Fetal Morphology Research Articles

The Effect of Giving Red-fleshed Watermelon Juice (Citrullus lanatus (Thunb.)) on Pregnant White Mice (Mus Musculus) Exposed by Monosodium Glutamate (MSG) Orally on the Number and Morphology of Fetus

Introduction: Infertility can occur due to the presence of free radicals. One of the most popular of free radical is monosodium glutamate. Free radicals from monosodium glutamate can be prevented by antioxidant compounds. Red-fleshed-fleshed watermelon is a fruit that contains antioxidant compound such as lycopene. Aim: This research was conducted to see the effect of red-fleshed-fleshed watermelon juice on the fetus including number, morphology, visual abnormalities and body weight of pregnant white mice exposed to monosodium glutamate solution orally. Total of 25 female white mice aged around 2-3 months were used as test animals. Methods: Pregnant white mice were divided into 5 test groups. Group I and II served as negative controls (whithout treatment) and positive controls (exposed to monosodium glutamate solution orally at dose of 1g/kgBW). Group III was given a solution of monosodium glutamate orally at dose of 1 g/KgBW added red-fleshed-fleshed watermelon juice at dose of 1.4 g/kgBW. Group IV was given solution of monosodium glutamate orally at dose of 1 g/KgBW added red-fleshed-fleshed watermelon juice at dose of 4.2 g/kgBW. The research data were processed using the one-way ANNOVA test. Results: The result showed that mice body weight, fetal number and morphology (body weight, body length, tail length, and head diameter) did not significantly influence (p>0.05). However, it significantly affected the weight gain of mice during pregnancy. However, it significantly affected the weight gain of mice during pregnancy day 6 to day 17 of pregnancy (p<0.05) and found abnormalities in the fetus such as low birth weight (LBW) and haemorrhage in group II and III. Conclusion: It can be concluded that watermelon juice at dose of 2.8 g/kgBW and 4.2 g/kgBW are effective in ward offfree radicals from monosodium glutamate orally at dose of 1 g/kgBW.

Fetal ECG signal processing and identification of hypoxic pregnancy conditions in-utero.

The fetal heart rate (fHR) variability and fetal electrocardiogram (fECG) are considered the most important sources of information about fetal wellbeing. Non-invasive fetal monitoring and analysis of fECG are paramount for clinical trials. They enable examining the fetal health status and detecting the heart rate changes associated with insufficient oxygenation to cut the likelihood of hypoxic fetal injury. Despite the fact that significant advances have been achieved in electrocardiography and adult ECG signal processing, the analysis of fECG is still in its infancy. Due to accurate fetal morphology extraction techniques have not been properly developed, many areas require particular attention on the way of fully understanding the changes in variability in the fetus and implementation of the non-invasive techniques suitable for remote home care which is increasingly in demand for high-risk pregnancy monitoring. In this paper, we introduce an integrated approach for fECG signal extraction and processing based on various methods for fetal welfare investigation and hypoxia risk estimation. To the best of our knowledge, this is the first attempt to introduce the auto-generated risk scoring in fECG to achieve early warning on fetus' safety and provide the physician with additional information about the possible fetal complications. The proposed method includes the following stages: fECG extraction, fHR and fetal heart rate variability (fHRV) calculation, hypoxia index (HI) evaluation and risk estimation. The extracted signals were examined by assessing Signal to Noise Ratio (SNR) and mean square error (MSE) values. The results obtained demonstrated great potential, but more profound research and validation, as well as a consistent clinical study, are needed before implementation into the hospital and at-home monitoring.

Influence of birth weight on fetal cardiac indices at 35–37 weeks' gestation

Echocardiographic studies have reported that fetuses with low birth weight, compared to those with normal birth weight, have globular hearts and reduced cardiac function. Dichotomizing continuous variables, such as birth weight, may be helpful in describing pathology in small studies but can prevent us from identifying physiological responses in relation to change in size. The aim of this study was to explore associations between fetal cardiac morphology and function and birth weight, as a continuous variable, as well as uterine artery (UtA) pulsatility index (PI), as an indirect measure of placental perfusion, and the cerebroplacental ratio (CPR), as an indirect measure of fetal oxygenation. This was a prospective study of 1498 women with singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Pregnancies complicated by pregestational or gestational diabetes mellitus, chronic hypertension, pregnancy-induced hypertension or pre-eclampsia were excluded from the analysis. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricles. The morphology of the fetal heart was assessed by calculating the right and left sphericity indices. In addition, the PI of the UtA, umbilical artery (UA) and fetal middle cerebral artery (MCA) was determined and the CPR was calculated by dividing MCA-PI by UA-PI. Multiple linear regression models were used to assess determinants of fetal echocardiographic parameters. The study population included 146 (9.7%) small-for-gestational-age (SGA) fetuses with birth weight < 10th percentile and 68 (4.5%) with fetal growth restriction (FGR). In the SGA and FGR groups, compared to the non-SGA and non-FGR fetuses, respectively, there was a more globular right ventricle and reduced left and right ventricular systolic function, and, from the left ventricular diastolic functional indices, the E/A ratio was increased. There was a linear association of right ventricular sphericity index, indices of left and right ventricular systolic function and E/A ratio with birth-weight Z-score. There were no significant associations between cardiac morphological and functional indices and UtA-PI Z-score or CPR Z-score. This screening study at 35-37 weeks' gestation has demonstrated that birth weight is a determinant of fetal cardiac morphology and function but UtA-PI and CPR, as indirect measures of placental perfusion and fetal oxygenation, are not. This suggests that the differences in fetal cardiac indices between small and appropriately grown fetuses may be part of a normal physiological response to change in fetal size rather than part of a pathological adaptation to abnormal placental perfusion and fetal oxygenation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

SCAP knockout in SM22α-Cre mice induces defective angiogenesis in the placental labyrinth

The placental labyrinth is important for the exchange of nutrients and gases between the mother and the embryo in mice. This interface contains cells of both trophoblast and allantoic mesodermal origin that together produce maternal blood sinuses and placental blood vessels. However, the molecular mechanisms that take place during process of placental labyrinth development, especially concerning fetal capillaries, are not well understood. SREBP cleavage-activating protein (SCAP), a membrane protein, is required for the synthesis of fatty acids and cholesterol. Recently, when we crossed the offspring of the cross between smooth muscle 22 alpha (SM22α)- Cre recombinase (Cre) mice and SCAPloxp/loxp mice to research the function of SCAP in vascular smooth muscle cells (VSMCs) during certain pathological processes, we found that there were no resultant SM22α-Cre-specific SCAP knockout (KO) pups (SM22α-Cre+SCAPflox/flox; hereafter referred to as SCAP KO). Through anatomic studies of these embryos and placentas, we found that SCAP KO resulted in defective placental vessels and abnormal fetal morphology. Further immunohistochemical and immunocytochemical analyses suggested that SCAP is knocked out in the pericytes of the placental labyrinth. Compared to wildtype mice, SCAP KO placentas had abnormal vasculature in the labyrinth and lower levels of angiogenesis. By using RNA-seq and western blotting, we found that the expression of some genes and proteins in SCAP KO placentas was changed, including those related to pericyte/endothelial interactions genes and angiogenesis. Our results suggest that the proper organizational structure of the placental labyrinth depends on SCAP expression in pericytes.

Abstract 17061: Impact of Maternal Anxiety on In Vivo Placental Development in Fetuses With Congenital Heart Disease

Introduction: Studies have shown that maternal stress and anxiety during pregnancy have been associated with a higher incidence of preterm birth and low birth weight. However, the relationship between prenatal maternal mental distress and placental development in fetuses with congenital heart disease (CHD) is unknown. Hypothesis: We tested the hypothesis that elevated maternal anxiety is associated with altered placental morphology in fetuses with CHD. Methods: A total of 141 pregnant women were recruited prospectively (control: 91; two-ventricle/2V CHD: 29; single-ventricle/SV CHD: 21), in which 228 fetal MR scans were performed (gestational age: 31.8±4.5 weeks). Single shot fast spin echo T2-weighted images were acquired on a 1.5 Tesla GE MRI scanner. Placenta tissue was manually segmented, and slice-to-volume registration was used for motion correction and 3D reconstruction. Six placental features were calculated: volume, thickness, elongation, surface area, mean diameter, and umbilical cord centricity. We completed the Spielberger State (SSAI) and Trait (SSAI) Anxiety Inventory at each study visit. Linear mixed models were utilized to analyze the placental features predicted by maternal anxiety. Results: Placental volume, surface area, and mean diameter were decreased with elevated SSAI in 2V CHD fetuses, while volume and cord centricity were increased with higher SSAI in SV CHD fetuses. Lower cord centricity was associated with elevated STAI in 2V CHD fetuses, and elongation was positively associated with STAI in SV CHD fetuses. There were no associations between anxiety measures and placental features in control fetuses. Conclusions: We report for the first time that elevated prenatal maternal anxiety is associated with altered in vivo placental structures in pregnancies complicated by fetal CHD. Our data suggest that disturbances in placental structure vary based on the type of fetal CHD (SV vs. 2V) in the setting of elevated prenatal maternal anxiety.

Hematopoietic Jagged1 Is Required for the Transition of Hematopoietic Stem Cells from the Fetal Liver to the Adult Bone Marrow Niche

Notch signaling is known to play important roles in hematopoietic development and differentiation. Notch1 is required for emergence of the definitive hematopoietic stem cells (HSCs) from the hemogenic endothelium, and we have previously shown that Notch signaling is essential for survival and function of HSCs in the fetal liver. Activation of canonical Notch signaling requires direct cellular contact; thus, the identity of the ligand and the ligand-presenting cell during hematopoietic development would provide valuable information of the Notch signaling mechanism in HSCs as well as the identity of key niche cells that drive the expansion and cell fate decisions of embryonic HSCs. In the present study, we have taken a comprehensive approach to determine the ligands and cells that initiate Notch signaling in the mouse fetal liver. To this end, we have performed single-cell PCR analysis for all Notch signaling proteins in E14.5 fetal HSCs and compared the findings to the adult bone marrow HSCs. We also have analyzed fetal liver endothelial cells for surface expression of all Notch ligands. We determined that Jagged1 (Jag1) is highly expressed in both endothelial cells as well as in fetal HSCs but not adult HSCs. We have performed conditional loss-of-function analysis of Jag1 in fetal endothelial cells using inducible Ve-cadherinCreERT2 as well as in fetal hematopoietic lineages using constitutive VavCre. Our results indicate that while loss of endothelial Jag1 has severe effects in embryonic vascular development, loss of hematopoietic Jag1 allows for normal fetal morphology, yet severely impedes the functional ability of fetal liver HSCs to expand and differentiate both in vitro and in vivo. Fetal to adult transplantation of VavCre+Jag1f/f HSCs indicated a defect in reconstitution potential of fetal HSCs that lack Jag1 expression. Our findings indicate that hematopoietic Jag1 is essential for maturation of HSCs in the fetal liver and for homing and reconstitution potential of HSCs into the post-natal bone marrow microenvironment. Disclosures No relevant conflicts of interest to declare.

The impact of maternal diabetes on fetal left atrial size and function

Abstract Introduction The developmental impact of maternal diabetes on the fetal left atrium (LA) is unclear. Purpose To determine if maternal diabetes mellitus (DM) impacts fetal LA size and function (fetal LA strain (LAS)). Methods We evaluated LA area (LAA) and LAS on fetuses of diabetic and control mothers who attended a mandated 24 week fetal morphology scan. Participants were excluded from the study if: there was a history of pre-eclampsia or if the fetus did not have adequate images for LAS analysis We used fetal cardiac 4-chamber view for analysis. A region of interest was drawn along the LA endocardial border for tracking and was used for assessment of maximum LAA. Baseline variables were compared using Student t test or Mann-Whitney U test and are presented as Mean ± Standard Deviation or Median (Interquartile range (IQR)). Body mass index (BMI), maternal age, gestational age, fetal heart rate (FHR), smoking status, estimated fetal weight (EFW) and Maternal DM were analysed in univariate and multivariate models with respect to LAA and LAS. Results 160 pregnant women (50 controls, 110 diabetics) were scanned. 9 were excluded due to poor image quality, resulting in 104 mothers with diabetes (T1DM 9, T2DM 8, and gestational DM 87) and 47 controls without diabetes. The mothers were well matched for age, blood pressure, smoking prevalence and gestational age. The diabetic mothers had a significantly higher BMI: Median (IQR) ((30.4 kg/m2 (25.1–34.8) vs 20.8 kg/m2 (21.4–27.4), p&amp;lt;0.001) and had higher weight (77 kg (65–93) vs 64 kg (62–68), p&amp;lt;0.001). FHR was higher in fetuses of diabetic mothers (147±10 vs 144±8, p 0.04). Maternal DM resulted in larger LAA 1.68 cm2±0.39 cm2 vs 1.56 cm2±0.36 cm2; p=0. 08, however the result was not significant. The LAS was significantly lower in fetuses with maternal DM compared to fetuses of controls: 28.8% ± 8.8% vs 32.3% ± 9.2%; p 0.033. On multivariate analysis (Table 1), the predictors of LAS were Maternal DM and FHR and predictors of LAA were EFW and Maternal DM. Conclusions Maternal diabetes modulates both LA size and LA function. The association between LA function and FHR may provide an explanation for fetal tachycardia in Maternal DM. Fetal left atrial strain Funding Acknowledgement Type of funding source: None

Impact of Maternal Exposure to Wood Smoke Pollution on Fetal Lung Morphology in a Rat Model

Impact of Maternal Exposure to Wood Smoke Pollution on Fetal Lung Morphology in a Rat Model

VP51.01: Low‐lying placenta at the fetal morphology ultrasound scan and postpartum hemorrhage: a retrospective case controlled study

VP51.01: Low‐lying placenta at the fetal morphology ultrasound scan and postpartum hemorrhage: a retrospective case controlled study

Effects of nifedipine on fetal cardiac function in preterm labor.

Objectives To evaluate the effects of nifedipine treatment on fetal hemodynamics and cardiac function during preterm labor. This prospective study assessed several quantitative parameters of fetal cardiac circulation and function, and found no significant changes at 48h after nifedipine treatment. These findings suggest that tocolytic nifedipine may be safe for fetuses. It supports clinicians to use nifedipine treatment for tocolysis without any cardiac effect on the fetus. Methods A prospective cohort study was conducted at a tertiary hospital between January 2016 and October 2017. A total of 45 pregnant women who required nifedipine for preterm labor were included in this study. Fetal Doppler ultrasound was performed and fetal systolic and diastolic function was measured prior to, and 48h after, the first nifedipine treatment. Conventional Doppler parameters were used to evaluate fetal heart function and hemodynamic changes. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and the sphericity index were also evaluated to assess changes in fetal cardiac morphology. Results No significant changes in fetal Doppler parameters were observed following nifedipine tocolysis. There was no significant difference in the fetal cardiac function parameters of both ventricles before vs. after nifedipine treatment. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, and sphericity index values were unchanged following nifedipine treatment. Conclusions Oral administration of nifedipine did not to alter fetal cardiac function or morphology. Fetal cardiac parameters and various Doppler indices were unchanged following nifedipine treatment. Maternal nifedipine treatment does not appear to have any significant effect on fetal cardiac function.

The Melatonin and Enriched Environment Ameliorated Low Protein-Induced Intrauterine Growth Retardation by IGF-1 And mtor Signaling Pathway and Autophagy Inhibition in Rats.

Sprague-Dawley rats were randomly allocated to 3 groups: control (C), model (M) and EE+MEL group. Animals were housed in an enriched environment (EE+MEL group) or remained in a standard environment (C group, M group). IUGR rat model was built by feeding a low protein diet during pregnancy. MEL was administered by gavaging. At day 1 post-birth, the baseline characteristics and serum biochemical parameters, morphology of liver and small intestine, enzyme activities, and mRNA expression levels of fetal rats were determined. The autophagy marker LC3 and Beclin1 were determined by western blot analysis. EE+MEL markedly improved the baseline characteristics, hepatic and intestinal morphology of IUGR fetuses. In addition, the lactase activities in the fetal intestine were markedly increased by the EE+MEL. The levels of serum somatostatin (SST), Growth hormone (GH), GH releasing hormone (GHRH), Insulin-like Growth Factor 1 (IGF-1), triiodothyronine (T3), and tetraiodothyronine (T4) were found to be recovered by EE+MEL. In addition, the EE+MEL significantly ameliorated the mRNA expression of SST, GHRH, and GHRH receptor (GHRHR), GH, GHR, IGF-1, and IGF-1 receptor (IGF1R), IGF binding protein-1 (IGFBP1), mammalian target of rapamycin (mTOR), S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) in fetuses. In IUGR fetal livers, LC3 and Beclin1 were found to be increased at birth, while LC3 and Beclin1 were observed to be significantly decreased in the EE+MEL group. EE+MEL could improve fetal rats' baseline characteristics, serum biochemical parameters, birth weight, intestinal and hepatic morphology and enzyme activities. These effects could be explained by the activation of the IGF-1/IGFBP1 and IGF-1/mTOR/S6K1/4EBP1 signaling pathway and autophagy inhibition.

Efeitos do uso dos anti-inflamatórios não esteroides na prevalência de malformações estruturais fetais

Objetivo: Avaliar o uso dos anti-inflamatórios não esteroidais (AINEs) na prevalência de malformações congênitas (MC) estruturais. Métodos: Estudo do tipo caso-controle, realizado em um hospital público referência em medicina fetal. Foi aplicado um questionário para avaliar os fatores sociodemográficos e obstétricos. A avaliação da morfologia fetal foi realizada através da avaliação ultrassonográfica. Resultados: Das 282 gestantes avaliadas, 28,72% (81/282) relataram uso de anti-inflamatórios durante a gravidez, sendo 75,1% (n = 60) do grupo caso e 25,9% (n = 21) do grupo controle. Entre os anti-inflamatórios, os mais utilizados foram nimesulida (17,38%; n = 49), diclofenaco (10,99%; n = 31) e ibuprofeno (3,19%; n = 9). O uso de AINEs em geral e específico (nimesulida, diclofenaco, ibuprofeno) não apresentou diferença entre os grupos. No entanto, foi observado o maior uso de ibuprofeno no grupo caso (4,46%; n = 9) vs controle (0%; n = 0) com OR = 7,904, p = 0,05. O uso de AINEs foi maior em gestantes que apresentavam fetos com MC da face (55,6%), parede abdominal (38,10%) e do sistema nervoso central (SNC) (30,30%). Conclusão: Embora não tenham sido observadas diferenças entre os grupos, o uso de AINES foi considerável em pacientes que tiveram feto com malformações fetais da face, parede abdominal e SNC. Devido à alta frequência de algumas malformações, especialmente as da face, deve-se ter o cuidado com a indicação e principalmente com a automedicação dessa classe medicamentosa durante a gravidez.

Evaluation of Leaf Extracts of Costus afer on Foetal Morphology and Cerebral Cortex Using Rat Model

Evaluation of Leaf Extracts of Costus afer on Foetal Morphology and Cerebral Cortex Using Rat Model

Circulating catecholamines partially regulate T-wave morphology but not heart rate variability during repeated umbilical cord occlusions in fetal sheep.

Fetal heart rate (FHR) variability (FHRV) and ST segment morphology are potential clinical indices of fetal well-being during labor. β-Adrenergic stimulation by circulating catecholamines has been hypothesized to contribute to both FHRV and ST segment morphology during labor, but this has not been tested during brief repeated fetal hypoxemia that is characteristic of labor. Near-term fetal sheep (0.85 gestation) received propranolol (β-adrenergic blockade; n = 10) or saline (n = 7) 30 min before being exposed to three 2-min complete umbilical cord occlusions (UCOs) separated by 3-min reperfusions. T/QRS ratio was calculated throughout UCOs and reperfusion periods, and measures of FHRV (RMSSD, SDNN, and STV) were calculated between UCOs. During the baseline period, before the start of UCOs, propranolol was associated with reduced FHR, SDNN, and STV but did not affect RMSSD or T/QRS ratio. UCOs were associated with rapid FHR decelerations and increased T/QRS ratio; propranolol significantly reduced FHR during UCOs and was associated with a slower rise in T/QRS ratio during the first UCOs, without affecting the maximal rise or T/QRS ratio during the second and third UCO. Between UCOs propranolol reduced FHR and T/QRS ratio but did not affect any measure of FHRV. These data demonstrate that circulating catecholamines do not contribute to FHRV during labor-like hypoxemia. Furthermore, circulating catecholamines did not contribute to the major rise in T/QRS ratio during labor-like hypoxemia but may regulate T/QRS ratio between brief hypoxemia.

2252-PUB: Fetal Cardiac Evaluation by Ultrasound to Assess Pregnancies Complicated by Maternal Diabetes

Objectives: To evaluate fetal and neonatal cardiac morphology by echocardiography in pregnancies complicated by diabetes compared to normal healthy controls using ultrasound. Methods: Fetal echocardiography was performed in 121 women with uncomplicated singleton pregnancies and 50 women with diabetes in pregnancy. The women underwent ultrasound scans every four weeks from enrolment (between 18-28 weeks gestational age) until delivery. Neonatal echocardiography was performed on the offspring. M-mode assessment was used to assess interventricular septal (IVS) thickness, left ventricle diastolic dimensions (LVED), fractional shortening (FS), tricuspid annular plane systolic excursion (TAPSE) and mitral annular plane systolic excursion (MAPSE). Results: There were differences in IVS thickness, LVED, FS and TAPSE values between women with uncomplicated pregnancies and women with diabetes in pregnancy. These differences persisted into the neonatal period. Conclusion: M-mode is a simple ultrasound technique to assess fetal cardiac function. Maternal diabetes was associated with increased IVS thickness, and reduction in TAPSE and FS measures. Prognostic implications of these findings may be useful in assessing pregnancies complicated by maternal diabetes in addition to current ultrasound assessment of fetal size and Doppler studies of fetal vessels. Disclosure A. Lee-Tannock: None. K. Hay: None. S. Kumar: None. Funding Mater Health Services; Australasian Society for Ultrasound in Medicine

Chemerin Level as a Marker in Preeclampsia and its Relation to the Disease Severity and Neonatal Outcome

Aim of study: To detect serum chemerin level in patient with preeclampsia and evaluate the association between maternal serum chemerin, disease severity and neonatal outcome. Patients and Method: A case control study included 100 pregnant women with singleton pregnancy, gestational age of 20 weeks or more, normal fetal morphology, and absence of concomitant diseases, who were collected from inpatient during delivery was conducted in the Department of Obstetrics and Gynecology at Al-Yarmouk Teaching Hospital during the period from 1st of June 2018 till end of May 2019. They were divided into three groups (control, mild preeclampsia, and severe preeclampsia). Patients with history of chronic hypertension, diabetes mellitus, cardiovascular disease, neurological disorder, renal impairment, or premature rapture of membrane were excluded from this study. blood sample was taken from all patients and sent for human chemerin assay. After delivery, birthweight of baby, APGAR scores at one and five mints, neonatal intensive care unit and adult intensive care unit admission, and hospitalization time were also noted. Results: There were no statistically significant differences between the study groups in age, BMI level, and parity. Chemerin level was significantly elevated in patients with severe preeclampsia (435.06 ng/ml) and mild preeclampsia (227.49 ng/ml) than that in non-preeclamptic patients (202.6 ng/ml). It was negatively correlated with each of gestational age, birth weight, Apgar score at one and five minutes. While it was positively correlated with admission’s duration. Serum chemerin &gt; 228.5 ng/ml is predictive for diagnosis of preeclampsia and level &gt; 380.9 ng/ml is indicator for severe preeclampsia. Conclusion: Chemerin may play a role in the pathogenesis of preeclampsia as maternal serum chemerin level was significantly higher in patients with preeclampsia

Secnidazole, an Approved Single Dose Drug for Bacterial Vaginosis, Does Not Cause Reproductive Toxicity in Animals [16A

INTRODUCTION: Single-dose oral secnidazole 2 g, has recently been approved in the US for treatment of bacterial vaginosis (BV) in adult women. BV is associated with an increased risk of several pathological gynecological conditions as well as major adverse outcomes during pregnancy, where it is associated with a two-fold increased risk of preterm birth and a six-fold increased risk of miscarriage. In order to inform patient labeling, reproductive toxicology studies have been conducted. METHODS: A complete reproductive toxicology program required for patient labeling was conducted. Rats and rabbits were fed varying doses of secnidazole, 0 to 1000 mg/kg/day and 0 to 100 mg/kg/day, respectively, leading up to and throughout gestation. Maternal examinations included clinical observations and survival, food consumption, and parturition. Data obtained from the first-generation (F1) pups included viability, body weight, neurobehavioral and reproductive function. Data including clinical signs, survival and body weights were also obtained for the second generation pups derived from F1 offspring. Adverse events associated secnidazole were measured. RESULTS: Secnidazole showed no reproductive toxicity in animal models. There was no effect on weight, growth, and food consumption for animals administered secnidazole, up to 300 mg/kg/day. There were no effects on survival, intrauterine growth, or external fetal morphology at any dose. CONCLUSION: There was no evidence of secnidazole toxicity in fertility and pre- and postnatal reproductive toxicology. In addition, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose.

Impact of Reduced ASIC2a on Cortical Thickness, Microglia Density, and Brain Water Content in E18.5 Fetuses

Acid‐sensing Ion Channels (ASICs) are ligand‐gated cation channels that respond to acidic stimuli. ASIC2 is widely expressed in neurons of the central and peripheral nervous system as well as on microglia. Although ASIC2 plays a role in cell migration, their role in brain development is not fully known. We tested the hypothesis that reduction or absence of ASIC2a contributes to changes in microglia density, cortical thickness, and brain water content during development. Brains were collected from ASIC2a wild type (WT, n=6), heterozygous (HET, n=4), and homozygous (HOMO, n=3) fetuses at E18.5. We used hematoxylin &amp; eosin (H&amp;E) staining for cortical thickness measurements, immunofluorescence staining using ionized calcium‐binding adapter molecule (Iba‐1) to measure microglia density, and wet weight to dry weight ratio for brain water content. Reduction of ASIC2a had no impact on cortical thickness (WT=499±21, HET=509±7, and HOMO=478±21 μm; p=0.60) or microglia density in the subventricular zone near the lateral ventricle (WT=22±2, HET=18±2, and HOMO=24±3; p=0.34) at E18.5. Interestingly, microglia morphology in HET fetuses were different compared to WT and HOMO mice with thinner and longer processes. Brain water content increased in HOMO mice (88.2±0.7%) compared to WT (86.5±0.3%, p&lt;0.01) and HET (86.8±0.2%, p=0.02) fetuses. Our results indicate that while reduced ASIC2a does not contribute to changes in microglia density or cortical thickness in E18.5 mouse fetuses, reduced ASIC2a induces morphological changes in microglia and ASIC2 knockout increases brain water content at E18.5. Increased brain water content could be an indicator of hydrocephalus. In ongoing studies, we are determining whether reduced ASIC2a mediates structural and functional impairments in the neurovasculature of the maternal and developing brain.Support or Funding InformationNIH Grants: R00HL129192, R00HL129192‐S1

Disruption of fertility, placenta, pregnancy outcome, and multigenerational inheritance of hepatic steatosis by organotin exposure from contaminated seafood in rats

Early life exposure to endocrine-disrupting chemicals (EDCs) is an emerging risk factor for development of complications later in life and in subsequent generations. We previously demonstrated that exposure to the EDC organotin (OT), which is present in contaminated seafood, resulted in reproductive abnormalities in female rats. However, few studies have explored the effect of OT accumulation in seafood on pregnancy outcomes. This led us to consider the potential effects of the OT present in seafood on fertility, pregnancy, the placenta, and the offspring. In this investigation, we assessed whether exposure to the OT in contaminated seafood resulted in abnormal fertility and pregnancy features and offspring complications. OT in contaminated seafood (LNI) was administered to female rats, and their fertility, pregnancy outcomes, and fetal liver morphology were assessed. LNI caused abnormal fertility, a reduction in the total number of pups, and an increase in serum testosterone levels compared to controls. Furthermore, LNI exposure caused irregular uterine morphology with inflammation and fibrosis and led to a reduction in embryonic implantation. In pregnant rats, LNI caused abnormal lipid profiles and livers with steatosis features. LNI exposure also causes placental morpho-physiology disruption, a high presence of glycogen and inflammatory cells, and irregular lipid profiles. In addition, LNI exposure caused an increase in large amounts of carbohydrate and lipid delivery to the fetus via an increase in placental nutrient sensor protein expressions (GLUT1, IRβ/mTOR and Akt). In both genders of offspring, LNI exposure led to an increase in body weights, liver megakaryocytes, lipid accumulation, and oxidative stress (OS) levels. Collectively, these data suggest that OT exposure from contaminated seafood in female rats leads to reduced fertility, uterine implantation failure, pregnancy and placental metabolic outcome irregularities, offspring adiposity, liver steatosis, and an increase in OS. Furthermore, some of the effects of OT may be the result of obesogenic and multigenerational effects of OT in adult female rats.

The incudopetrosal joint of the human middle ear: a transient morphology in fetuses.

In spite of the amount of research on fetal development of the human middle ear and ear ossicles, there has been no report showing a joint between the short limb of incus and the otic capsule or petrous part of the temporal bone. According to observations of serial histological sections from 65 embryos and fetuses at 7-17weeks of development, the incudopetrosal joint exhibited a developmental sequence similar to the other joints of ossicles, with an appearance of an interzone followed by a trilaminar configuration at 7-12weeks, a joint cavitation at 13-15weeks and development of intraarticular and capsular ligaments at 16-17weeks. These processes occurred at the same time or slightly later than any other joint. Thus, the joint development might coordinate with vibrating ossicles in utero. The growing short limb of incus appeared to accelerate an expansion of the epitympanic recess of the tympanic cavity. Additional observations of five late-stage fetuses demonstrated the incudopetrosal joint located in the fossa incudis joint changing to syndesmosis. Consequently, a real joint with a cavity existed transiently between the human neurocranium and the first pharyngeal arch derivative (i.e. incus) in contrast to the tympanostapedial joint or syndesmosis between the neurocranium and the second arch derivative. The newly described joint might have an effect on the widely accepted primary jaw concept: the mammalian jaw should thus have been created within the first pharyngeal arch, although the connection with neurocranium by the stapes is of a different origin.