Early Stages Of Gestation Research Articles

Lipid peroxidation products and superoxide dismutase activity in women depending on the phosphatidylethanol level in the first trimester of pregnancy

Background. Even small amounts of alcohol have an extremely negative effect on the fetus, especially in the early stages of gestation. It is known that ethanol promotes the formation of free radicals, but there is no data on the nature of the oxidative stress development in pregnant women depending on its blood level.The aim. To assess the level lipid peroxidation products and superoxide dismutase activity in the first trimester of pregnancy for women, who consumed alcoholic bevera ges, depending on the phosphatidylethanol (PEth) level in the blood.Materials and methods. The study included 165 women in the first trimester of pregnancy aged 18 to 40 years. To identify the fact and amount of alcohol consumption, the direct biomarker of alcohol 16:0/18:1PEth in blood plasma was performed using high-performance liquid chromatography with tandem mass spectrometry. Depending on the concentration of PEth, groups of women consuming different doses of alcohol were identified: group 1 – PEth concentration < 8 ng/ml (non-drinkers; n = 63); group 2 – PEth concentration from 8 to 45 ng/ml (drinkers of less than 1 dose; n = 66); group 3 – PEth concentration ≥ 45 ng/ml (drinkers of more than 1 dose; n = 36). The content of lipid peroxidation products and superoxide dismutase activity was determined by spectrophotometric methods.Results. It was found that lipid peroxidation intermediates level in the groups of women who consume alcohol, regardless of PEth 16:0/18:1 level in blood plasma, was significantly higher compared with the control (p < 0.05). The superoxide dismutase activity was higher in the group of pregnant women who consumed less than 1 dose of alcohol compared with the control (p < 0.05) and the group who consumed one or more doses of alcohol (p < 0.05).Conclusion. The obtained results indicate the activation of lipid peroxidation processes in the first trimester of pregnancy regardless of the dose of alcohol-containing products consumed.

Abnormal microRNA expression profile at early stages of gestation in pregnancies destined to develop placenta previa.

Placenta previa is the abnormal implantation of the placenta into the lower segment of the uterus, is associated with adverse maternal and fetal outcomes such as placenta accreta spectrum disorders, antepartum and postpartum hemorrhage, fetal growth restriction, prematurity, stillbirth and neonatal death, thrombophlebitis, and septicemia. The aim of the study was to assess retrospectively how the later onset of placenta previa affects the microRNA expression profile in the whole peripheral blood during the first trimester of gestation. Regarding the occurrence of the association between aberrant microRNA expression profiles at early stages of gestation and later onset of various pregnancy-related complications, we selected for the study pregnancies developing placenta previa as the only pregnancy-related disorder. In total, 24 singleton pregnancies diagnosed with placenta previa that underwent first-trimester prenatal screening and delivered on-site within the period November 2012-May 2018 were included in the study. Overall, 80 normal pregnancies that delivered appropriate-for-gestational age newborns after completing 37 weeks of gestation were selected as the control group based on the equality of the length of biological sample storage. Downregulation of multiple microRNAs (miR-20b-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-103a-3p, miR-130b-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-210-3p, miR-342-3p, and miR-574-3p) was observed in pregnancies destined to develop placenta previa. The combination of seven microRNAs (miR-130b-3p, miR-145-5p, miR-155-5p, miR-181a-5p, miR-210-3p, miR-342-3p, and miR-574-3p) showed the highest accuracy (AUC 0.937, p < 0.001, 100.0% sensitivity, 83.75% specificity) to differentiate, at early stages of gestation, between pregnancies with a normal course of gestation and those with placenta previa diagnosed in the second half of pregnancy. Overall, 75% of pregnancies destined to develop placenta previa were correctly identified at 10.0% FPR. Consecutive large-scale analyses must be performed to verify the reliability of the proposed novel early predictive model for placenta previa occurring as the only pregnancy-related disorder.

Associations of maternal serum ferritin levels across gestation with gestational diabetes mellitus: A longitudinal cohort study.

The longitudinal changes in maternal serum ferritin (SF) levels across gestation, which indirectly reflect iron supplementation, have not been extensively investigated in relation to gestational diabetes mellitus (GDM). We conducted a retrospective cohort study at a tertiary maternal hospital in Shanghai. Women with SF concentration measurements at 8.0-13.6 weeks' gestation (GW), 29.0-31.6 GW, and an oral glucose tolerance test (OGTT) at 24-28 GW were included. We utilized logistic regression analysis to assess GDM association with maternal SF levels and longitudinal changes. The study included 17 560 women, with 2160 (12.3%) participants diagnosed with GDM. Adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for GDM across increasing quartiles of SF concentrations at 8.0-13.6 GW were 1.00 (reference), 1.139 (95% CI: 1.012-1.283), 1.093 (95% CI: 0.969-1.233), and 1.248 (95% CI: 1.111-1.403). Similarly, at 29.0-31.6 GW, increasing quartiles of SF concentrations were associated with higher adjusted ORs for GDM: 1.00 (reference), 1.165 (95% CI: 1.029-1.320), 1.335 (95% CI: 1.184-1.505), and 1.428 (95% CI: 1.268-1.607). Pregnant women with higher SF levels (upper 25th percentile) at 8.0-13.6 GW had a reduced GDM risk if their SF levels decreased to the lower 25th percentile at 29.0-31.6 GW. Conversely, the subgroup with higher SF levels (upper 25th percentile) at both time points had the highest incidence rate of GDM (15.3%, 1.235 [95% CI: 1.087-1.404]). Maternal SF levels independently and positively associated with GDM risk during early and late gestational stages. Considering the increased GDM risk, routine iron supplementation for iron-replete women is questionable.

Synthesis of cytokines during physiological pregnancy

The article is devoted to the study of the level of pro- and anti-inflammatory cytokines in women with a physiological pregnancy, which is of great importance in obstetrics. Studying the synthesis of cytokines makes it possible to identify disturbances in the course of pregnancy, which is of great practical importance. The authors conducted a study of the level of cytokines in women with physiological pregnancy. Purpose of the study: to study the serum concentration of pro-inflammatory (IL-1β, IL-6, TNFα, IFNγ) and anti-inflammatory (IL-4, IL-10) cytokines in the dynamics of physiological pregnancy. The level of serum cytokines was studied in 94 women with a physiologically progressing pregnancy, who were registered with advisory clinics No. 14, No. 26, and No. 28 in Bukhara. The age of pregnant women ranged from 21 to 37 years, averaging 26.3±1.5 years. When compiling groups by trimester of pregnancy, it was revealed that: 35 women were in the first trimester of pregnancy; in 31 – the second trimester; and in 28 women – the third trimester of pregnancy. The control group consisted of 30 practically healthy non-pregnant women who were comparable in age. The levels of cytokines 1β, IL-6, TNFα, IFNγ, IL-4, and IL-10 was determined in peripheral blood serum using a set of reagents produced by Cytokin LLC (St. Petersburg, Russia) using the ELISA method according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using Student’s t-test using the standard Windows 2000 statistical software package. An increase in the level of proinflammatory cytokines (IFNγ, TNFα) was detected in the early stages of gestation compared with data from healthy non-pregnant women, which persisted in the second half of pregnancy against the background of an increase in anti-inflammatory cytokines (IL-4, IL-10). In the third trimester of pregnancy, a further increase in the serum level of pro-inflammatory cytokines (IL-1β, TNFα, IFNγ) was observed. The results of the studies indicate that at the level of the cytokine network there are mechanisms of fetoprotection, the violation of which can be the cause of pregnancy pathology.

Prevalence and associated factors of self-medication among pregnant women in Sodo Town, Southern Ethiopia.

Self-medication is a widespread practice among pregnant women worldwide, with 44.55% practicing it. However, it may lead to incorrect diagnosis, inappropriate treatment, and failure to recognize contraindications. The adverse effects of self-medication are often unknown, and they pose potential risks to maternal and fetal health. This study aimed to address the gap in research on the prevalence and associated factors of self-medication among pregnant women in Southern Ethiopia, and to promote effective strategies and interventions. A community-based cross-sectional study was conducted among 425 pregnant women in Sodo Town from April to June 2021. Participants were enrolled using a two-stage sampling technique. Data were collected using a structured questionnaire and face-to-face interviews. The association between the outcome and independent variables was assessed through bivariate logistic regression analysis. Additionally, multivariable logistic regression analysis was carried out, including variables with an adjusted odds ratio (AOR) accompanied by a 95% confidence interval (CI) and a p-value of less than 0.05, which was considered statistically significant. In this study, pregnant women aged 18-39 years participated with a 100% response rate. The study found that the prevalence of self-medication during pregnancy was 20.5%, with 8.2% using herbal medicine and 12.3% using conventional medicine. A history of self-medication and first-and second-trimester pregnancy were significantly associated with self-medication. A history of self-medication (AOR = 6.31, 95% CI: 4.89, 9.91) and being in the first trimester of pregnancy (AOR = 3.47, 95% CI: 1.63, 7.38) or second trimester of pregnancy (AOR = 2.14, 95% CI: 1.12, 4.08) were associated with a higher likelihood of self-medication. The study found that 20.5% of pregnant women engaged in self-medication. It also identified that a previous history of self-medication and gestational age were factors associated with self-medication. These findings underscore the need for targeted educational programs and policy interventions to mitigate the risks associated with self-medication during pregnancy, particularly in the early stages of gestation.

487. A RARE CASE OF BRONCHOGENIC CYST ESOPHAGUS

Abstract Introduction Bronchogenic cyst is a relatively rare congenital malformation that develops from abnormal budding of the ventral foregut during the early stage of gestation. Histologically, the cyst wall is covered by respiratory-type ciliated epithelium that may include cartilage and bronchial glands. Case report We present a 20 yrs male with chest discomfort during swallowing for 6 months. Evaluated with Upper GI scopy showed smooth mucosal elevation 30-35 cm from incisors. CECT Chest Showed features of Intramural cystic lesion of size 7x7cm.Patient was evaluated and taken up for surgery. Robotic Thoracoscopic cyst excison was done. Intraoperatively 7x7cm cystic lesion in lower esophagus infra carinally. Cyst has no communication with mucosa. Post operatively patient recovered well, Drin removed on 3 rd Post operative day and Patient was discharged on 4 th day. Histopathology showed the cyst wall is covered by respiratory-type ciliated epithelium that may include cartilage and bronchial glands https://1drv.ms/v/s!AklfEcoVwf9chCmLN-FSXBA2yV3B

RISK FACTORS FOR THE DEVELOPMENT OF PLACENTAL DYSFUNCTION ON THE BACKGROUND OF PREGNANT WOMEN GENITAL INFECTIONS

The progress of perinatology revealed new problems related to the gestational process and antenatal protection of the fetus. Among indicators of perinatal morbidity in modern conditions, one of the leading places occupied by placental dysfunction, the frequency of which, according to the data of domestic and foreign scientists ranges from 36% to 60%. It is known that among the many factors that affect the complicated course of pregnancy and perinatal morbidity, infectious factors in modern conditions occupy one of the leading places. Despite certain achievements in elucidating the etiological factors and pathogenesis of the development of placental dysfunction (PD), the issues of diagnosis and treatment of this pathology in pregnant women need further improvement. Thus, the study of links in the pathogenesis of manifestations of placental dysfunction, which develops during pregnancy in the early stages of gestation against the background of genital infections, is relevant and promising.The purpose. To assess the risk factors for the development of placental dysfunction in pregnant women with genital infections.Material and methods. The retrospective comparative study included 55 women who gave birth after involuntary childbirth according to the regional perinatal center of Chernivtsi, who had signs of placental dysfunction and genital infections during pregnancy during the period 2021-2022.Research results. One of the most important factors affecting the fetoplacental system, which leads to the development of chronic PD (CPD), are infections of the TORCH group. Infections during pregnancy, depending on the gestational period, lead to miscarriage, abortion, stillbirth, malformations of the child, cerebral defects, as well as to acute and chronic neonatal diseases. We conducted a retrospective analysis of risk factors, the frequency and structure of obstetric complications based on the data of 55 birth stories of the regional perinatal center in Chernivtsi for 2021-2022. Manifestations of placental dysfunction against the background of genital infections were studied at different gestational periods. Placental dysfunction occurs at different gestational periods in women of different ages. However, in young people (up to 18 years old) it occurs less often at all stages of gestation, compared to other age categories. A significant number of pregnant women with manifestations of placental dysfunction suffered from infectious diseases in childhood (measles, chicken pox, acute respiratory and viral infections, angina, various disorders of menstrual function (hyperpolymenorrhea, hypomenstrual syndrome, algodysmenorrhea) were quite often observed in pregnant women with manifestations of placental insufficiency. More often, placental dysfunction develops during first births than during repeated births. Cases of stillbirth, spontaneous miscarriages, artificial abortions and ectopic pregnancies often occur in the anamnesis. A number of authors [41] indicate that pregnant women with manifestations of placental insufficiency often experience various complications of the current pregnancy. Modern scientific studies show that almost 80% of pregnant women with genital infections show significant changes in the immune, endocrine and coagulation systems, which lead to a violation of the formation of the fetoplacental complex and a violation of adaptation mechanisms in the mother-placenta-fetus system.Conclusion. Clinical and statistical analysis shows the negative impact of manifestations of genital infections in different gestational periods on the course of pregnancy and the state of the fetus and newborn. The conducted studies on this issue give reason to talk about the need to review the system of obstetric tactics for these pregnant women, and further improvement of medical measures for antenatal protection of the fetus with this complication of pregnancy.

Fetal endocrine axes mRNA expression levels are related to sex and intrauterine position

BackgroundThe hypothalamic–pituitary–adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females.MethodsWe utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum.ResultsWe found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males’, but in the last trimester of pregnancy, male components were more related to each other than female’s.ConclusionsThis study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development.

Formation of the Mandibular Condylar Cartilage in Human Specimens Between 10 and 15 Weeks of Gestation

Background: The study examines some morphological and histological factors that may contribute to condylar cartilage (CC) formation. The specimens used were consecutive sections obtained from 20 human fetuses ranging in age from 10 to 15 weeks. The vascular canals (VC) emerge in the CC and initiate the process of intramembranous ossification. The mandibular condylar cartilage is crucial for the growth and function of the mandible, and it also contributes to the development of the Temporomandibular joint. Understanding the development of mandibular condylar cartilage throughout the early stages of gestation is essential for detecting congenital craniofacial deformities. Objectives: Examine the stages of MCC development in human samples from fetuses at 10-15 weeks of gestation. Study Design: A descriptive Cross-sectional Study. Place and Duration of Study: Department of Anatomy and Obstetric Nowshera Medical College from 15th Nov 2020 to 1st Jun 2021. The changes in the shape and size of the bones and the processes of bone formation should also be determined. Methods: The current study is descriptive, cross-sectional, and involves post-mortem human fetal specimens aged 10-15 weeks. The specimens were obtained from the Department of Obstetrics of QHAMC after miscarriages and intrauterine deaths. The absence of external and congenital malformations was verified. Light microscopic and histological assessment was done with the aid of H&amp;E-stained sections. Results : Twenty fetal specimens were used in the study, with an average gestation period of 12. 5 weeks (±1. 5 weeks). Histological analysis revealed gradual chondrocyte maturation and the beginning of the ossification process. At ten weeks, MCC was comprised of undifferentiated mesenchymal cells. At twelve weeks, it is possible to observe the differentiation of chondrocytes and early ossification. At 15 weeks, the ossification stages of the CRL were at a superior level with the hypertrophic chondrocytes and mineralized cartilage. The p-values for differences in developmental stages between the gestational ages were less than 0. Hence, the differences were statistically significant. Conclusion: The MCC in human specimens at 10–15 weeks' gestation undergoes considerable morphological transformation and commences the ossification process. Knowledge of these stages is essential in identifying and intervening in congenital craniofacial disorders. The authors recommend that future studies focus on investigating molecular processes that may contribute to the development of MCC. Keywords: Mandibular condylar cartilage, Development, Gestation, Ossification

Red-rumped agouti (Dasyprocta leporina linnaeus, 1758) yolk sac development during the early gestation stage

Red-rumped agouti (Dasyprocta leporina linnaeus, 1758) yolk sac development during the early gestation stage

P-430 The placentation defects are associated with the abnormal proangiogenic signaling of Hofbauer cells driven by advanced maternal age

Abstract Study question Does the abnormality of Hofbauer cells, a subtype of macrophages, in the placental villi cause abnormal placental development in advanced pregnant women? Summary answer Maternal age has a significant impact on the proangiogenic capacity of Hofbauer cells in the placental villi. What is known already Hofbauer cells, a population of macrophages that existed in the placental villi, are known to be related to the transmission of pathogens in the materno-fetal interface. In addition, it has been known that Hofbauer cells can express some cytokines, such as VEGF-A and IL-8, being able to promote angiogenesis. Advanced maternal age has a higher probability to cause placental abnormalities. Whether this is related to alterations in the pro-angiogenic capacity of Hofbauer cells is not clear. Study design, size, duration To investigate the relationship between the angiogenic capacity of Hofbauer cells and maternal age, we compared the difference in strength of proangiogenetic signaling of Hofbauer cells between advanced maternal age and young maternal age in the single cell level, and identified the genes in Hofbauer cells that are most affected by advanced maternal age, which was further validated by immunofluorescence and in vitro tube formation assay. Participants/materials, setting, methods We collected six placental tissues (3 advanced maternal age and 3 young maternal age) across mid- and later-gestational trimesters and performed scRNA-seq, cytometry analysis, and tube formation assay. In addition, we performed immunofluorescence to validate the findings in the scRNA-seq data. Main results and the role of chance We report that the number of macrophages in the placenta of advanced maternal age is significantly lower than in the placenta of younger counterpart, and Hofbauer cell, a fetal-derived macrophage within the placental villi, has obvious down-regulation of proangiogenic signal in advanced maternal age, which is closely associated with the occurrence of placentation defects. Since some key angiogenic factors, such as HIF1A, appear to be more important in the early stages of placental development, placental malformations associated with them may occur more frequently in the early stage of gestation. Limitations, reasons for caution Although we tentatively identified the effect of advanced pregnancy on the angiogenesis-promoting capacity of Hofbauer cells, it is unclear about the dynamic course of angiogenesis signaling of Hofbauer cells throughout the whole gestation. It is necessary to understand the effects of Hofbauer cells on placental development at different gestational trimesters. Wider implications of the findings The investigations of this study into the proangiogenesis of Hofbauer cells are useful to develop potential placental interventions to ameliorate poor birth outcomes. In addition, it lays the foundation for further understanding the underlying molecular mechanism regulating the proangiogenic function of Hofbauer cells in detail. Trial registration number not applicable

P-406 Late paternal effect rooted in sperm DNA double-strand breaks (DSBs) correlates with the likelihood of miscarriage in patients with poor ovarian response

Abstract Study question Can paternal risk factors be minimized and prevented in ICSI procedure? Summary answer The influence of DSBs can be prevented in ICSI cases with normal ovarian response, whereas DSB is exclusively associated with miscarriage in poor ovarian reserve. What is known already Sperm DNA fragmentation (SDF) is intricately linked to male fertility capacity, with a high prevalence affecting 20% of men with unexplained infertility and up to 50% of those with idiopathic infertility. Despite these statistics, the association between paternal DNA damages and clinical outcomes is controversial. Variations in SDF effects may be influenced by female factors associated with maternal DNA repair activity. To elucidate this interrelationship, we assessed SDF effects on diverse ovarian responses using POSEIDON stratification. The goal was to identify potential paternal risk factors for ART as a preventative solution and devising preventative strategies. Study design, size, duration This retrospective study included 323 couples who underwent ICSI cycles at Lee Women’s Hospital. Normal responders (n = 89) were identified based on female age (&amp;lt;35 years) and AMH levels (≥1.2 ng/mL). Patients (n = 234) fulfilling POSEIDON group 1–4 criteria were categorized as poor ovarian response (POR). Clinical outcomes assessed included clinical pregnancy, miscarriage, and live birth rates. Participants/materials, setting, methods Paternal risk factors include male age, semen parameters (CEROS II CASA, Hamilton-Thorne), and two types of SDF evaluation. LensHooke® R10 kit (Bonraybio, Taiwan) was used to detect total SDF (tSDF), which includes single-strand breaks and double-strand breaks (DSBs). LensHooke® R11 kit was specifically used for DSB detection. Kruskal-Wallis test was conducted to compare controls and cases of ART failure. Univariate and multivariate logistic regression analyses were employed to identify potential factors. Main results and the role of chance We sought to evaluate paternal effects during the early gestation stage by comparing parental characteristics in groups with clinical pregnancy and those without pregnancy. No significant differences in paternal indications were observed between the groups. Notably, significantly lower AMH levels and advanced maternal age were prevalent in pregnancy failures across both normal responders and POR cases, highlighting maternal factors’ dominance in these outcomes. When dissecting paternal effects during the later gestation stage, male factors did not show a significant difference between the group with live birth and the group with miscarriage among normal responders. Nevertheless, several paternal pathogenic indications were identified between the groups in POR. Miscarriages were associated with compromised sperm total motility (68% vs. 54.5%, p = 0.01), reduced normal morphology rate (5.5% vs. 2.5%, p = 0.03), and elevated DSB levels (7.5% vs. 18.8%, p = 0.01). Furthermore, multivariate regression analysis identified high DSBs as an exclusive paternal factor in miscarriage risk (Odds ratio: 1.19, 95% confidence interval 1.04–1.36, p = 0.01). In the ROC curve, a DSBs threshold of 19%, based on the R11 technique, offers significant value in predicting miscarriage with an accuracy of 81%. Limitations, reasons for caution The limitations of the current study are single-center trial, and relatively small sample size. Further clinical trials are needed to robustly establish the relationship between DSB and miscarriage. Wider implications of the findings The impact of DSBs is overlooked in normal responders but not in POR due to different levels of maternal DNA repair activity. These results advocates for (1) the necessity of DSBs (R11) assessment for POR, and (2) egg donation as a potential strategy for couples facing high DSBs and POR. Trial registration number CS2-20012

Reproductive and fetal toxicity studies of histamine H3 receptor antagonist DL76 used in mice to prevent maximal electroshock-induced seizure.

Introduction: Brain histamine is considered an endogenous anticonvulsant and histamine H1 receptor. H1R antagonists have, in earlier studies, been found to induce convulsions. Moreover, research during the last twodecades has provided more information concerning the anticonvulsant activities of histamine H3R (H3R) antagonists investigated in a variety of animal epilepsy models. Methods: Therefore, the in vivo anticonvulsant effect of the H3R antagonist DL76, with proven high in vitro affinity, in vitro selectivity profile, and high in vivo antagonist potency in mice against maximal electroshock (MES)-induced seizures in mice, was assessed. Valproic acid (VPA) was used as a reference antiepileptic drug (AED). In addition, DL76 was tested for its reproductive and fetal toxicity in the same animal species. Results and discussion: Our observations showed that acute systemic administration (intraperitoneal; i.p.) of DL76 (7.5mg/kg, 15mg/kg, 30mg/kg, and 60mg/kg, i.p.) provided significant and dose-dependent protection against MES-induced seizures in female and male mice. Moreover, the DL76-provided protective effects were comparable to those offered by the VPA and were reversed when animals were co-administered the CNS-penetrant selective H3R agonist R-(α)-methylhistamine (RAM, 10mg/kg, i.p.). Furthermore, the administration of single (7.5mg/kg, 15mg/kg, 30mg/kg, or 60mg/kg, i.p.) or multiple doses (3 × 15mg/kg, i.p.) of H3R antagonist DL76 on gestation days (GD) 8 or 13 failed to affect the maternal body weight of mice when compared with the control mice group. No significant alterations were detected in the average number of implantations and resorptions between the control and DL76-treated groups at the early stages of gestation and the organogenesis period. In addition, no significant differences in the occurrence of skeletal abnormalities, urogenital abnormalities, exencephaly, exomphalos, facial clefts, and caudal malformations were observed. The only significant abnormalities witnessed in the treated groups of mice were in the length of long bones and body length. In conclusion, the novel H3R antagonist DL76 protected test animals against MES-induced seizures and had a low incidence of reproductive and fetal malformation with decreased long bone lengths in vivo, signifying the potential therapeutic value of H3R antagonist DL76 for future preclinical as well as clinical development for use in the management of epilepsy.

O13 Benchmarking a human pluripotent stem cell-derived hair-bearing skin organoid model to prenatal skin

Abstract Introduction and aims Molecular regulation of mammalian skin development has been largely derived from murine studies. The lack of human studies stems primarily from the difficulties in prenatal human skin access. There is an important need to study human prenatal skin owing to the notable differences between human and mouse skin and the paucity of mechanistic understanding of congenital skin disorders. Methods We assembled the first comprehensive multiomic reference atlas of prenatal human skin (21 samples from 7 to 16 postconception weeks), combining single-cell (235 201 cells) and spatial transcriptomic data. We followed 84 skin organoids (SkOs) using single-cell analysis over a 5-month culture period and characterized the spatial organization of the skin in mature SkOs. Prenatal skin, SkO and any relevant pre-existing single-cell RNA-Seq datasets were integrated into the analysis. Cell–cell interactions and cell-lineage determination were explored using CellPhoneDB and trajectory inferences. We evaluated the differentiation trajectory alignment between prenatal skin and SkO using the Genes2Genes analysis. Results Our findings reveal predicted factors regulating the epithelial–mesenchymal crosstalk during human hair follicle formation; progressive expression of scar-promoting genes in later gestation, potentially contributing to scarless healing properties of human prenatal skin observed during the early stages of gestation and expression of genes causing genetic skin disorders in the same cell types in prenatal human skin and SkO. We also found that SkOs morphologically recapitulate human skin development from early (periderm formation and shedding) to late (cornification and hair follicle formation) stages. We also demonstrated that SkO and prenatal skin mesenchyme differentiation into hair follicle dermal condensate and dermal papilla is highly conserved at the cellular and molecular level. Conclusions SkOs faithfully recapitulate human prenatal skin development and are a valuable model for mechanistic studies on skin development including hair follicle biology and congenital skin disorders.

Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Relationship between plasma anti-Müllerian hormone concentrations in female Holstein calves immediately after birth and milk yield and composition in dams during early to mid gestation

The energy status of dams during the early stages of gestation may affect ovarian reserves. It was hypothesized that greater milk yield and composition during the early stages of gestation may suppress the number of primordial follicles in the fetuses of dairy cattle. This study aimed to evaluate the anti-Müllerian hormone (AMH), used as an indicator of ovarian reserves, in female Holstein calves immediately after birth. It also examined the relationship between AMH concentrations and the milk yield and composition of dams during early pregnancy. A total of 85 female Holstein calves (born to first-calving cows [nulliparous heifers], n = 31; second-calving [primiparous] cows, n = 22; and third- or subsequent-calving [multiparous] cows, n = 32) were examined. Blood samples were collected from the female calves after birth and before the first colostrum feeding for the analysis of plasma AMH concentrations. Data on daily milk yield and monthly milk composition during the first to sixth month of pregnancy were additionally collected from milking dams. The plasma AMH concentrations ranged from 0.106 to 1,542.3 pg/mL, with an average of 291.6 ± 30.5 pg/mL. No significant differences were observed among the plasma AMH concentrations in female calves born from nulliparous heifers, primiparous cows, or multiparous cows. Primiparous cows exhibited numerous negative correlations between the plasma AMH concentrations of their female calves immediately after birth and the daily milk yield and milk composition from the first to the fourth month of pregnancy; however, no correlation was observed in multiparous cows. Overall, large individual variations were observed in the plasma AMH concentrations immediately after birth. Both milk yield and the amount of milk components strongly influenced plasma AMH concentrations in calves immediately after birth in primiparous cows in the growth phase. These factors, conversely, did not affect the plasma AMH concentrations of calves in multiparous cows. The results of this study suggest that high-producing pregnant primiparous cows devote more energy to their growth and lactation, potentially compromising the reproductive potential of their offspring. Thus, improving the feeding management of primiparous cows with the goal of increasing the fertility of their progeny will help high-yielding dairy cows reproduce more successfully.

Features of the state of extraembryonic structures in miscarriage early terms of pregnancy

Background. Despite the modern achievements of medicine, miscarriage remains the main problem of obstetrics and gynecology science and practice. Purpose – to assess the features of the state of extraembryonic structures in case of miscarriage in the early stages of gestation. Materials and Methods. Under observation were 32 patients (main group) with a verified threat of pregnancy termination with bleeding in the embryonic period of gestation (up to 10 weeks) and 20 women (control group) with a physiological course of early pregnancy. The exclusion criteria from the study were patients with induced pregnancy, multiple pregnancies, anomalies of the development of female genital organs. All patients underwent a standard clinical and laboratory examination. During the ultrasound examination, both the state of the embryo and the state of extraembryonic structures were evaluated: the volume of the fertilized egg (V f/e), the average internal diameter of the yolk sac, the nature of vascularization of the corpus luteum, the state of hemodynamics in the myometrium. During transvaginal ultrasound, the chorionic volume (Vc) was calculated and its vascularization index (VI) was evaluated using a special three-dimensional VOCAL program. Results. Analysis of embryo biometrics in the studied groups did not reveal any significant difference. When assessing the state of extra-embryonic structures, we found that the volume of the fertilized egg and the average internal diameter of the yolk sac in women with miscarriage in the embryonic period of gestation was significantly lower. The volume of the corpus luteum of the ovary in the main group was equal to 3.0±0.3 cm3 in the control group – 5.3±0.61 cm3 , (p &lt; 0.05). Vascularization of the corpus luteum in patients with bleeding in early pregnancy was also reduced. In patients with threatened termination of pregnancy with bleeding, Vc was 32.5±2.08 cm3 in control 71.6±2.4 cm3 . The vascularization index of the chorion in pregnant women of the main group was equal to 9.5±1.2, while in women with a physiological course of gestation it was 19.1±1.7 (p&lt;0.05). When evaluating the hemodynamics in the myometrium, it was also established that the resistance index in the uterine and spiral arteries in the patients of the main group was significantly higher compared to the pregnant women of the control group. Conclusions. When there is a threat of pregnancy termination with bleeding in the embryonic period of intrauterine development of the child, significant changes occur in extraembryonic structures. A decrease in the volume of the fertilized egg, the average internal diameter of the yolk sac, blood flow disorders in the corpus luteum and myometrium, a decrease in vascularization of the chorion and its hypoplasia create a high risk of developing placental dysfunction and worsen the prognosis of pregnancy.

Differential Development of the Chordae Tendineae and Anterior Leaflet of the Bovine Mitral Valve.

There is increasing evidence that some adult mitral valve pathologies may have developmental origins involving errors in cell signaling and protein deposition during valvulogenesis. While early and late gestational stages are well-documented in zebrafish, chicks, and small mammalian models, longitudinal studies in large mammals with a similar gestational period to humans are lacking. Further, the mechanism of chordae tendineae formation and multiplication remains unclear. The current study presents a comprehensive examination of mitral anterior leaflet and chordae tendineae development in a bovine model (a large mammal with the same gestational period as humans). Remarkably distinct from small mammals, bovine development displayed early branched chordae, with increasing attachments only until birth, while the anterior leaflet grew both during gestation and postnatally. Chordae also exhibited accelerated collagen deposition, maturation, and crimp development during gestation. These findings suggest that the bovine anterior leaflet and chordae tendineae possess unique processes of development despite being a continuous collagenous structure and could provide greater insight into human valve development.

Prevalence, Pattern and Outcome of Congenital Anomalies in Patients Admitted at a Tertiary Level Hospital in Bangladesh

Congenital anomalies are a major public health concern globally, contributing significantly to perinatal and neonatal mortality. Understanding their prevalence, patterns, and outcomes are essential for effective healthcare planning and interventions. This cross-sectional observational study aimed to investigate the distribution and immediate outcomes of congenital anomalies among infants delivered at Bangabandhu Sheikh Mujib Medical College Hospital, Faridpur, Bangladesh. Study population comprised admitted pregnant mothers who delivered infants with congenital anomalies from January to December 2022. Data were collected from medical records, including parity, gestational age at delivery, mode of delivery and outcomes of congenital anomalies. Total 3461 deliveries occurred during this period, of which 88 had congenital anomalies with a prevalence of 2.54%. Among the 88 infants with congenital anomalies, the most prevalent anomalies were Anencephaly and Hydrocephalus, affecting the central nervous system. Anencephaly had a 100% mortality rate, emphasizing its severity and poor prognosis. Anencephaly was more common in infants delivered between 12 to 28 weeks. Early gestational stages play critical role in its pathogenesis. Hydrocephalus showed a relatively higher proportion of live births. Vaginal delivery was the predominant mode of delivery for most congenital anomalies. Public health efforts targeting early detection, appropriate care and support for affected families can potentially reduce the impact of congenital anomalies on maternal and neonatal health. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):27-31