Cyclical and Patch-Like GDNF Distribution along the Basal Surface of Sertoli Cells in Mouse and Hamster Testes

BACKGROUND AND AIMS: In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs) through GDNF family receptor α1 (GFRα1). It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules

Preterm toddlers have low nighttime sleep quality and high daytime activity.

A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers’ waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development

Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction

Objective: To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR).Methods: Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. Results: Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25–72.8) was associated with adverse maternal and neonatal outcomes. Conclusion: A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR

Predictive value of the sFlt-1/PlGF ratio for preeclampsia in twin pregnancies: a retrospective study

Objective: This study aimed to investigate the efficiency of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in predicting preeclampsia (PE) within 4 weeks in twin pregnancies. Methods: Seventy-eight women with serum angiogenic markers measured at 28 + 0 to 30 + 6 weeks of gestation were enrolled. A receiver-operating characteristic curve was used to determine the sFlt-1/PlGF ratio threshold to predict PE. Results: A cutoff value for the sFlt-1/PlGF ratio of 22.2 predicted PE presence within 4 weeks. Conclusion: An sFlt-1/PlGF ratio of ≤22.2 is potentially indicative of PE absence within 4 weeks in twin pregnancies

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AimPouch of Douglas obliteration, which prevents exteriorization of the uterus, increases surgical morbidity in patients with placenta previa. We aimed to identify magnetic resonance imaging features that can predict pouch of Douglas obliteration preoperatively.MethodsWe retrospectively assessed 39 women with posterior placenta previa who underwent magnetic resonance imaging for the preoperative assessment of placenta accreta spectrum. We defined the angle formed by the anatomical conjugate line (based on pelvimetry) and the cervical canal as the cervical inclination angle, which was measured on sagittal T2-weighted magnetic resonance imaging. Subsequently, we analyzed the correlation between the cervical inclination angle and pouch of Douglas obliteration.ResultsThe median maternal age was 34 years (range, 22–44 years) and 26 (66.7%) women delivered at term. The median cervical inclination angle was 98° (range, 71–128). Pouch of Douglas obliteration was confirmed in six patients (15.4%). The cut-off value of the cervical inclination angle for the prediction of pouch of Douglas obliteration was 102° with a sensitivity of 66.7%, specificity of 78.8%, positive predictive value of 36.4%, and negative predictive value of 92.9% (area under the curve, 0.83).ConclusionsMeasuring the cervical inclination angle may help in ruling out an obliteration of the pouch of Douglas. It may also be useful in the operative management of women with posterior placenta previa. However, caution should be exercised when generalizing the results of this study because of the small sample size, which makes the results prone to bias.</div

Fbxl4 Regulates the Photic Entrainment of Circadian Locomotor Rhythms in the Cricket Gryllus bimaculatus

Photic entrainment is an essential property of the circadian clock that sets the appropriate timing of daily behavioral and physiological events. However, the molecular mechanisms underlying the entrainment remain largely unknown. In the cricket Gryllus bimaculatus, the immediate early gene c-fosB plays an important role in photic entrainment, followed by a mechanism involving cryptochromes (crys). However, the association between c-fosB expression and crys remains unclear. In the present study, using RNA-sequencing analysis, we found that five Fbxl family genes (Fbxl4, Fbxl5, Fbxl16, Fbxl-like1, and Fbxl-like2) encoding F-box and leucine-rich repeat proteins are likely involved in the mechanism following light-dependent c-fosB induction. RNA interference (RNAi) of c-fosA/B significantly downregulated Fbxls expression, whereas RNAi of the Fbxl genes exerted no effect on c-fosB expression. The Fbxl genes showed rhythmic expression under light-dark cycles (LDs) with higher expression levels in early day (Fbxl16), whole day (Fbxl-like1), or day-to-early night (Fbxl4, Fbxl5, and Fbxl-like2), whereas their expression was reduced in the dark. We then examined the effect of their RNAi on the photic entrainment of the locomotor rhythm and found that RNAi of Fbxl4 either disrupted or significantly delayed the re-entrainment of the locomotor rhythm to shifted LDs. These results suggest that light-induced c-fosB expression stimulates Fbxl4 expression to reset the circadian clock