal yolk sac was defined according to Nyberg criteria.Results: Out of 50 cases, 25 cases had abnormal yolk sac, 23 cases had abnormal gestational sac and 22 cases had abnormal embryonic heart rate and heart rate was absent in 23 cases. Out of 50 cases, 32 got aborted and rest 18 cases had ongoing pregnancy beyond 20 weeks. Normal yolk sac diameter (YSD) (2-5 mm) showed 72.2% sensitivity, 62.5% specificity, 52% positive predictive value and 80% negative predictive value in predicting pregnancy outcome. Gestational sac diameter had 66.66% sensitivity, 53.12% specificity, 44.44% PPV and 73.91% NPV and for EHR had 22.22% sensitivity, 96.87% specificity, 80% PPV and 68.88% NPV.Conclusions: The embryos with abnormal YSD are highly associated with poor pregnancy outcome with good sensitivity and NPV. Present study indicates that the yolk sac measurement is reliable prognostic factor in predicting 1st trimester pregnancy outcome.

Does parental heart rate affect embryonic heart rate during incubation? An experiment in Common Terns Sterna hirundo

Embryonic heart rate is a strong determinant of metabolic rate and the rate of embryonic development in oviparous species. In humans, embryonic heart rate is positively correlated with the heart rate of the mother. However, human embryos do not develop autonomously from the maternal circulatory system, making it impossible to separate maternal control from an independent embryonic adjustment of its heart rate to that of its mother. In birds, embryonic development does occur autonomously from the mother, while the embryo can auditively perceive the heart rate of the incubating parent. In this study, we used Common Terns (Sterna hirundo) to experimentally test whether the embryonic heart rate is affected by parental heart rate during incubation. We artificially incubated freshly laid eggs under standardized conditions and continuously exposed them to the sound of either a slow or fast parental heart rate throughout the first 18 days of embryonic development. At day 18 of embryonic development (a few days before hatching) there was no significant difference in the embryonic heart rate between both treatments. There was also no effect of treatment on either total duration of embryonic development or hatching success. We suggest that embryonic heart rate and development rate may not be affected by the heart rate of the parent because natural parental heart rates are very sensitive to external conditions that may fluctuate drastically, while embryos may need a relatively stable heart rate for optimal development.