Maternal Hypermethylated Genes Contribute to Intrauterine Growth Retardation of Piglets in Rongchang Pigs.

The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) (p < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.

Dietary supplementation with dihydroartemisinin improves intestinal barrier function in weaned piglets with intrauterine growth retardation by modulating the gut microbiota.

The aim of this study was to investigate whether dietary dihydroartemisinin (DHA) supplementation could improve intestinal barrier function and microbiota composition in intrauterine growth restriction (IUGR) weaned piglets. Twelve normal birth weight (NBW) piglets and 24 IUGR piglets at 21 d of age were divided into three groups, which were fed a basal diet (NBW-CON and IUCR-CON groups) and an 80 mg/kg DHA diet (IUGR-DHA group). At 49 d of age, eight piglets of each group with similar body weights within groups were slaughtered, and serum and small intestine samples were collected. The results showed that IUGR piglets reduced growth performance, impaired the markers of intestinal permeability, induced intestinal inflammation, decreased intestinal immunity, and disturbed the intestinal microflora. Dietary DHA supplementation increased average daily gain, average daily feed intake, and body weight at 49 d of age in IUGR-weaned piglets (P < 0.05). DHA treatment decreased serum diamine oxidase activity and increased the numbers of intestinal goblet cells and intraepithelial lymphocytes, concentrations of jejunal mucin-2 and ileal trefoil factor 3, and intestinal secretory immunoglobin A and immunoglobin G (IgG) concentrations of IUGR piglets (P < 0.05). Diet supplemented with DHA also upregulated mRNA abundances of jejunal IgG, the cluster of differentiation 8 (CD8), major histocompatibility complex-I (MHC-I), and interleukin 6 (IL-6) and ileal IgG, Fc receptor for IgG (FcRn), cluster of differentiation 8 (CD4), CD8, MHC-I, IL-6 and tumor necrosis factor α (TNF-α), and enhanced mRNA abundance and protein expression of intestinal occludin and ileal claudin-1 in IUGR piglets (P < 0.05). In addition, DHA supplementation in the diet improved the microbial diversity of the small intestine of IUGR piglets and significantly increased the relative abundance of Actinobacteriota, Streptococcus, Blautia and Streptococcus in the jejunum, and Clostridium sensu_ stricto_in the ileum (P < 0.05). The intestinal microbiota was correlated with the mRNA abundance of tight junction proteins and inflammatory response-related genes. These data suggested that DHA could improve the markers of intestinal barrier function in IUGR-weaned piglets by modulating gut microbiota. DHA may be a novel nutritional candidate for preventing intestinal dysfunction in IUGR pigs.

Intrauterine growth retardation (IUGR) is defined as the restricted development of the mammalian fetus or its organs during pregnancy, which has high morbidity and mortality during the perinatal period and improves the risk of metabolic diseases in the long term. Dihydroartemisinin (DHA) is a derivative of artemisinin that possesses anti-inflammatory and immunoregulatory effects. Therefore, this experiment was conducted to investigate whether dietary DHA supplementation could improve the intestinal barrier function and microbiota composition in IUGR-weaned piglets. The result showed that IUGR could lead to intestinal barrier dysfunction. Dietary supplementation with DHA improved growth performance and attenuated intestinal barrier dysfunction by decreasing the markers of intestinal permeability, increasing the mucus layer barrier, enhancing immunity, and reducing the inflammatory response in IUGR piglets, which may be attributed to the improvement of the intestinal microbiota. Moreover, the study indicated that the gut microflora was correlated with the gene expression of tight junction proteins and immune function. This study may provide a new nutritional strategy for the maintenance of intestinal health in IUGR pigs.

Puerarin Affects 1HMR Spectroscopy Quantified Hepatic Fat Signal Fraction in Intrauterine Growth Restricted Rats.

OBJECTIVE: This study aimed to investigate the impact of puerarin early intervention on growth parameters and Hepatic Fat Signal Fraction (HFF) quantification in Intrauterine Growth Restricted(IUGR)rats through Proton Magnetic resonance spectroscopy (1H-MRS). METHODS: Pregnant rats were divided into three groups: control, IUGR with puerarin treatment, and IUGR without treatment. The treatment and nontreatment groups were received a low-protein diet during pregnancy, while the control group received a normal diet. After birth, pups in the treatment group received a unilateral intraperitoneal injection of 50 mg/kg/d puerarin. Male rats were evaluated at 3,8 and 12 weeks, including measurements of weight, body length and waist circumference and body mass index (BMI). Conventional magnetic resonance imaging and 1HMRS were conducted using a 3.0 T whole-body MR scanner. RESULTS: Newborn pups in the treatment and non-treatment groups showed significantly lower body weight, BMI, and body length at 3 weeks compared to the control group. However, there were no significant differences in HFF and waist circumference between the three groups at 3 weeks. At 8 and 12 weeks post-delivery, significant differences in body weight, BMI, waist circumference were observed in newborn pups of IUGR non-treatment rats compared to the control group. In contrast, there were no significant differences in body weight, BMI, waist circumference between the treatment group and the control group at 8 and 12 weeks. Moreover, the treatment group exhibited notably higher HFF compared to the control group at both time points. At 12 weeks post-birth, a significant difference in HFF was observed between the IUGR non-treatment and treatment groups, although no significant difference was found at 8 weeks. CONCLUSION: Early intervention with puerarin following birth has a significant impact on liver fat content and may potentially reduce adult obesity among IUGR rats.

The interaction of ER stress and autophagy in trophoblasts: navigating pregnancy outcome.

The endoplasmic reticulum (ER) is a complex and dynamic organelle that initiates unfolded protein response (UPR) and endoplasmic reticulum stress (ER Stress) in response to the accumulation of unfolded or misfolded proteins within its lumen. Autophagy is a paramount intracellular degradation system that facilitates the transportation of proteins, cytoplasmic components, and organelles to lysosomes for degradation and recycling. Preeclampsia (PE) and intrauterine growth retardation (IUGR) are two common complications of pregnancy associated with abnormal trophoblast differentiation and placental dysfunctions and have a major impact on fetal development and maternal health. The intricate interplay between ER Stress, and autophagy and their impact on pregnancy outcomes, through mediating trophoblast differentiation and placental development, has been highlighted in various reports. Autophagy controls trophoblast regulation through a variety of gene expressions and signalling pathways while excessive ER Stress triggers downstream apoptotic signalling, culminating in trophoblast apoptosis. This comprehensive review delves into the intricacies of placental development and explores the underlying mechanisms of PE and IUGR. In addition, this review will elucidate the molecular mechanisms of ER Stress and autophagy, both individually and in their interplay, in mediating placental development and trophoblast differentiation, particularly highlighting their roles in PE and IUGR development. This research seeks to the interplay between ER Stress and impaired autophagy in the placental trophoderm, offering novel insights into their contribution to pregnancy complications.

Adams-Oliver syndrome: About a case.

We report the case of a newborn with aplasia cutis congenita characterized by the absence of skin in the left parietal region, superficial dilatation of the scalp veins, facial dysmorphia, limb anomalies, and severe intrauterine growth retardation. Maternal milk enabled the baby to gain weight, and dermatological treatment was performed for scarring of the vertex. Psychomotor development and stature were spectacular. This case illustrates the clinical variability of this condition and the need for multidisciplinary management.

Postnatal growth failure of very low-birth-weight infants in Southwest Iran: A descriptive analytical study.

Background and Aims: Preterm infants are more prone to poor growth and neurodevelopment. The first few weeks of life play an important role in the growth and neurodevelopment of very-low-birth-weight (VLBW) infants. The Vermont Oxford Network, evaluating the postnatal growth of preterm newborns, considers growth failure as body weight <10th percentile for postmenstrual age. This study aims to assess the frequency of postnatal growth failure in VLBW infants in Southwest Iran. Methods: This descriptive analytical study was performed on VLBW infants in the neonatal intensive care unit (NICU) of Imam Khomeini Hospital (Ahvaz, Iran) from September 2019 to August 2020. Growth failure was confirmed when a newborn's weight at discharge was smaller than the 10th percentile corrected age (≤-1.28 Z-score), based on the Fenton growth chart as a standard. This study was performed on 353 infants. Intrauterine growth retardation was detected in 29% of female and 10.6% of male newborns, who were born at a gestational age of 32 and 31 weeks or higher respectively. Upon hospital discharge, postnatal growth failure was detected in all newborn girls, except for those born at 32 weeks of gestation, and all newborn boys, except for those born at a gestational age of 33-34 weeks. Conclusion: Postnatal growth retardation in VLBW infants born in our NICU was much higher than that of other centers. Overcrowding, short length of hospitalization, low nurse-to-patient ratio, and untrained nurses were among the reasons for poor postnatal growth in our center.

Cell­free fetal DNA at 11­13 weeks of gestation is not altered in complicated pregnancies.

Non-invasive maternal cell-free fetal DNA (cffDNA) is a promising biomarker for screening common genetic syndromes. Alterations in the expression levels of cffDNA in the maternal circulation have been demonstrated in abnormal pregnancies. However, the results are conflicting. The present study aimed to investigate whether cffDNA levels are associated with pregnancy complications. The study group comprised pregnant women who presented with pregnancy complications, such as preterm birth, gestational hypertension, intrauterine growth retardation, gestational diabetes, polyhydramnios, oligohydramnios, vaginal bleeding and placental abruption. The control group comprised women who had a normal pregnancy course. Blood samples were obtained from 500 pregnant women between 11-13 weeks of gestation. cffDNA was amplified, sequenced and analyzed using the next-generation aneuploidy test of a Panorama-Natera kit. Nuchal translucency (NT) thickness as well as pregnancy associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were also assessed. Statistical analysis was performed in 494 out of the 500 samples collected with SPSS v.26 using non-parametric methods. The parameters were normalized by the multiples of median (MoM) method. The expression levels of PAPP-A, ß-hCG, and the NT mean MoM values were significantly different between the study and control groups (P=0.005, P<0.001 and P=0.007, respectively). However, the expression levels of cffDNA and the mean MoM values were not significantly different between these two groups (P=0.687). The findings of the present study support the conclusion that cffDNA expression is not altered in a series of pregnancy complications. The prognostic value of cffDNA in predicting adverse pregnancy outcomes requires further investigation.

Multi-organ developmental toxicity and its characteristics in fetal mice induced by dexamethasone at different doses, stages, and courses during pregnancy.

Dexamethasone is widely used in pregnant women at risk of preterm birth to reduce the occurrence of neonatal respiratory distress syndrome and subsequently reduce neonatal mortality. Studies have suggested that dexamethasone has developmental toxicity, but there is a notable absence of systematic investigations about its characteristics. In this study, we examined the effects of prenatal dexamethasone exposure (PDE) on mother/fetal mice at different doses (0.2, 0.4, or 0.8 mg/kg b.i.d), stages (gestational day 14-15 or 16-17) and courses (single- or double-course) based on the clinical practice. Results showed that PDE increased intrauterine growth retardation rate, and disordered the serum glucose, lipid and cholesterol metabolic phenotypes, and sex hormone level of mother/fetal mice. PDE was further discovered to interfere with the development of fetal lung, hippocampus and bone, inhibits steroid synthesis in adrenal and testis, and promotes steroid synthesis in the ovary and lipid synthesis in the liver, with significant effects observed at high dose, early stage and double course. The order of severity might be: ovary > lung > hippocampus/bone > others. Correlation analysis revealed that the decreased serum corticosterone and insulin-like growth factor 1 (IGF1) levels were closely related to PDE-induced low birth weight and abnormal multi-organ development in offspring. In conclusion, this study systematically confirmed PDE-induced multi-organ developmental toxicity, elucidated its characteristics, and proposed the potential "glucocorticoid (GC)-IGF1" axis programming mechanism. This research provided an experimental foundation for a comprehensive understanding of the effect and characteristics of dexamethasone on fetal multi-organ development, thereby guiding the application of "precision medicine" during pregnancy.

Novel OBSL1 Variant in a Chinese Patient with 3M Syndrome and the c.458dupG Mutation May Be a Potential Hotspot Mutation in the Chinese Population.

3M syndrome is an autosomal recessive disorder characterized by short stature and skeletal developmental abnormalities. In this study, a Chinese patient with 3M syndrome was presented. A novel OBSL1 (obscurin-like 1 gene) variant was found. The patient is a 2-year-old girl who presented with short stature and had intrauterine growth retardation and low birth weight. Gene analysis revealed compound heterozygote mutations in the OBSL1 gene: c.458dupG (p.L154Pfs*100) and c.427dupG (p.A143Gfs*111). The c.427dupG mutation is novel. The c.458dupG mutation has been documented in 5 cases, occurring only in Chinese individuals, indicating ethnic specificity. In cases of short-statured children presenting intrauterine growth retardation, low birth weight, and skeletal developmental abnormalities, 3M syndrome should be considered. The c.458dupG mutation might be a hotspot mutation in the Chinese population.

Assessment of vitamin status; A, E and D in Egyptian neonates with IUGR: a cross sectional study.

BACKGROUND: Neonates with intrauterine growth retardation (IUGR) may present with fatal complications and permanent serious consequences. Vitamin status may influence fetal development. In this study we assessed vitamin A, E and D concentrations in umbilical cord blood in newborns with IUGR. METHODS: Maternal data were obtained. Neonatal assessment included; age of gestation calculated from last menstrual period, Ultrasound (U/S), new Ballard, Apgar scores and anthropometric measurements including; Head circumference, length and weight. WHO growth percentile curves were used. Vitamin A, E and D in cord blood samples were measured by high performance liquid chromatography (HPLC) and ELISA consecutively. RESULTS: A total of 86 full term newborns were enrolled in this study, 42 (48.8%) with IUGR with gestational age (33.59 ± 1.20) week by U/S and 44 (51.2%) appropriate for gestational age neonates with gestational age (38.70 ± 1.50). Ballard and Apgar scores (p < 0.05) and Z scores for weight, length and head circumference (p < 0.001) at birth were significantly lower in neonates with Intrauterine growth retardation (IUGR) than appropriate for gestational age (AGA) neonates. The levels of Vitamin A, E and D were significantly lower in the IUGR group than the AGA (p < 0.05) for all. Significant positive correlations of weight with vitamin A, and E cord blood levels were found (p < 0.05), while length was significantly positively correlated only with vitamin A (p < 0.05). Head circumference showed significant positive correlations with the three vitamins (p < 0.05) for all. CONCLUSION: Neonates with IUGR had significantly lower levels of Vitamin A, E and D than AGA neonates. Significant positive correlations of weight with vitamin A, and E cord blood levels was detected, while neonatal length was associated only with vitamin A level. The present study highlights the significance of nutritional policies for inhibiting deficiency of these vitamins during pregnancy and childhood.

Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth.

OBJECTIVES: Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). METHODS: We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. RESULTS: No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. CONCLUSIONS: The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.

Diagnostic performance of 32 vs 36 weeks ultrasound in predicting late-onset fetal growth restriction and small-for-gestational-age neonates: a systematic review and meta-analysis.

OBJECTIVE: Fetal growth restriction is an independent risk factor for fetal death and adverse neonatal outcomes. The main aim of this study was to investigate the diagnostic performance of 32 vs 36 weeks ultrasound of fetal biometry in detecting late-onset fetal growth restriction and predicting small-for-gestational-age neonates. DATA SOURCES: A systematic search was performed to identify relevant studies published until June 2022, using the databases PubMed, Web of Science, and Scopus. STUDY ELIGIBILITY CRITERIA: Cohort studies in low-risk or unselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation were used. METHODS: The estimated fetal weight and abdominal circumference were assessed as index tests for the prediction of small for gestational age (birthweight of <10th percentile) and detecting fetal growth restriction (estimated fetal weight of <10th percentile and/or abdominal circumference of <10th percentile). The quality of the included studies was independently assessed by 2 reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. For the meta-analysis, hierarchical summary area under the receiver operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models. RESULTS: The analysis included 25 studies encompassing 73,981 low-risk pregnancies undergoing third-trimester ultrasound assessment for growth, of which 5380 neonates (7.3%) were small for gestational age at birth. The pooled sensitivities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in predicting small for gestational age were 36% (95% confidence interval, 27%-46%) and 37% (95% confidence interval, 19%-60%), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%-56%) and 50% (95% confidence interval, 25%-74%), respectively, at 36 weeks ultrasound. The pooled specificities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in detecting small for gestational age were 93% (95% confidence interval, 91%-95%) and 95% (95% confidence interval, 85%-98%), respectively, at 32 weeks ultrasound and 93% (95% confidence interval, 91%-95%) and 97% (95% confidence interval, 85%-98%), respectively, at 36 weeks ultrasound. The observed diagnostic odds ratios for an estimated fetal weight of <10th percentile and an abdominal circumference of <10th percentile in detecting small for gestational age were 8.8 (95% confidence interval, 5.4-14.4) and 11.6 (95% confidence interval, 6.2-21.6), respectively, at 32 weeks ultrasound and 13.3 (95% confidence interval, 10.4-16.9) and 36.0 (95% confidence interval, 4.9-260.0), respectively, at 36 weeks ultrasound. The pooled sensitivity, specificity, and diagnostic odds ratio in predicting fetal growth restriction were 71% (95% confidence interval, 52%-85%), 90% (95% confidence interval, 79%-95%), and 25.8 (95% confidence interval, 14.5-45.8), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%-55%), 94% (95% confidence interval, 93%-96%), and 16.9 (95% confidence interval, 10.8-26.6), respectively, at 36 weeks ultrasound. Abdominal circumference of <10th percentile seemed to have comparable sensitivity to estimated fetal weight of <10th percentile in predicting small-for-gestational-age neonates. CONCLUSION: An ultrasound assessment of the fetal biometry at 36 weeks of gestation seemed to have better predictive accuracy for small-for-gestational-age neonates than an ultrasound assessment at 32 weeks of gestation. However, an opposite trend was noted when the outcome was fetal growth restriction. Fetal abdominal circumference had a similar predictive accuracy to that of estimated fetal weight in detecting small-for-gestational-age neonates.

FUNDC1-mediated mitophagy triggered by mitochondrial ROS is partially involved in 1-nitropyrene-evoked placental progesterone synthesis inhibition and intrauterine growth retardation in mice.

Intrauterine growth retardation (IUGR) is a major cause of perinatal morbidity and mortality. Previous studies showed that 1-nitropyrene (1-NP), an atmospheric pollutant, induces placental dysfunction and IUGR, but the exact mechanisms remain uncertain. In this research, we aimed to explore the role of mitophagy on 1-NP-evoked placental progesterone (P4) synthesis inhibition and IUGR in a mouse model. As expected, P4 levels were decreased in 1-NP-exposed mouse placentas and maternal sera. Progesterone synthases, CYP11A1 and 3ßHSD1, were correspondingly declined in 1-NP-exposed mouse placentas and JEG-3 cells. Mitophagy, as determined by LC3B-II elevation and TOM20 reduction, was evoked in 1-NP-exposed JEG-3 cells. Mdivi-1, a specific mitophagy inhibitor, relieved 1-NP-evoked downregulation of progesterone synthases in JEG-3 cells. Additional experiments showed that ULK1/FUNDC1 signaling was activated in 1-NP-exposed JEG-3 cells. ULK1 inhibitor or FUNDC1-targeted siRNA blocked 1-NP-induced mitophagy and progesterone synthase downregulation in JEG-3 cells. Further analysis found that mitochondrial reactive oxygen species (ROS) were increased and GCN2 was activated in 1-NP-exposed JEG-3 cells. GCN2iB, a selective GCN2 inhibitor, and MitoQ, a mitochondria-targeted antioxidant, attenuated GCN2 activation, FUNDC1-mediated mitophagy, and downregulation of progesterone synthases in JEG-3 cells. In vivo, gestational MitoQ supplement alleviated 1-NP-evoked reduction of placental P4 synthesis and IUGR. These results suggest that FUNDC1-mediated mitophagy triggered by mitochondrial ROS may contribute partially to 1-NP-induced placental P4 synthesis inhibition and IUGR.

Effects of dietary epidermal growth factor supplementation on liver antioxidant capacity of piglets with intrauterine growth retardation.

The present experiment was conducted to study the effects of dietary epidermal growth factor (EGF) supplementation on the liver antioxidant capacity of piglets with intrauterine growth retardation (IUGR). The present study consists of two experiments. In experiment 1, six normal-birth-weight (NBW) and six IUGR newborn piglets were slaughtered within 2 to 4 h after birth to compare the effects of IUGR on the liver antioxidant capacity of newborn piglets. The results showed that compared with NBW piglets, IUGR piglets had a lower birth weight and liver relative weight; IUGR piglets had a higher serum malondialdehyde (MDA) level, liver MDA level and hydrogen peroxide (H2O2) level, and had a lower liver total antioxidant capacity (T-AOC) level and glutathione peroxidase (GSH-Px) activity; IUGR trended to increase serum alanine aminotransferase activity, aspartate aminotransferase activity, and H2O2 level, and trended to decrease liver total superoxide dismutase activity. In experiment 2, six NBW piglets, and 12 IUGR piglets weaned at 21 d of age were randomly divided into the NC group (NBW piglets fed with basal diet); IC group (IUGR piglets fed with basal diet), and IE group (IUGR piglets fed with basal diet plus 2 mg/kg EGF), and feeding for 14 d. Organ index, serum parameters, liver antioxidant capacity, and liver antioxidant-related genes expression were measured. The results showed that compared to the IC group, dietary EGF supplementation (IE group) significantly reduced serum malondialdehyde level and H2O2 level, and liver protein carbonyl (PC) level and 8-hydroxydeoxyguanosine level of piglets with IUGR; dietary EGF supplementation (IE group) significantly increased serum T-AOC level, liver T-AOC level and GSH-Px activity; dietary supplemented with EGF (IE group) enhanced liver Nrf2, NQO1, HO1, and GPX1 mRNA expression compared to IC group. Pearson's correlation analysis further showed that EGF can alleviate liver oxidative injury caused by IUGR and improve the performance of IUGR piglets. In conclusion, EGF exhibited potent protective effects on IUGR-induced liver oxidative injury, by activating the Nrf2 signaling pathway to mediate the expression of downstream antioxidant enzymes and phase II detoxification enzymes (NQO1 and HO1), thereby alleviating liver oxidative damage and promoting the growth performance of IUGR piglets.

The liver is an important metabolic and secretory organ in vertebrates, which plays an important role in the overall health of animals. Studies have shown that intrauterine growth retardation (IUGR) can cause liver injury in piglets, which is unfavorable to the growth and development of piglets. Epidermal growth factor (EGF) has antioxidant properties, but its effect on liver oxidative damage caused by IUGR remains uncertain. In the present study, we chose newborn piglets with low birth weight as the IUGR models to investigate whether IUGR could cause oxidative damage in the liver. Then, the diet supplemented with EGF was fed to IUGR piglets to study the effects of EGF supplementation on the liver antioxidant function of IUGR-weaned piglets. Results showed that IUGR caused serious damage to the liver of piglets, while dietary EGF supplementation could reverse the oxidative injury induced by IUGR to some extent. Therefore, this study confirmed that EGF has positive effects on the liver health of piglets with IUGR.

Asymptomatic Patient With Incarcerated Gravid Uterus Diagnosed in the Third Trimester: A Case Report of a Rare Potential Obstetric Emergency.

Incarcerated gravid uterus (IGU) is a rare condition that occurs when a retropositioned gravid uterus becomes entrapped within the pelvic cavity. Most patients present around the 17th week of pregnancy with symptoms such as pelvic fullness, urinary incontinence, abdominal pain, constipation, and vaginal bleeding. Rarely, patients are asymptomatic throughout pregnancy, leaving IGU undiagnosed and untreated. Here, we present an asymptomatic 26-year-old female who presented at 30 weeks of gestation with severe intrauterine growth retardation (IUGR) on serial obstetric ultrasounds. Further evaluation with ultrasound and MRI revealed an incarcerated uterus. This was complicated by severe fetal IUGR, abnormal biophysical profile, and oligohydramnios. This case highlights the importance of early diagnosis and treatment of IGU in order to prevent complications associated with the condition. Clinicians should be aware that, although uncommon, patients with IGU may be asymptomatic and that diagnosis should depend primarily on imaging findings rather than symptoms.

Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota, metabolic activity, and epithelial function.

BACKGROUND: Intrauterine growth retardation (IUGR) is one of the major constraints in animal production. Our previous study showed that piglets with IUGR are associated with abnormal bile acid (BA) metabolism. This study explored whether dietary BA supplementation could improve growth performance and colonic development, function, microbiota, and metabolites in the normal birth weight (NBW) and IUGR piglets. A total of 48 weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group): (i) NBW group, (ii) NBW + BA group, (iii) IUGR group, and (iv) IUGR + BA group. Samples were collected after 28 days of feeding. RESULTS: The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio, while decreased the plasma diamine oxidase (DAO) concentration in the NBW piglets (P < 0.05). Dietary BA supplementation to IUGR piglets decreased (P < 0.05) the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin, suggesting a beneficial effect on epithelial integrity. Moreover, dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance (P < 0.05), whereas Lactobacillus was the dominant genus in the colon. Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA, respectively, which was associated with the colonic function of IUGR piglets. Furthermore, dietary BA supplementation to IUGR piglets upregulated the expressions of CAT, GPX, SOD, Nrf1, IL-2, and IFN-γ in colonic mucosa (P < 0.05). CONCLUSIONS: Collectively, dietary BA supplementation could improve the colonic function of IUGR piglets, which was associated with increasing proportions of potentially beneficial bacteria and metabolites. Furthermore, BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

Prenatal immobility stress: Relationship with oxidative stress, inflammation, apoptosis, and intrauterine growth restriction in rats.

BACKGROUND: Prenatal stress is a significant risk factor affecting pregnant women and fetal health. In the present study, we aimed to investigate the effect of immobility stress at different periods of pregnancy on oxidative stress, inflammation, placental apoptosis and intrauterine growth retardation in rats. METHODS: Fifty adult virgin female Wistar albino rats were used. Pregnant rats were exposed to 6 h/day immobilization stress in a wire cage at different stages of pregnancy. Groups I and II (Day 1-10 stress group) were sacrificed on the 10th day of pregnancy, and Group III, Group IV (10-19th-day stress group), and Group V (1-19th-day stress group) were sacrificed on the 19th day of pregnancy. Inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-10 (IL-10), serum corticotropin-releasing hormone (CRH), and corticosterone levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the placenta were spectrophotometrically measured. Histopathological analyses of the placenta were evaluated by hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivity in placenta tissues were determined by the indirect immunohistochemical method. Placental apoptosis was determined by the TUNEL staining method. RESULTS: We found that the immobility stress during pregnancy significantly increased serum corticosterone levels. Our results showed that the immobility stress diminished the number and weight of fetuses in rats compared to the non-stress group. The immobility stress caused significant histopathological changes in the connection zone and labyrinth zone and increased placental TNF-α and caspase-3 immunoreactivity and placental apoptosis. In addition, immobility stress significantly increased the levels of pro-inflammatory IL-6 and MDA and caused a significant decrease in the levels of antioxidant enzymes such as SOD, CAT, and anti-inflammatory IL-10. CONCLUSIONS: Our data suggest that immobility stress causes intrauterine growth retardation by activating the hypothalamic-pituitary-adrenal axis and deteriorating placental histomorphology and deregulating inflammatory and oxidative processes.

Effects of Dietary Nano-Zinc Oxide Supplementation on Meat Quality, Antioxidant Capacity and Cecal Microbiota of Intrauterine Growth Retardation Finishing Pigs.

As nano-zinc oxide (Nano-ZnO), a new type of nanomaterial, has antioxidant and intestinal protection effects, we hypothesized that dietary Nano-ZnO could modulate poor meat quality, oxidative stress and disturbed gut microbiota in the finishing pig model of naturally occurring intrauterine growth retardation (IUGR). A total of 6 normal-born weight (NBW) and 12 IUGR piglets were selected based on birth weight. The pigs in the NBW group received a basal diet, and IUGR pigs were randomly divided into two groups and treated with basal diet and 600 mg/kg Nano-ZnO-supplemented diet. Dietary Nano-ZnO ameliorated IUGR-associated declined meat quality by lowering the drip loss48h, cooking loss, shearing force and MyHc IIx mRNA expression, and raising the redness (a*), peak area ratio of immobilized water (P22), sarcomere length and MyHc Ia mRNA expression. Nano-ZnO activated the nuclear factor erythroid 2-related factor 2-glutamyl cysteine ligase (Nrf2-GCL) signaling pathway by promoting the nuclear translocation of Nrf2, increasing the GCL activities, and mRNA and protein expression of its catalytic/modify subunit (GCLC/GCLM), thereby attenuating the IUGR-associated muscle oxidative injury. Additionally, the composition of IUGR pigs' cecal microbiota was altered by Nano-ZnO, as seen by changes in Shannon and Simpson indexes, the enhanced UCG-005, hoa5-07d05 gut group and Rikenellaceae RC9 gut group abundance. The UCG-005 and hoa5-07d05 gut group abundance were correlated with indicators that reflected the meat quality traits and antioxidant properties. In conclusion, Nano-ZnO improved the IUGR-impaired meat quality by altering water holding capacity, water distribution and the ultrastructure of muscle, activating the Nrf2-GCL signaling pathway to alleviate oxidative status and regulating the cecal microbial composition.

Effects of Equol Supplementation on Growth Performance, Redox Status, Intestinal Health and Skeletal Muscle Development of Weanling Piglets with Intrauterine Growth Retardation.

Animals with intrauterine growth retardation (IUGR) usually undergo injured postnatal growth and development during the early period after birth. Equol (Eq), an isoflavan produced by gut bacteria in response to daidzein intake, has various health benefits. Therefore, the objective of this study was to evaluate whether Eq supplementation can influence the growth performance, redox status, intestinal health and skeletal muscle development of weanling piglets with IUGR. A total of 10 normal-birth-weight (NBW) newborn female piglets and 20 newborn female piglets with IUGR were selected. After weaning at the age of 21 d, 10 NBW piglets and 10 IUGR piglets were allocated to the NBW group and IUGR group, respectively, and offered a basal diet. The other 10 IUGR piglets were allocated to the IUGR + Eq group and offered a basal diet with 50 mg of Eq per kg of diet. The whole trial lasted for 21 d. At the end of the feeding trial, all piglets were sacrificed for the collection of serum, intestinal tissues and skeletal muscles. Supplementation with Eq increased the average daily gain (ADG), average daily feed intake (ADFI), duodenal villus height to crypt depth ratio (V/C), jejunal villus height and V/C, but reduced the duodenal crypt depth in neonatal piglets with IUGR. Meanwhile, Eq supplementation elevated the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum and duodenum and the activity of SOD in the jejunum, but lowered malondialdehyde (MDA) content in the serum, jejunum and ileum of piglets with IUGR. In addition, supplementation with Eq reduced diamine oxidase (DAO) activity and the levels of D-lactate and endotoxin in serum, and the tumor necrosis factor-α (TNF-α) level in jejunum and ileum, whereas the concentration of serum immunoglobulin G (IgG) and the mRNA levels of intestinal barrier-related markers in jejunum and ileum of IUGR piglets were increased. Furthermore, supplementation with Eq elevated the percentage of fast-fibers and was accompanied with higher mRNA expression of myosin heavy chain IIb (MyHC IIb) and lower mRNA levels in MyHC I in the longissimus thoracis (LT) muscle of IUGR piglets. In summary, Eq supplementation can promote antioxidant capacity, maintain intestinal health and facilitate skeletal muscle development, thus resulting in the higher growth performance of IUGR piglets.

Dietary ferulic acid supplementation improves antioxidant capacity and lipid metabolism in liver of piglets with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) can result in early liver oxidative damage and abnormal lipid metabolism in neonatal piglets. Ferulic acid (FA), a phenolic compound widely found in plants, has many biological functions, such as anti-inflammation and anti-oxidation. Thus, we explored the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in newborn piglets with IUGR. In the study, 24 7-day-old piglets were divided into three groups: normal birth weight (NBW), IUGR, and IUGR + FA. The NBW and IUGR groups were fed formula milk as a basal diet, while the IUGR + FA group was fed a basal diet supplemented with 100 mg/kg FA. The trial lasted 21 days. The results showed that IUGR decreased absolute liver weight, increased transaminase activity, reduced antioxidant capacity, and disrupted lipid metabolism in piglets. Dietary FA supplementation enhanced absolute liver weight, reduced serum MDA level and ROS concentrations in serum and liver, markedly increased serum and liver GSH-PX and T-SOD activities, decreased serum HDL-C and LDL-C and liver NEFA, and increased TG content and HL activity in the liver. The mRNA expression related to the Nrf2-Keap1 signaling pathway and lipid metabolism in liver were affected by IUGR. Supplementing FA improved the antioxidant capacity of liver by down-regulating Keap1 and up-regulating the mRNA expression of SOD1 and CAT, and regulated lipid metabolism by increasing the mRNA expression level of Fasn, Pparα, LPL, and CD36. In conclusion, the study suggests that FA supplementation can improve antioxidant capacity and alleviate lipid metabolism disorders in IUGR piglets.