Explore the vast range of titles available.

In this longitudinal study of 77 pregnant women, we examined how eye movement density (EMD) measured at 34 to 36 weeks’ gestation related to child development at age 3 years, using two developmental assessment tools. Fetal eye movements were recorded for 60 min. Data from 41 children with complete follow-up at age 3 years were analyzed. EMD was calculated as the number of eye movements per minute during periods with eye movement activity, which reflects the active behavioral state considered a precursor to rapid eye movement (REM) sleep. At 3 years, development was assessed using the Kinder Infant Development Scale and autism-related traits using the Social Responsiveness Scale-2. Sleep was evaluated with caregiver-completed questionnaires and sleep logs at 6 months, 1 year, and 3 years. Higher fetal EMD was associated with greater receptive and expressive language development, whereas lower EMD was linked to higher restricted and repetitive behavior (RRB) scores and an increased likelihood of clinically significant RRB. Moreover, lower EMD predicted later bedtimes at age 1 year. These findings suggest that fetal EMD reflects early maturation of neural circuits and may serve as a noninvasive early biomarker for identifying children at risk of developmental and behavioral difficulties.

Fetal growth restriction (FGR) and pre-eclampsia with fetal growth restriction (PE/FGR) are high-risk perinatal diseases that may involve high levels of human chorionic gonadotropin (hCG) and mitochondrial dysfunction. However, little is known about how these factors affect placental function. We investigated how mitochondrial dysfunction and high hCG expression affected placental function in unexplained FGR and PE/FGR. We observed elevated expression of hCGβ and growth differentiation factor 15 mRNA and protein levels in the placenta with both diseases. Likewise, antiangiogenic factors, such as Ang2, IP10, sFlt1, IL8, IL1B, and TNFα, were also upregulated at the mRNA level. In addition, the expression of COXI and COXII which encoded by mitochondrial DNA were significantly decreased in both diseases, suggesting that mitochondrial translation was impaired. Treatment with hCG increased Ang2, IP10, IL8, and TNFα mRNA levels in a dose-dependent manner via the p38 and JNK pathways. Mitochondrial translation inhibitors increased hCGβ expression through stabilization of HIF1α, and increased IL8 and TNFα mRNA expression. These results revealed that high expression of hCG due to mitochondrial translational dysfunction plays an important role in the pathogenesis of FGR and PE/FGR.

Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocalization of newborn neurons in the hippocampus. We confirmed that neurons newly generated from neural stem/progenitor cells (NS/PCs) are integrated into the granular cell layer in the adult hippocampus; however, prenatal VPA treatment altered the expression in NS/PCs of genes associated with cell migration, including CXC motif chemokine receptor 4 (Cxcr4), consequently increasing the ectopic localization of newborn neurons in the hilus. We also found that voluntary exercise in a running wheel suppressed this ectopic neurogenesis and countered the enhanced seizure susceptibility caused by prenatal VPA exposure, probably by normalizing the VPA-disrupted expression of multiple genes including Cxcr4 in adult NS/PCs. Replenishing Cxcr4 expression alone in NS/PCs was sufficient to overcome the aberrant migration of newborn neurons and increased seizure susceptibility in VPA-exposed mice. Thus, prenatal exposure to an AED, VPA, has a long-term effect on the behavior of NS/PCs in offspring, but this effect can be counteracted by a simple physical activity. Our findings offer a step to developing strategies for managing detrimental effects in offspring exposed to VPA in utero.

Aesthetic patients in East Asia are commonly concerned about small apparent eye size. Simultaneous treatment of the glabellar and lateral canthal areas with botulinum neurotoxin has potential to provide improvements. This case series evaluated changes in eye size following treatment of these two areas using standard on-label doses of onabotulinumtoxinA in patients from Japan or China. Outcomes were assessed based on standardised frontal photographs taken before and after treatment (at rest, maximum smile, and maximum frowning). Changes in eye size were examined using a 4-point Likert scale, as evaluated by three independent groups: six injectors; six non-injecting observers; and treated patients. Furthermore, improvements in overall facial impression were analysed using two established tools: ‘emotional attributes’ and ‘social attributes’. Twenty East Asian subjects were included (n = 17 women; mean age: 37.5 ± 6.4 years). The majority of evaluators in all three groups rated patients’ eye size as ‘significantly’ or ‘mildly’ improved post-treatment, whether assessed at rest, when smiling, or during frowning. Furthermore, almost all evaluators noted improvements in one or more emotional and social attributes. This approach has significant potential as a culturally adapted aesthetic technique for improving eye size in East Asian patients. Larger multicentre studies are warranted.

Ovarian carcinosarcoma (OCS) is a rare and aggressive tumor, and the development of its sarcomatous component is believed to be due to epithelial–mesenchymal transition (EMT). The SWIch/sucrose nonfermentable chromatin remodeling factor (CRF) is closely related to EMT; however, the relationship between CRF and EMT in OCS remains unclear. In this study, we analyzed the protein expression of CRFs, including ARID1A and SMARCA4, and their downstream mRNA expression in 28 OCS cases, two fallopian tube CS cases, and one peritoneal CS case. ARID1A and SMARCA4 exhibited a histological type‐specific loss of protein expression in 5 of 11 (45%) endometrioid cases and all 5 serous/homologous OCS cases, respectively. The mRNA analysis suggested that sarcomatogenesis is induced by the transforming growth factor‐β and Hippo signaling pathways, both of which regulate YAP1. Immunostaining for YAP1 suggested YAP1‐associated sarcomatogenesis in the CRF‐retained group, whereas YAP1‐unassociated sarcomatogenesis was suggested in the CRF‐reduced group. High‐grade serous carcinoma cell line experiments showed that the transcriptome of the SMARCA4‐knockdown group showed lower expression of the epithelial gene CDH1 and higher expression of mesenchymal genes such as VIM, ZEB1, and SNAI1 than the control group. Moreover, cell adhesion disappeared and cell morphology changed to a spindle shape, indicating sarcomatogenesis. In conclusion, this study reveals a mechanism for sarcoma development in OCS and provides novel therapeutic possibilities. We analyzed the protein expression of chromatin remodeling factors (CRFs), including ARID1A and SMARCA4, and their downstream mRNA expression in 31 carcinosarcoma (CS) cases, including fallopian tube CS and peritoneal CS, to identify the mechanism of sarcomatogenesis. SWI/SNF‐retained ovarian CS (OCS) may be sarcomatogenesis through the Hippo signaling pathway, whereas SWI/SNF‐reduced OCS may be sarcomatogenesis through different pathways, including epigenomic regulation.

Recently, adult stem cells have been identified in several mature tissues. The human endometrium is responsive to sex steroid hormone. It undergoes extraordinary growth in a cyclic manner and is shed and regenerated throughout a woman’s lifetime. It has been proposed that the human endometrium may contain a population of stem cells, which are responsible for its remarkable regenerative ability. It is also suggested that stem-like cells exist in cancer tissues. Stem-like cell subpopulations, referred to as “side population” (SP) cells, have been identified in several tissues and tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Recently, we isolated and characterized the SP cells in normal human endometrium and in an endometrial cancer (EC) cell line. Endometrial SP cells can function as progenitor cells. EC SP cells show the following: (1) reductions in the expression levels of differentiation markers; (2) long-term repopulating properties; (3) self-renewal capacity; (4) enhancement of migration and podia formation; (5) enhancement of tumorigenicity; and (6) bipotent developmental potential (tumor cells and stroma-like cells), suggesting that these SP cells have cancer stem-like cell features. We review the articles that show the presence of stem cells in normal endometrium and EC cells and demonstrate the results of our studies.

Reconstitution of the germ cell lineage using pluripotent stem cells provides a unique platform to deepen our understanding of the mechanisms underlying germ cell development and to produce functional gametes for reproduction. This study aimed to establish a culture system that induces a robust number of primordial germ cell-like cells (PGCLCs) from common marmoset ( Callithrix jacchus ) embryonic stem cells. The robust induction was achieved by not only activation of the conserved PGC-inducing signals, WNT and BMP4, but also temporal inhibitions of WNT and retinoic acid signals, which prevent mesodermal and neural differentiation, respectively, during PGCLC differentiation. Many of the gene expression and differentiation properties of common marmoset PGCLCs were similar to those of human PGCLCs, making this culture system a reliable and useful primate model. Finally, we identified PDPN and KIT as surface marker proteins by which PGCLCs can be isolated from embryonic stem cells without genetic manipulation. This study will expand the opportunities for research on germ cell development and production of functional gametes to the common marmoset.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by behavioral abnormalities. Although mouse models have been widely adopted to recapitulate the pathology of ASD, the identification of specific neural abnormalities responsible for autistic-like behavior has remained challenging. Here we provide insight into this causal relation by identifying the critical period and cell type responsible for the development of such behavior in ASD model mice with a Chd8 mutation. We find that Chd8 mutation induced at embryonic day 14.5 gives rise to ASD-like behavioral phenotypes, including abnormal social interaction and increased anxiety-like behavior, as well as to accelerated cell-cycle exit and differentiation in ventral progenitor cells. Restoration of Chd8 expression in ventral progenitor cells ameliorates both the behavioral phenotypes and aberrant ventral differentiation in Chd8 mutant mice. Our findings indicate that Chd8 mutation during the midfetal period—in particular, in ventral progenitor cells—contributes to the development of autistic-like behavior. Midfetal Chd8 mutation in ventral progenitor cells disrupts neurogenesis, leading to altered neuronal development and autistic-like behaviors in mice. Restoring Chd8 in these cells rescues both neural defects and behavior.

Background Trachelectomy was developed as a fertility-sparing surgery for early-stage cervical cancer in patients of childbearing age. The purpose of this study is to evaluate oncologic and obstetric outcomes and complications after abdominal trachelectomy. Methods We began to perform abdominal trachelectomy in 2005. Our institutional review board approved this clinical study, and fully informed consent was obtained from each patient. The medical records of patients who underwent trachelectomy were retrospectively reviewed. Results We performed 151 abdominal trachelectomies (89 radical trachelectomies, 48 modified radical trachelectomies, and 14 simple trachelectomies). The median age of the patients was 33 years, and the median postoperative follow-up period was 61 months. Although one patient experienced recurrence at the preserved cervix, none died after treatment. A total of 61 patients attempted to conceive after trachelectomy, and 21 pregnancies were achieved in 15 women. Hence, the pregnancy rate among patients who attempted to conceive was 25%. Fifteen babies were delivered by cesarean section between gestational weeks 23 and 37. Six babies were delivered at term. Six cases of preterm premature rupture of the membranes occurred. Varices appeared around the uterovaginal anastomotic site in five patients. Conclusions Our data indicate that the oncologic outcome was excellent but infertility treatment was necessary to achieve the majority of conceptions. Additionally, preterm premature rupture of the membranes and premature delivery were frequently observed. An improved pregnancy rate and prevention of complications during pregnancy are issues that should be addressed in future studies.

Background: Tracking gestational weight gain (GWG) during pregnancy makes it possible to optimize pregnancy outcomes, and GWG growth curves are well suitable for this purpose. The GWG guidelines for Japanese were revised in 2021. However, currently, there are no GWG growth curves to guide women on how to gain weight to meet these guidelines.Methods: Using data on 96,631 live births from the Japan Environment and Children’s Study (JECS), we created descriptive GWG percentile curves estimating the trajectory of GWG required to meet the GWG guidelines stratified by pre-pregnancy body mass index (BMI). For both analyses, Bayesian mixed models with restricted cubic splines adjusted for maternal characteristics were used.Results: GWG curves substantially differed by pre-pregnancy BMI and were higher among multiparas and those with lower maternal age and with no previous disease. We estimated that underweight, normal weight, overweight, and obese women who gain 8.4 to 11.1 kg, 6.4 to 9.1 kg, 3.8 to 6.5 kg, and <1.9 kg at 30 weeks of gestation are on the trajectory to reach the new guidelines at 40 weeks of gestation.Conclusion: We provide GWG percentiles curves for Japanese women, as well as GWG trajectory curves to meet the new GWG recommendations. These results may help pregnant women monitor weight during pregnancy.