Later Stages Of Gestation Research Articles

Crying in the Womb: Emotions, Sound, and Personhood in Early Modern England

ABSTRACT Crying in the womb (vagitus uterinus) was an extraordinary phenomenon or prodigy by which a foetus in the later stages of gestation could be heard to cry before its birth. This article traces the way that crying in the womb in early modern England was consistently interpreted, across religious, medical, and popular texts, as an emotional expression. Hearing crying in the womb affirmed the unseen presence of a body and soul, already miserable with sin and able to convey this humanness, and affect the emotions of others, with the sound of its voice. This article reveals that hearing non-verbal emotional expressions was central to the early configuration of English Protestant personhood.

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.

Development of a humanized mouse model with functional human materno-fetal interface immunity.

Materno-fetal immunity possesses specialized characteristics to ensure pathogen clearance while maintaining tolerance to the semiallogeneic fetus. Most of our understanding on human materno-fetal immunity is based on conventional rodent models that may not precisely represent human immunological processes owing to the huge evolutionary divergence. Herein, we developed a pregnant human immune system (HIS) mouse model through busulfan preconditioning, which hosts multilineage human immune subset reconstitution at the materno-fetal interface. Human materno-fetal immunity exhibits a tolerogenic feature at the midgestation stage (embryonic day [E] 14.5), and human immune regulatory subsets were detected in the decidua. However, the immune system switches to an inflammatory profile at the late gestation stage (E19). A cell-cell interaction network contributing to the alternations in the human materno-fetal immune atmosphere was revealed based on single-cell RNA-Seq analysis, wherein human macrophages played crucial roles by secreting several immune regulatory mediators. Furthermore, depletion of Treg cells at E2.5 and E5.5 resulted in severe inflammation and fetus rejection. Collectively, these results demonstrate that the pregnant HIS mouse model permits the development of functional human materno-fetal immunity and offers a tool for human materno-fetal immunity investigation to facilitate drug discovery for reproductive disorders.

Extraembryonic Membranes and Placentation in the Mexican Snake Conopsis lineata.

Extraembryonic membranes provide protection, oxygen, water, and nutrients to developing embryos, and their study generates information on the origin of the terrestrial egg and the evolution of viviparity. In this research, the morphology of the extraembryonic membranes and the types of placentation in the viviparous snake Conopsis lineata are described through optical microscopy during early and late gestation. When embryos develop inside the uterus, they become surrounded by a thin eggshell membrane. In early gestation, during stages 16 and 18, the embryo is already surrounded by the amnion and the chorion, and in a small region by the chorioallantois, which is product of the contact between the chorion and the growing allantois. A trilaminar omphalopleure covers the yolk sac from the embryonic hemisphere to the level of the equator where the sinus terminalis is located, and from there a bilaminar omphalopleure extends into the abembryonic hemisphere. Thus, according to the relationship of these membranes with the uterine wall, the chorioplacenta, the choriovitelline placenta, and the chorioallantoic placenta are structured at the embryonic pole, while the omphaloplacenta is formed at the abembryonic pole. During late gestation (stages 35, 36, and 37), the uterus and allantois are highly vascularized. The allantois occupies most of the extraembryonic coelom and at the abembryonic pole, it contacts the omphaloplacenta and form the omphalallantoic placenta. This is the first description of all known placenta types in Squamata for a snake species member of the subfamily Colubrinae; where an eggshell membrane with 2.9 μm in width present throughout development is also evident. The structure of extraembryonic membranes in C. lineata is similar to that of other oviparous and viviparous squamate species. The above indicates not only homology, but also that the functional characteristics have been maintained throughout the evolution of the reproductive type.

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.

Emotional temperaments in advanced pregnant goats and its relationship with the feto-maternal blood flow and placentome echotexture

The current study aimed to investigate the effect of xylazine sedation (non-sedated versus sedated conditions) and animal temperament on the fetal and maternal hemodynamics during the late stage of gestation in goats. In addition, it aimed to study the concentrations of cortisol and the echotexture of the placentome. Fourteen goats were assigned into two equal groups (n = 7, each) based on the animal’s emotional temperament (calm versus nervous groups). All goats were examined for assessment of the blood flow within the fetal aorta (FA), umbilical artery (UMA), and middle uterine artery (MUA) using color-pulsed Doppler ultrasonography. Goats were exposed to light sedation using the recommended dose of xylazine (0.05 mg/Kg Bw) intramuscularly. Goats in each group were reassessed for the studied parameters after sedation. Blood samples were drawn to determine the concentrations of cortisol. Placentome echotexture pixel intensity (PXI) was evaluated using computer image analysis software. Results revealed the significant impact of the xylazine sedation on the Doppler indices of the blood flow within the measured arteries (FA, UMA, and MUA), the PXI of placentome echotexture, and cortisol concentrations. The emotional temperament of goats had significant effects on the blood flow parameters of the MUA and UMA, concentrations of cortisol, and the PXI of the placentome. The interaction effect (sedation x temperament) was noticed in the measured parameters of the UMA blood flow, fetal heart rate, and cortisol concentrations. In conclusion, xylazine sedation and emotional temperaments induced alterations in the echotexture of the placentomes as well as the hemodynamic parameters of late-stage pregnant goats without affecting the pregnancy outcomes.

Longitudinal skeletal growth and growth plate morphological characteristics of chondro-tissue specific CUL7 knockout mice

Background3 M syndrome is first reported in 1975，which characterized by severe pre- and postnatal growth retardation, skeletal malformation and facial dysmorphism. These three genes (CUL7, OBSL1 and CCDC8) have been identified to be respond for 3 M syndrome, of which CUL7 is accounting for approximately 70%. To date, the molecular mechanism underlying the pathogenesis of 3 M syndrome remains poorly understood. Previous studies showed that no Cul7-/- mice could survive after birth, because of growth retardation at late gestational stage and respiratory distress after birth. The establishment of the animal model of cartilage specific Cul7 knockout mice (Cul7fl/fl;Col2a1-CreERT2 mice) has confirmed that Cul7fl/fl;Col2a1-CreERT2 mice can be selective in a time- and tissue-dependent manner, which can provide an experimental basis for further research on severe genetic diseases related to growth plates. ObjectiveTo establish a model of Cul7fl/fl;Col2a1-CreERT2 mice based on Cre/LoxP system, and to further observe its phenotype and morphological changes in growth plate. MethodsThe Cul7fl/fl;Col2a1-CreERT2 mice were taken as the experimental group, while the genotype of Cul7fl/+;Col2a1-CreERT2 mice were used as the control group. The gross morphological features and X-ray films of limbs in the two groups were observed every week for 3–6 consecutive weeks, and the length of the mice from nose to the tail, the length of femur and tibia were recorded. In the meantime, The histological morphology of tibial growth plates was compared between the two groups. ResultsA preliminary model of Cul7fl/fl;Col2a1-CreERT2 mice was established. The Cul7fl/fl;Col2a1-CreERT2 mice had abnormally short and deformed limbs (P<0.05), increased thickness of growth plate, the disorderly arranged chondrocyte columns, decreased number of cells in the proliferation zone, changes in the shape from flat to round, obviously expanded extracellular matrix, and disordered arrangement, thickening and loosening of bone trabecula at the proximal metaphysis of the femur. ConclusionsThe knockout of Cul7 gene may affect both the proliferation of chondrocytes and the endochondral osteogenesis, confirming that Cul7 is essential for the normal development of bone in the body.

Guyton perspective in managing peripartum cardiomyopathy patient with pulmonary edema: a case report

BackgroundPeripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related condition characterized by left ventricular dysfunction and heart failure, typically occurring in the peripartum period. Individuals with a history of preeclampsia and hypertension are particularly prone to developing PPCM. Recent research suggests that the condition may be triggered by vascular dysfunction influenced by maternal hormones in the late stages of gestation. The onset of left heart failure results in decreased cardiac output, leading to insufficient perfusion, which in turn, contributes to pulmonary edema and exacerbates tissue hypoxia. This cardiovascular response activates the neurohumoral system, causing peripheral vasoconstriction and elevating both mean capillary filling pressure (MCFP) and central venous pressure (CVP). Early administration of furosemide reduces volume overload due to negative cumulative fluid balance gaining and vasodilation, which increases the velocity of intravascular refilling and causes interstitial edema to resolve. This will decrease interstitial fluid pressure, resulting in decreased mechanical compression to systemic capillary and systemic vein pressure, thus decreasing MCFP and CVP subsequently. Reduced CVP also contributes to increased venous return by decreasing the gradient pressure between MCFP and CVP, resulting in increased cardiac output (CO) and improved tissue oxygenation.CaseA 33-year-old Asian woman, para 3 at full term pregnancy, admitted to the intensive care unit (ICU) after c-section and tubectomy due to shortness of breath and palpitation. Based on history taking, physical examination and echocardiography the patient fulfilled the criteria of PPCM which was also complicated by pulmonary edema. Despite impending respiratory failure, the patient rejected intubation and continuous positive airway pressure (CPAP), and was given oxygen supplementation through nasal cannula. Furosemide was given rapidly continued by maintenance dose and CVP was monitored. Antihypertensive drug, anticoagulants, and bromocriptine were also administered. After achieving negative cumulative fluid balance the patient’s symptoms resolved and was discharged one week later.ConclusionThere is a correlation between negative cumulative fluid balance and reduced central venous pressure after early furosemide therapy. Suspicion for PPCM should not be lowered in the presence of preeclampsia, it could delay appropriate treatment and increase the mortality.

Fish Oil Supplementation as an Omega-3 Fatty Acid Source during Gestation: Effects on the Performance of Awassi Ewes and Their Offspring.

The primary aim of this research was to assess the impact of supplementing fish oil into the diet of pregnant Awassi ewes on various aspects of the dam's productive performance, offspring birth weight, colostrum yield and quality, milk production and composition, postpartum offspring performance, and the composition of fatty acids in milk. In this study, two different fat sources, namely palm oil (PO) and fish oil (FO), were utilized, with both being included at a rate of 2.4% of dietary dry matter (DM) during the initial 65 days of gestation (early gestation stage), and then at 2.1% DM from day 65 of gestation until lambing (late gestation stage). The study subjects were Awassi ewes with a body weight (BW) averaging 57 ± 1.5 kg and an age of 3.5 ± 1.2 years. These ewes were randomly assigned to one of four dietary treatments: (i) a diet containing only palm oil from day 0 to day 150 of pregnancy (PO, n = 15); (ii) a diet containing palm oil from day 0 to day 65 of pregnancy, followed by a diet containing fish oil from day 66 to day 150 of pregnancy (POFO, n = 16); (iii) a diet containing fish oil from day 0 to day 65 of pregnancy, followed by a diet containing palm oil from day 66 to day 150 of pregnancy (FOPO, n = 16); (iv) a diet containing only fish oil from day 0 to day 150 of pregnancy (FO, n = 16). Within each treatment, ewes were housed in three replicates, with each replicate further divided into three subgroups. The first two subgroups each contained eight ewes, while the third subgroup contained nine ewes. In addition, each treatment contained 10 primiparous and 15 multiparous ewes. The results indicated that the POFO treatment led to significant increases (p < 0.05) in birth weight, gestation length, and colostrum IgG concentration. However, it also resulted in a decrease (p < 0.001) in colostrum production and a reduction (p < 0.001) in the percentage of milk fat and milk protein. Furthermore, the milk from the POFO treatment exhibited higher levels of polyunsaturated fatty acids (PUFAs) (p < 0.001) compared to the PO and FOPO treatments, while the milk saturated fatty acids (SFA) were lower (p < 0.001). In conclusion, the addition of fish oil at a rate of 2.1% DM during the late pregnancy period showed promise for enhancing birth weight, colostrum IgG concentration, and the PUFA content in the milk.

The normality of the first-trimester placentae collected from elective terminations

Placentae collected from elective terminations during the first trimester are commonly used as control samples in research. However, it is widely acknowledged that many complications of pregnancies can occur or originate during the early stage of gestation. This raises the question that the placentae collected from the first trimester may not accurately reflect normal placental conditions. In this study, 95 placentae were collected from elective terminations and histology was performed. Out of these, 53 placentae (56 %) exhibited the typical structure of placental villi, indicating normal development. However, 42 placentae (44 %) showed placental hydrops, with varying degrees of severity (mild, moderate, or severe). Placental hydrops has been linked to several complicated pregnancies in the later stages of gestation. Our findings suggest that the development of pregnancy pathologies could start in the first trimester, as observed by the presence of hydrops. Placental researchers should be aware of when using first-trimester placentae from termination as controls in studies. However, it remains unclear whether pathological morphologies resolve or ameliorate as the pregnancy progression or whether such placentae continue to have such pathology, but clinical symptoms/signs do not manifest.

Recurrence quantification analysis of uterine vectormyometriogram to identify pregnant women with threatened preterm labor

Electrohysterography has been shown to provide relevant information on preventing preterm labor. Recent studies have confirmed the feasibility of using the vectormyometriogram (VMG) to assess uterine myoelectric vector displacement, with different physiological implications for the slow and fast waves, without suggesting its implementation in clinical practice. The fast wave VMG component has dynamic behavior in any specific direction on the X-Y plane. Since recurrence is a common feature of dynamic systems, we aimed to determine the recurrence pattern of uterine vector displacement, exploring its clinical potential in detecting imminent and preterm labor in women with threatened preterm labor and a serious preterm birth risk. For this, we analyzed the recurrence patterns from a 2D-vectormyometriogram using four common statistics: determinism, longest diagonal, entropy, and laminarity. We found significantly increased determinism (0.035 ± 0.011 vs. 0.077 ± 0.041), entropy (1.768 ± 0.116 vs. 2.197 ± 0.24) and laminarity (0.086 ± 0.034 vs. 0.173 ± 0.078) from the early (26–30 weeks) to late (35–37 weeks) gestation stages. As pregnancy progresses, the uterine vector displacement becomes more periodic, predictable and stable, while VMG recurrence statistics in the fast wave high bandwidth better detect imminent and preterm labor, outperforming classical EHG parameters from bipolar channels. The proposed method was also resistant to motion artifacts and preserved its discriminative capacity between the groups. Our results on VMG recurrence statistics could thus be another reliable biomarker for preventing preterm labor in women with threatened preterm labor and would favor transferring the EHG technique to clinical practice.

PSIII-9 Bacterial Community Diversity in Reproductive Tissues and Fetal Fluids of Pregnant Gilts

Abstract The fertility status of women has previously been linked to shifts in bacterial diversity within the reproductive tract. The objective of this study was to analyze the diversity of bacterial populations within reproductive tissues (i.e., vagina, cervix, endometrium, and chorion) and fetal fluids (i.e., allantoic and amniotic) of pregnant gilts. Crossbred gilts free of physical, health or reproductive-related issues were euthanized and hysterectomized during the preimplantation (D11, n = 7), implantation (D15, n = 5), mid-gestation (D60, n = 6), and late gestation (D90, n = 6) stages of pregnancy. Sterile swabs were rotated 8 times to collect samples from the mucosal surface of individual tissues and immediately placed in microcentrifuge tube for storage (-80°C) until sequencing. A one cm incision was made to expose the endometrium and cervix, whereas for vaginal sampling, sterile swabs were inserted 6 inches past the vulva and then rotated. For collection of samples of chorion, an incision was made in the endometrium, exposing the chorioallantois to allow sampling of the chorion adjacent to the endometrium, while the allantoic epithelial surface of the chorioallantois was sampled directly. For allantoic and amniotic fluids, 5 mL samples were collected and placed immediately in sterile 10 mL conical tubes and stored (-80°C) for sequencing targeting the V4 hypervariable region of the 16S rRNA gene. Quality of all samples was determined by FastQC before being processed for taxon analysis using the qiime2 pipeline. Alpha diversity (within sample metric) was analyzed using the Kruskal-Wallis test, whereas PERMANOVA was performed for beta diversity analysis (between sample metric). Shannon’s index, an alpha diversity metric, indicated contrasts in diversity by day (P = 0.02). A pairwise comparison indicated that D15 had greater alpha diversity (Shannon’s index) compared with D60 and D90 (4.89 ± 0.20 vs. 3.96 ± 0.19 and 4.10 ± 0.18, respectively; P &amp;lt; 0.05). Differences in alpha diversity by tissue and fluid type were detected with a pairwise comparison indicating that amniotic fluid had the lowest alpha diversity compared with the cervix (3.44 ± 0.34 vs. 4.62 ± 0.22, respectively; P = 0.04). For beta diversity, PERMANOVA and PCoA plots for unweighted UniFrac demonstrated significant clustering by day (P &amp;lt; 0.01), with clusters being D11 and D15 vs. D60 and D90. Additionally, PERMANOVA and PCoA plots for unweighted UniFrac indicated significant clustering by tissue and fluid type (P &amp;lt; 0.01), with distinct clustering from the external portion of the reproductive tract (i.e., vagina) to the internal portion (i.e., amniotic and allantoic fluids). Based on these results, bacterial diversity within the reproductive tract shifts changes depending on the stage of pregnancy. Moreover, bacterial diversity decreases as you move from the external surface of the reproductive tubes towards the fetus (i.e., least in the amniotic fluid).

87 Improving Pig Livability Before, During, and After Parturition

Abstract Nearly a quarter of piglets are lost from farrowing to weaning, with stillbirths representing about 7.5% and preweaning mortality contributing another 15.7% in North America (Pigchamp, Metafarm). This averages to a loss of 7.37 pigs per sow per year resulting in significant economic loss and animal welfare concerns. Main contributors of low piglet survivability include poor sow body condition at farrowing, long farrowing duration, piglet asphyxiation, insufficient colostrum consumption, and health challenges. Piglet livability can be improved through nutrition and management solutions before, during, and after parturition. In this context three main strategies have been shown to be effective: 1) managing sow body composition, 2) improving fetal oxygen and nutrient supply via the nitric oxide pathway, and 3) improving piglet health through functional ingredients in the diet of the sow. Highly prolific sows (&amp;gt; 16 born alive) lose both backfat and muscle during the later stages of gestation. Additionally, loin depth loss is more detrimental for piglet survival compared with backfat loss. Sows with the highest stillborn (&amp;gt; 2 per litter) lose the most loin muscle depth regardless of genetics. A solution to reduce this effect and improve piglet survivability is a two-phase gestation feeding with more amino acids in late gestation. Average farrowing duration of a highly prolific sow is 300 minutes and increasing with larger litters. To make things worse, most sows are going through farrowing without food and/or drink. Nutrients and energy supply to sow are critical for shorting farrowing duration and piglet survivability. Compared with pigs that died before weaning, surviving pigs at weaning have greater blood oxygen and less carbon dioxide and lactate at birth. Nitric oxide boosting technologies have been used widely to enhance athletic performance and increase endurance. This vasodilative effect of nitric oxide can be used similarly in sows to increased placental blood flow and thus oxygen and nutrient supply to fetuses. This reduces the risk of asphyxiation and therefore can increase piglet vitality at birth and decreases stillbirth and pre-weaning mortality. Post-parturition health challenge poses a large risk to piglet survivability. Functional feed ingredients, such as botanicals, are a potential solution to improve piglet health and resilience to challenging conditions. Some botanicals can pass through placenta and milk to supply piglets. Milk from sows fed specific botanicals has been shown to improve inhibitory activity against Bacillus subtilis and Staphylococcus aureus. Some specific botanicals can improve sow and piglet antioxidant status, and piglet gut health. In conclusion, managing sow body condition, nitric oxide pathway stimulation, and functional sow diets are effective ways to improve piglet survivability in challenging environments.

Pregnancy and neonatal outcomes of SARS-CoV-2 infection discovered at the time of delivery: a tertiary center experience in North Italy.

Although the knowledge on SARS-CoV-2 infection in pregnancy has greatly improved, there is still a lack of information on its role in the later stages of gestation. The aim of this study is to investigate whether SARS-CoV-2 discovered at delivery is associated with any obstetric or neonatal complications. A retrospective case-control study was conducted at Department of Obstetrics, University Hospital Maggiore della Carità, Novara, Italy, from March 2020 to March 2023. Pregnant women admitted were tested for SARS-CoV-2. 168 women resulted positive at the time of delivery; the women were asymptomatic or paucisymptomatic. 170 negative women were selected as controls, selecting, for each SARS-CoV-2 positive patient, the patient who gave birth right before, if negative. Demographic and anamnestic characteristics, pregnancy, labor, and neonatal outcomes were evaluated. SARS-CoV-2 positive patients were more likely to have gestational diabetes (13.7 vs. 5.3 %) and required less frequently intrapartum analgesia (11.3 vs. 27 %) and labor augmentation (7.3 vs. 16.5 %). Post-partum hemorrhage rate was lower (13.7 vs. 22.9 %) and a shorter length of first and second stage of labor occurred. There were no statistically significant differences between the two groups regarding the mode of delivery and neonatal outcomes. SARS-CoV-2 positive patients have shorter labor length and a lower incidence of postpartum hemorrhage. Fewer obstetric interventions, as well as less use of intrapartum analgesia and oxytocin, could explain these findings. Moreover, gestational diabetes could increase susceptibility to infection. SARS-CoV-2 infection discovered at the time of delivery in asymptomatic or paucisymptomatic patients does not appear to increase the rate of cesarean delivery or other obstetric complications, and neonatal outcomes have not worsened.

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence.

Identification of unique and specific biomarkers to better detect and quantify senescent cells remains challenging. By a global proteomic profiling of senescent human skin BJ fibroblasts induced by ionizing radiation (IR), the cellular level of pregnancy zone protein (PZP), a presumable pan-protease inhibitor never been linked to cellular senescence before, was found to be decreased by more than 10-fold, while the level of PZP in the conditioned medium was increased concomitantly. This observation was confirmed in a variety of senescent cells induced by IR or DNA-damaging drugs, indicating that high-level secretion of PZP is a novel senescence-associated secretory phenotype. RT-PCR examination verified that the transcription of the PZP gene is enhanced in various cells at senescence or upregulated following DNA damage treatment in a p53-independent manner. Moreover, pretreatment with late pregnancy serum containing a high level of PZP led to inhibition of doxorubicin-induced senescence in A549 cells, and depletion of PZP in the pregnancy serum could enhance such inhibition. Finally, the addition of immuno-precipitated PZP complexes into tissue culture attenuated the growth of A549 cells and promoted the spontaneous senescence. Therefore, we revealed that high-level secretion of PZP is a novel and unique feature associated with DNA damage-induced senescence, and secreted PZP is a positive regulator of cellular senescence, particularly during the late stage of gestation.

O-Linked N-Acetylglucosamine Transferase Ensures Survival of Mouse Fetal Liver Hematopoietic Progenitors Partly by Regulating Bcl-xL and Oxidative Phosphorylation.

O-linked N-acetylglucosamine transferase (OGT) critically regulates wide variety of biological processes such as gene expression, metabolism, stress response, signaling and proteostasis. In adult hematopoiesis, OGT is crucial for differentiation of B and T cells and the maintenance of hematopoietic stem cells (HSCs). However, a role for OGT in fetal liver (FL) hematopoiesis remains unknown. To investigate a role for OGT in FL hematopoiesis, we conditionally disrupted OGT in hematopoietic cells in developing FLs. Hematopoietic specific disruption of OGT resulted in embryonic lethality in late stage of gestation due to severe anemia and growth retardation. OGT loss led to profound reduction of differentiating erythroid cells and erythroid progenitors in FLs due to massive apoptosis. In addition, clonogenic capacity of FL cells was severely impaired by OGT loss. Interestingly, expression of BCL-XL, a well-known inhibitor of apoptosis in FL cells, dramatically decreased, and the levels of reactive oxygen species (ROS) were increased in OGT-deficient FL cells. Overexpression of Bcl-xL and reduction of ROS significantly restored the colony formation of OGT-deficient FL cells. This study revealed a novel role for OGT during embryogenesis, which ensures survival of FL hematopoietic cells partly by regulating Bcl-xL and oxidative phosphorylation.

Standardized ileal digestibility of amino acids in soybean meal fed to non-pregnant and pregnant sows

BackgroundTwo studies were designed to determine standard ileal crude protein (CP) and amino acid (AA) digestibility of soybean meal (SBM) from different origins fed to non-pregnant and pregnant sows. Seven solvent-extracted SBMs from soybeans produced in the USA, Brazil, and China were selected. In Exp. 1, eight different diets were created: a nitrogen (N)-free diet and 7 experimental diets containing SBM from different origins as the only N source. Eight non-pregnant, multiparous sows were arranged in an 8 × 8 Latin square design (8 periods and 8 diets). In Exp. 2, the diet formula was the same as in Exp. 1. Eight gestating sows (parity 3) were assigned to 4 different diets in a replicated 4 × 3 Youden square design (three periods and four diets) in mid-gestation and again in late-gestation stages.ResultsWhen fed to non-pregnant and late-gestating sows, the standardized ileal digestibility (SID) of CP and most AAs from different SBM were not significantly different (P > 0.05). When fed to mid-gestating sows, the SID values for Arg, His, Lys, Phe, Cys, Gly, Ser, and Tyr in SBM 1 were lower than in SBM 4 and 5 (P < 0.05), whereas SID for Leu from SBM 5 was higher than in SBM 1 and 4 (P < 0.05). SID values for Ile, Ala, and Asp from SBM 4 were lower than in SBM 1 and 5 (P < 0.05). Sows had significantly greater SID values for Lys, Ala, and Asp during mid-gestation when compared with late-gestation stages (P < 0.05). Mid-gestating sows had greater SID value for Val and lower SID value for Tyr when compared with non-pregnant and late-gestating sows (P < 0.01), whereas non-pregnant sows had significantly greater SID value for Met when compared with gestating sows (P < 0.01).ConclusionsWhen fed to mid-gestating sows, the SID values for most AAs varied among SBM samples. The SID values for Lys, Met, Val, Ala, Asp, and Tyr in SBM were affected by sow gestation stages. Our findings provide a cornerstone for accurate SBM use in sow diets.

Assembloid CRISPR screens reveal impact of disease genes in human neurodevelopment.

The assembly of cortical circuits involves the generation and migration of interneurons from the ventral to the dorsal forebrain1-3, which has been challenging to study at inaccessible stages of late gestation and early postnatal human development4. Autism spectrum disorder and other neurodevelopmental disorders (NDDs) have been associated with abnormal cortical interneuron development5, but which of these NDD genes affect interneuron generation and migration, and how they mediate these effects remains unknown. We previously developed a platform to study interneuron development and migration in subpallial organoids and forebrain assembloids6. Here we integrate assembloids with CRISPR screening to investigate the involvement of 425 NDD genes in human interneuron development. The first screen aimed at interneuron generation revealed 13 candidate genes, including CSDE1 and SMAD4. We subsequently conducted an interneuron migration screen in more than 1,000 forebrain assembloids that identified 33 candidate genes, including cytoskeleton-related genes and the endoplasmic reticulum-related gene LNPK. We discovered that, during interneuron migration, the endoplasmic reticulum is displaced along the leading neuronal branch before nuclear translocation. LNPK deletion interfered with this endoplasmic reticulum displacement and resulted in abnormal migration. These results highlight the power of this CRISPR-assembloid platform to systematically map NDD genes onto human development and reveal disease mechanisms.

Exposure to di-isononyl phthalate during early pregnancy disrupts decidual angiogenesis and placental development in mice

Di-isononyl phthalate (DiNP), an endocrine-disrupting chemical, is found in numerous consumer products and human exposure to this phthalate is becoming inevitable. The impact of DiNP exposure on the establishment and maintenance of pregnancy remains largely unknown. Thus, we conducted studies in which pregnant mice were exposed to an environmentally relevant dose (20 µg/kg BW/day) of DiNP on days 1–7 of gestation, then analyzed the effects of this exposure on pregnancy outcome. Our studies revealed that exposure to DiNP during this window led to fetal loss towards the end of gestation. Further studies showed that, although embryos were able to attach to the uterus, implantation sites in DiNP-exposed uteri exhibited impaired differentiation of stromal cells to decidual cells and an underdeveloped angiogenic network in the decidual bed. We also found that exposure to this phthalate has a significant effect on trophoblast differentiation and causes disorganization of the placental layers. The labyrinth was significantly reduced, resulting in compromised expression of nutrient transporters in the placentas of mice exposed to DiNP. These placental defects in DiNP-exposed females were the cause of fetal loss during the later stages of gestation.

Dietary Supplementation with Different Types of Potassium and Magnesium during Late Gestation and Lactation Modulates the Reproductive Performance, Antioxidant Capacity, and Immune Function of Sows

The objective of this study was to investigate the effects of dietary supplementation with different types of potassium and magnesium on the reproductive performance, antioxidant capacity, and immunity of sows. Forty-five Landrace × Yorkshire sows at the late gestation stage (85 d) were randomly assigned to three groups (n = 15). Sows in the control group (CON), potassium chloride and magnesium sulfate group (PM), and potassium-magnesium sulfate group (PMS) were fed with a basal diet, a basal diet supplemented with magnesium sulfate (0.20%) and potassium chloride (0.15%), or a basal diet supplemented with potassium-magnesium sulfate (0.45%), respectively. The results showed that dietary supplementation with PMS did not yield significant effects on the reproductive performance compared with the CON group (p &gt; 0.05). However, it significantly elevated the level of insulin-like growth factor 1 (IGF-1) in plasma and immunoglobulin A (IgA) in colostrum (p &lt; 0.05). Furthermore, PMS significantly augmented the activities of catalase (CAT) and superoxide dismutase (SOD) while reducing the levels of malondialdehyde (MDA) in comparison to the CON group (p &lt; 0.05). Compared with the PM group, the PMS group significantly reduced the incidence rate of intrauterine growth restriction (IUGR) (p &lt; 0.05) and significantly decreased the concentration of the proinflammatory cytokine (TNF-α) level in plasma (p &lt; 0.05). These results indicated that dietary supplementation with PMS during late gestation could enhance sows’ antioxidant capacity and the IgA level in colostrum. These findings will provide a theoretical reference for the use of magnesium and potassium in sow production to improve sows’ health.