Hypoxia plays a critical role in regulating vascular function, with endothelial mechanosensitive proteins, such as the piezo-type mechanosensitive ion channel component 1 (Piezo1), emerging as key players in maintaining vascular homeostasis. Piezo1 is essential for nitric oxide-mediated vasodilation and vascular tone regulation. However, the impact of hypoxia on endothelial Piezo1 expression and function remains poorly understood. The present study investigated the regulation of Piezo1 and mechanosensitive-related genes (MRGs) during hypoxic development and their role in fetal growth restriction (FGR). Using publicly available datasets, we identified distinct transcriptional profiles in placental endothelial cells from human FGR pregnancies and human umbilical vein endothelial cells (HUVEC) exposed to hypoxia. Functional enrichment analysis revealed significant changes in pathways related to PI3K-Akt, MAPK, and VEGF signaling and responses to mechanical stimuli. Hypoxia-related transcription factors, particularly HIF-1α and HIF-1β, were enriched in the promoter regions of differentially expressed MRGs, including Piezo1, suggesting a conserved regulatory mechanism. In vitro experiments confirmed hypoxia-induced down-regulation of Piezo1 in HUVEC, while ex vivo studies using a chicken embryo model demonstrated impaired Piezo1-mediated vasodilation following hypoxic development. Combined, these findings highlight the critical role of hypoxia in modulating endothelial Piezo1 expression and function, providing mechanistic insights into vascular dysfunction associated with FGR. The present study provides evidence for the potential to target Piezo1 and HIF-1α signaling as therapeutic strategies to improve vascular outcomes in offspring of pregnancies complicated by hypoxia and FGR.

Next-generation sequencing as an applicable method: from technical basis to use in medical diagnosis.

To evaluate fetal brain midline structures, cortical structures, and brain volume using sonography in cases of fetal growth restriction (FGR) and to compare these findings with those of fetuses demonstrating normal growth. This prospective case-control study included 80 FGR cases and 80 fetuses with normal growth curves between 24 and 37 weeks of gestation. Multiplanar neurosonography was performed in all cases according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guidelines. The corpus callosum (CC; length, thickness, and fastigium distance), cavum septi pellucidi (CSP), sylvian fissure (SF), parieto-occipital fissure (POF), calcarine fissure (CF), insula, olfactory sulcus (OS), and brain volume were evaluated. Measurements were made using the ultrasound device's electronic calipers, and brain volume was calculated using the Virtual Organ Computer-aided Analysis (VOCAL) application. In the FGR group, CSP width, CC length, and thickness were significantly increased, while CCFL and POF depths were decreased (p<0.05, for all). Mean brain volumes were similar in the FGR and control groups (349.30±61.77 vs. 368.42±68.51, p=0.066). In FGR group, middle cerebral artery peak systolic velocity (MCA PSV) was positively correlated with most brain structures but negatively correlated with CC thickness. There was no relationship between cerebroplacental ratio (CPR) and brain volume or fetal brain structures. Our findings showed that FGR affects the fetal brain through neuroanatomical structures such as the CC, CSP, CCFL, and POF during the prenatal period. In our cohort, fetal brain volume did not differ significantly in FGR. Furthermore, there was no association between CPR and fetal brain structures.

Early exposure to lead has known neurocognitive impacts in childhood, but few studies have examined the long-term impacts extending into later adulthood. We estimated associations between prenatal and early postnatal lead exposure and later adulthood cognitive function and examined specific periods of exposure and effect modification by sex. The St. Louis Baby Tooth-Later Life Health study (SLBT) is a prospective cohort study that re-enrolled participants of the Baby Tooth Survey, originally centered in St. Louis, MO, who had donated their deciduous teeth between 1958 and 1972. SLBT participants completed surveys and a battery of cognitive tests in later adulthood. Tooth dentin lead concentrations were assessed using laser ablation inductively coupled plasma mass spectrometry across prenatal (second and third trimesters) and early postnatal periods. Cognitive function was assessed using a computerized cognitive battery taken at home using computers or personal digital devices. We used weighted generalized estimating equations to estimate associations between lead exposure and a composite outcome of later adulthood cognitive function. A total of 715 participants (52% female, mean age at cognitive testing: 62 years) had completed tooth metals analysis. The association between lead and performance on the vocabulary test was positive and statistically significantly different from the other tests. For each part per million (ppm) higher second trimester tooth dentin lead concentration, performance on a composite of tests excluding vocabulary was 0.07 SDs lower (95% CI -0.15 to 0.02). This effect was similar when coadjusting for third trimester and postnatal lead. These findings were driven by females, among whom each 1 ppm higher second trimester lead concentration was statistically significantly associated with 0.16 SD worse cognitive function (95% CI -0.29 to -0.03), equivalent to a 3-year difference in age in the same model. The results were robust to adjustment for additional potential sources of confounding and alternate methods of averaging tooth lead concentrations. We found suggestive evidence for associations between early lead exposures and later adulthood cognitive function, although these only reached statistical significance for second trimester lead exposure among females. A coadjusted analysis suggested the second trimester may be most relevant for later cognitive function.

Pain tolerance varies significantly among humans, with disparities attributable to genetic factors and environmental influences. The developmental origins of health and disease approach postulate that pre- and early postnatal maternal environment affects individuals' health and well-being. In the present study, we aimed to determine the influence of prenatal and early postnatal maternal environment and care on the offspring's physiology and pain response. To this end, we analysed the influence of bidirectional embryo transfer (ET) and cross-fostering (CF) between two mouse lines divergently selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on offspring phenotype, SSIA-related traits and opioid component of SSIA. Our findings reveal that both the fetal development and early maternal care significantly influence the level of SSIA in mice. HA mice born after ET to LA surrogate mothers showed reduced SSIA levels alongside a diminished effect of the opioid antagonist naloxone, suggesting a decreased opioid component in SSIA regulation. This effect was preserved in the F2 generation of individuals originating from ET, but not CF. Additionally, both ET and CF resulted in changes in body weight and body temperature towards an average value of the surrogate or foster maternal line; however, these changes were not preserved in the F2 generation. Together, our findings indicate that maternal influence during fetal development and the early postnatal period may influence physiological parameters, as well as traits associated with stress response. Maternal influence is more pronounced in progeny subject to ET, indicating a stronger influence of the prenatal period.

Galloway-Mowat syndrome type 3 (GAMOS3) is a rare autosomal recessive disorder characterized by the co-occurrence of renal and neurological abnormalities in early childhood, caused by OSGEP gene variants. This study aims to characterize the genetic and phenotypic spectrum of GAMOS3 and evaluate correlations from prenatal imaging features to lifelong neurological and renal manifestations. We retrospectively reviewed the medical records of cases genetically diagnosed with OSGEP-associated GAMOS3 at our center between January 2016 and August 2024. Additionally, a systematic review of reported cases in literature was conducted. The clinical validity of the gene-disease relationship between OSGEP and GAMOS3 was also evaluated in accordance with the ClinGen Gene-Disease Clinical Validity Curation Framework. The postnatal renal and neurological dysfunction was associated with prenatal manifestations, indicating disease progression. Prominent prenatal features included fetal growth restriction (FGR), microcephaly, oligohydramnios, and abnormal cranial imaging. Notably, FGR worsened with advancing gestation, predominantly affecting fetal head and abdominal growth while sparing long bones. Fetal central nervous system magnetic resonance imaging revealed uncommon findings such as abnormal sulcation and increased T2 signal in the white matter, suggestive of myelination defects or leukoencephalopathy. Trio-based medical exome sequencing identified novel variants in the OSGEP gene within this cohort, expanding the known genetic spectrum of GAMOS3. Furthermore, the gene-disease relationship between OSGEP and GAMOS3 was conclusively validated as "Definitive" according to clinical-genetic criteria. This study provides a comprehensive overview of the clinical phenotypes and genetic spectrum of GAMOS3, spanning from the prenatal period throughout the life course.

Associations between Molar-Incisor Hypomineralisation and drinking water and groundwater parameters in Lower Austria: Results from an observational study.

Background Maternal distress is a growing global concern in health science. It is the normal response of perinatal women to the changes and demands encountered during the transition to motherhood. Since it influences maternal functioning and child outcomes, it is crucial to identify the factors that affect maternal distress to prevent or lessen its impact. Objective This article aims to synthesize all the factors contributing to maternal distress among first-time mothers. Methods The review included 71 English-language studies from Scopus, Web of Science, and PubMed in Psychology and Nursing (2015–2024), with the last search conducted in November 2024. The Newcastle-Ottawa and Quality assessment with Diverse Studies were used for quality evaluation. Results Through narrative synthesis of the studies, various factors—such as psychological, social, biological, individual, situational, infant-related, paternal, pregnancy-related, and birth-related—were identified and classified into protective and risk factors. From this review, factors such as social support, maternal age, and previous psychiatric history were identified as consistent. Conclusion Only a few studies have focused on exploring factors associated with maternal distress among first-time mothers during the prenatal period rather than the postnatal period. This review can help address the gap in the literature and assist in early screening and prevention of perinatal distress. The review was registered with PROSPERO (CRD420251061749).

Sex-dependent effects of early-life paracetamol exposure on behavior and monoamines in the rat central nervous system.

Infertility refers to a couple's inability to conceive after a period of normal, unprotected sexual activity or to carry a pregnancy to full term. This study investigated the correlation between sperm DNA fragmentation index (DFI) and routine semen parameters, as well as its predictive value for in vitro fertilization (IVF) outcomes. A total of 158 infertile patients undergoing IVF-embryo transfer (ET) from September 2021 to February 2023 were enrolled. Based on DFI levels, patients were divided into a low-DFI group (DFI ≤ 25%, n=94) and a high-DFI group (DFI > 25%, n=64). Routine semen parameters were analyzed and correlated with DFI levels. DFI showed significant negative correlations with sperm motility, progressive motility (PR), and non-progressive motility (NP), and a positive correlation with immotility (IM) (P<0.05).Receiver operating characteristic (ROC) analysis revealed that combined semen parameters had the highest diagnostic value for assessing DFI (AUC = 0.998). Additionally, significant differences were observed between groups in human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates (P<0.05). We conclude that sperm DFI is negatively associated with sperm motility parameters and positively associated with immotility. .It has a predictive value for clinical IVF outcomes and may serve as a useful indicator in infertility assessment.

Objective: Postpartum maternal readmission is a significant burden for patients as well as the health system. Postpartum readmission rate is a known factor in evaluating quality of care and in guiding potential beneficial interventions. Use of the Robson Group (RG) classification, initially used for analysis of cesarean section (CS) rates, has been recently expanded to evaluate other obstetrical outcomes. We aimed to describe the rates of postpartum maternal readmission across RG classification and to identify risk factors among the different maternity groups. Study Design: We carried out a retrospective register-based cohort study of all women who delivered >24 weeks gestation at a tertiary medical center over an 18-year period, with classification into the 10 RGs. Rates of postpartum readmission within 42 days of delivery were calculated for each group, as well as indications for readmission. The risk for maternal readmission was analyzed by univariate binary logistic regressions with comparison of results among RC groups, as well as by multivariate analysis models. Results: During the study period, 296,768 deliveries were classified according to Robson Group (RG) classification. The overall readmission rate for the study population was 0.5%. The following groups had a significant risk of readmission: RG 9 (transverse lie), 1.9%; RG 8 (multifetal pregnancies), 1.90=3%; RG 7 (multiparous breech pregnancies) 1.2% and RG2 (nulliparous pregnancies > 37 w, labor induction or prelabor cesarean), 1.2%. The most common indication for readmission among all RGs was fever (61.4%). Conclusions: Postpartum readmission rates varied among the RGs. The highest-risk groups were those with a higher risk of operative delivery, prolonged labor, or malpresentations. Interventions aimed to reduce the number of women in these groups; these included use of external cephalic version, vaginal delivery of breech, and multifetal pregnancies, all of which may be beneficial.

Early life experiences and the process of exploration play a vital role in shaping brain development and lifelong learning. In March 2020, population-wide restrictions were imposed due to the COVID-19 pandemic. It remains to be determined whether having been raised under the global stress and restrictions of COVID-19 has influenced children's development as they enter formal schooling. The aim of this study was to examine the extent to which having more than 50% of one's first year of life and/or prenatal period in the COVID-19 era influences the developmental trajectory in preschool. The study compared 3- to 5-year-old children born before the pandemic (n = 63) with those who were five months or younger at its onset (n = 40). Variables assessed included executive function skills, vocabulary, and common developmental domains. Using the BRIEF-P as a standardized measure of executive function, the results demonstrate that the pandemic-born cohort exhibit greater impairments than those born before the pandemic. There was also a significant increase in reports of speech and language therapy enrollment; frequent ear infections; diagnoses of hearing, speech, or language impairments; and delays in reaching developmental milestones. The pandemic-born cohort additionally reported delays in fine motor skills compared to the pre-pandemic cohort. The present study underscores the urgent need for additional resources to better support children in this cohort as they begin formal schooling.

While some anatomical brain asymmetries are seen across primates, the earlier appearance and larger depth of the right superior temporal sulcus (STS) is specific to human foetuses. Interestingly, the degree of STS asymmetry varies between foetuses, and it has been shown that this interindividual variability is related to the functional lateralization of the language network in school-aged children. It remains unclear, however, whether it is also indicative of language localization and functioning shortly after birth. In the present longitudinal study, we prospectively examined the predictive value of foetal STS asymmetry for neonates' language lateralization and neural speech discrimination. We measured the STS depths and volumes in neurotypical foetuses (N = 35) using foetal MRI. After birth, we investigated the neonates' haemodynamic response to forward and backward speech using functional near-infrared spectroscopy. We hypothesized that less rightward asymmetry of the STS depths in the foetal brain is related to increased left language lateralization and to a greater haemodynamic difference between speech conditions in the left hemisphere in neonates. While the foetuses demonstrated an overall rightward asymmetry of the STS depths and volumes, the degree of asymmetry varied between individuals. After birth, the group activated left frontal and right temporal regions during the speech discrimination paradigm. Again, there was variability in the degree of neural activation in response to speech. Importantly, we found that children with a foetal STS depth asymmetry towards the left hemisphere activated their right hemisphere less for forward speech (r = -0.58, P = 0.002) and differentiated less between forward and backward speech in their right hemisphere (r = -0.48, P = 0.014). Contrary to our initial hypothesis, the results suggest that an earlier structural development of the left temporal lobe goes along with reduced involvement of the right hemisphere, rather than an increased involvement of the left hemisphere, during neural speech discrimination. Given that rightward asymmetry of language-related brain areas has been associated with weaker language abilities, the present study provides important preliminary data regarding the neural underpinnings of language development during the prenatal and early postnatal period.

Xylazine, an alpha-2 adrenergic agonist veterinary sedative, has emerged as a frequent adulterant in illicit opioids, contributing to the ongoing "tranq dope" crisis. Its effects on human pregnancy are largely unknown, posing new challenges in obstetric addiction medicine. We present the case of a 25-year-old woman (G4P2113) with opioid use disorder who unknowingly used fentanyl adulterated with xylazine throughout pregnancy. She developed preeclampsia with HELLP syndrome, requiring urgent preterm cesarean delivery at 34 weeks. The neonate was treated for neonatal abstinence syndrome. Four days postpartum, the patient-discharged without medication for opioid use disorder-suffered intractable vomiting from withdrawal, leading to a Mallory-Weiss tear with massive hemorrhage and cardiac arrest. She required intensive care with transfusions, endoscopic hemostasis, and mechanical ventilation. Upon extubation, she disclosed fentanyl-xylazine ("tranq") use. She was transitioned to buprenorphine maintenance with supportive care for xylazine withdrawal and discharged in improved condition. We review the sparse human literature on xylazine exposure in pregnancy and relevant animal studies. Human data confirm placental transfer of xylazine, with umbilical cord assays detecting exposure, and suggest that xylazine may contribute to maternal CNS depression and neonatal sedation. Animal models demonstrate dose-dependent uterine vasoconstriction, reduced uteroplacental blood flow, fetal growth restriction, and pregnancy loss. We discuss management considerations for pregnant patients using xylazine-adulterated opioids, including challenges in diagnosis, withdrawal management, and the need for expanded harm-reduction strategies. This case and review highlight the urgent need for surveillance and evidence-based protocols to address xylazine in the perinatal setting.

Association between prenatal, pre-pregnancy rainfall and adult obesity: Findings from the Community Behavior and Attitude Survey in Tuvalu (COMBAT).

ABSTRACTSepto‐optic dysplasia (SOD) is a rare condition with highly heterogenous clinical manifestations and can be a diagnostic challenge. It can present with pituitary hormone deficiencies, growth failure, visual impairment, and neurological symptoms. SOD can be diagnosed at different time points—from the prenatal period to childhood. Our team cared for a baby girl who presented with recurrent hypoglycaemia, conjugated hyperbilirubinemia, and hormonal deficiencies, prompting investigations that resulted in an early diagnosis of SOD. This case report highlights the importance of considering neuroimaging to exclude septo‐optic dysplasia in term infants with recurrent hypoglycaemia, low cortisol, and growth hormone levels, as timely diagnosis with early hormone replacement reduces long‐term morbidities.

Multifetal pregnancies have increased preeclampsia risk, but the underlying pathogenesis may differ from that of singletons. It remains unclear whether twin placentas show molecular signs of preeclampsia synchronously. We performed RNA sequencing on 32 individual placental samples from twin gestations grouped by preeclampsia status: 24 dichorionic twin (DT) and 8 monochorionic twin gestations. Ten singleton placentas from preeclamptic pregnancies were also analyzed. A benchmark data set (GSE203507, GSE114691, and GSE1482410) and a test data set (GSE190973) comprised 71 early onset preeclampsia and 69 control singleton placentas. Differential abundance analysis was conducted, and machine learning was used to derive a novel 98-transcript classification signature (accuracy >0.97 in benchmark and test data sets). Across 7 groups, 2946 transcripts were differentially modulated (likelihood-ratio test; false discovery rate <0.05). Placental signature scoring distinguished normotensive from early onset preeclampsia in GSE203507 singletons (P<0.0001) although normotensive DTs did not differ from DTs with preeclampsia (Kruskal-Wallis/Dunn). Notably, some twin placentas without clinical preeclampsia exhibited preeclampsia-like profiles. Linear mixed-effects regression, which accounted for intertwin correlation structure, revealed increasing signature scores across singleton and DT groups (all P<0.01): normotensive singletons<normotensive DT<DT with preeclampsia<singletons with preeclampsia. Functional analysis in twins showed preeclampsia-like dysregulation but with pronounced variability. Intertwin divergence was more prominent in DT than in monochorionic twin samples, regardless of clinical diagnosis. These findings highlight the complexity of preeclampsia pathology in twins. In DT pregnancies complicated by preeclampsia, placental involvement may be asymmetrical, suggesting that disease may arise from a single affected placenta; however, these results require replication.

Ultrasonography has emerged as a transformative tool in buffalo reproduction, offering non-invasive, real-time insights into the anatomical and physiological aspects of the reproductive tract. In addition to its routine application for preg nancy diagnosis, ultrasonography is crucial for monitoring fetal development, diagnosing fetal anomalies, and identify ing conceptus loss. This helps in timely interventions by diagnosing non-pregnant animals or those having pregnancy issues, which can significantly improve reproductive outcomes. The ability of ultrasonography to enhance our under standing of follicular dynamics in buffaloes has significantly improved fertility management practices. By closely moni toring follicle development and ovulation timing, veterinary professionals can optimize breeding schedules and improve the success rates of artificial insemination. The combination of high-resolution B-mode imaging and Doppler modal ities aids in predicting fertility outcomes in various obstetrical conditions such as uterine torsion. Clinicians can make informed decisions regarding treatment options and prognosis by assessing blood flow to the reproductive organs and evaluating the uterine health. This review emphasises the routine application of ultrasonography for pregnancy diagnosis and the identification of reproductive disorders, while also exploring its advanced use in obstetrics, assisted reproductive technology, and male reproduction. As this technology continues to evolve, it promises to play an increasingly vital role in advancing buffalo reproduction.

Human sexual development begins in the prenatal period and continues throughout life, shaped by both biological and psychosocial factors. Somatic development leads to reproductive maturity through several stages regulated by the hypothalamic-pituitary-gonadal axis. Psychosexual development, described in classical theories such as Freud's and in contemporary models, emphasizes the development of gender identity and sexual behaviors from infancy through early and middle childhood into adolescence, a period characterized by the integration of sexual and emotional components. This developmental trajectory evolves from a biologically driven process into a conscious, socially shaped phenomenon through concretization, mentalization, and socialization. To synthesize current knowledge, this paper is based on a literature review conducted across multiple databases, with studies selected and evaluated for relevance to both somatic and psychosexual development. Understanding the dynamics of these processes is essential for clinical practice, sexual education, and health prevention. It emphasizes integrated clinical practices that employ a multidisciplinary approach, incorporating both medical treatment and psychological support, particularly in the care of children and adolescents with disorders of sexual development. This article presents a comprehensive overview of human sexual development from the prenatal period through adolescence, considering its somatic and psychosexual aspects.

The prenatal period, childhood, and adolescence are critical periods of development characterized by high plasticity. As an extension of the Developmental Origins of Health and Disease (DOHaD) paradigm, known as Origins of Paternal Health and Disease (POHaD), recent studies in rodents provide evidence that paternal obesity is associated not only with infertility but also with an increased risk of metabolic disorders in the offspring. In rodents, litter size reduction is used to induce lactational overfeeding by increasing the amount of breast milk to pups, which causes metabolic and reproductive disorders in adulthood. This work evaluated the metabolic and reproductive alterations in the offspring of males raised in normal or small litter (SL) in the prepubertal period and in adult life. The results show that paternal obesity due to early overfeeding affects the offspring in a sex-specific manner. During the prepubertal period, male offspring of SL fathers showed decreased Lee index, tibia length, and HDL plasma levels, and increased weight of gastrocnemius muscle, while female offspring of SL fathers only showed reduced HDL plasma levels. In adulthood, male offspring of overfed males showed glucose intolerance and reduced food intake and triglycerides plasma levels, signs of metabolic dysfunction. Female offspring of overfed males showed delayed puberty onset and higher prevalence of infertile periods in the estrous cycles, indicating a potential susceptibility to reproductive dysfunction. The results of the current study show that paternal obesity due to early overfeeding affects energy balance and reproduction of their offspring in a sex-specific manner.