The rhizomes of Atractylodes macrocephala Koidz improve gastrointestinal health and pregnancy outcomes in pregnant mice via modulating intestinal barrier and water-fluid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Baizhu (BZ) is the dried rhizome of Atractylodes macrocephala Koidz (Compositae), which invigorates the spleen, improves vital energy, stabilizes the fetus, and is widely used for treating spleen deficiency syndrome. However, the impact of BZ on gastrointestinal function during pregnancy remains unexplored. AIM OF THE STUDY: This study elucidated the ameliorative effects of BZ on gastrointestinal health and pregnancy outcomes in pregnant mice with spleen deficiency diarrhea (SDD). METHODS: To simulate an irregular human diet and overconsumption of cold and bitter foods leading to SDD, a model of pregnant mice with SDD was established using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, general indicators and diarrhea-related parameters were measured. Gastric and intestinal motility (small intestinal propulsion and gastric emptying rates) were evaluated. Serum motilin (MTL), ghrelin, growth hormone (GH), gastrin (Gas), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), chorionic gonadotropin ß (ß-CG), progesterone (P), and estradiol (E2) were quantified using an enzyme-linked immunosorbent assay. Pathological changes were examined by hematoxylin and eosin staining (H&E) and alcian blue periodic acid Schiff staining (AB-PAS). Immunohistochemistry and immunofluorescence were used to measure the expression levels of the intestinal barrier and water metabolism-related proteins in colonic tissues. The pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, small size, average fetal weight, and body length of fetal mice were calculated. RESULTS: The results showed that BZ significantly improved general indicators and diarrhea in pregnant mice with SDD, increased gastric emptying rate and small intestinal propulsion rate, elevated the levels of gastrointestinal hormones (AMS, ghrelin, GH, and Gas) in the serum, and reduced lipid levels (TC and LDL-c). It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin, claudin-1, ZO-1, AQP3, AQP4, and AQP8 in colonic tissues, downregulating the mRNA and protein expression levels of claudin-2, thereby alleviating intestinal barrier damage and regulating the balance of water and fluid metabolism. BZ also held the levels of pregnancy hormones (ß-CG, P, and E2) in the serum of pregnant mice with SDD. Moreover, it increased the pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, litter size, average fetal weight, and body length of fetal mice. These findings indicate that BZ can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

A case-control retrospective study for the effect of Shoutai Wan on IVF-ET pregnancy outcome.

It has a long history of preventing and treating disease using traditional Chinese medicine (TCM). In recent years, it has been widely used in adjuvant therapies of in vitro fertilization - embryo transfer (IVF-ET) in China. To observe the effect and safety of Shoutai Wan on pregnancy outcomes after IVF-ET. A total of 352 patients who underwent IVF-ET from July 1, 2020 to June 30, 2021. The participants who only received routine luteal support during clinical pregnancy of FET were defined as the control group, and others who received TCM decoction Shoutai Wan for prevention of miscarriage and routine luteal support were defined as the Chinese medicine protection Shoutai Wan group (St group). This project has been approved by the Ethics Committee of Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine (Approval NO: 2023-0305). The results of this retrospective cohort study revealed that Shoutaiwan combined with luteal support treatment can significantly decreased the miscarriage rate in pregnancy undergoing IVF-FET compared to the group accepted only luteal support treatment (P = .001). Meanwhile, St during pregnancy did not affect fetal birth weight (P = .354), and there was no adverse event in the St group reported, which confirmed the safety of TCM for fetus protection during pregnancy. This study not only provides evidences for the clinical administration of Shoutai Wan in IVF-ET, but also provides a novel direction for basic research into the subsequent innovative application of TCM.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

[Effect of Yunkang Oral Solution on pregnant mice with spleen deficiency syndrome].

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin ß(ß-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(ß-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

OECD 414 supplementary prenatal developmental toxicity study of sodium molybdate dihydrate in the rat and benchmark dose evaluation.

In a continuing investigation of the potential for reproductive and developmental toxicity of molybdenum (Mo), consequent to the previous published OECD studies [1,2] and as directed by the European Chemicals Agency [3], a supplemental rat GLP-compliant Prenatal Developmental Toxicity (PNDT) study was conducted to investigate higher dose levels of sodium molybdate dihydrate (SMD) in an identical study design (OECD 414)[4] to Murray et al. 2014a [1], at dietary concentrations calculated to provide target Mo levels of 80 and 120 mg/kg bw/day (the maximum-tolerated dose). There was no effect on post-implantation loss, litter size, sex ratio or the incidence of external, visceral or skeletal fetal malformations or variations. Fetal weight was reduced proportionate to maternal dose. Minimal differences observed in the ossification status of some extremities of fetuses from females receiving 120 mg Mo/kg bw/day were confirmed as transient by skeletal examination of PND 21 pups from a further group of females receiving the same dose regime. There was no evidence of copper depletion in serum, placenta or liver. A benchmark dose evaluation using continuous and dichotomous approaches by combining the fetal body weight data from this study and the previous study determined that the BMD05 ranged from 47 to 57 mg Mo/kg bw/day, depending on the modelling approach and the BMDL05 estimates ranged from 37 to 47 mg Mo/kg bw/day. These levels are considered a more statistically robust point of departure for risk assessment for reproductive effects than the established NOAEL of 40 mg Mo/kg bw/day.

Induction of labour at or near term for suspected fetal macrosomia.

BACKGROUND: Women with a suspected large-for-dates fetus or a fetus with suspected macrosomia (birthweight greater than 4000 g) are at risk of operative birth or caesarean section. The baby is also at increased risk of shoulder dystocia and trauma, in particular fractures and brachial plexus injury. Induction of labour may reduce these risks by decreasing the birthweight, but may also lead to longer labours and an increased risk of caesarean section. OBJECTIVES: To assess the effects of a policy of labour induction at or shortly before term (37 to 40 weeks) for suspected fetal macrosomia on the way of giving birth and maternal or perinatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016), contacted trial authors and searched reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials of induction of labour for suspected fetal macrosomia. DATA COLLECTION AND ANALYSIS: Review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information. For key outcomes the quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included four trials, involving 1190 women. It was not possible to blind women and staff to the intervention, but for other 'Risk of bias' domains these studies were assessed as being at low or unclear risk of bias. Compared to expectant management, there was no clear effect of induction of labour for suspected macrosomia on the risk of caesarean section (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.76 to 1.09; 1190 women; four trials, moderate-quality evidence) or instrumental delivery (RR 0.86, 95% CI 0.65 to 1.13; 1190 women; four trials, low-quality evidence). Shoulder dystocia (RR 0.60, 95% CI 0.37 to 0.98; 1190 women; four trials, moderate-quality evidence), and fracture (any) (RR 0.20, 95% CI 0.05 to 0.79; 1190 women; four studies, high-quality evidence) were reduced in the induction of labour group. There were no clear differences between groups for brachial plexus injury (two events were reported in the control group in one trial, low-quality evidence). There was no strong evidence of any difference between groups for measures of neonatal asphyxia; low five-minute infant Apgar scores (less than seven) or low arterial cord blood pH (RR 1.51, 95% CI 0.25 to 9.02; 858 infants; two trials, low-quality evidence; and, RR 1.01, 95% CI 0.46 to 2.22; 818 infants; one trial, moderate-quality evidence, respectively). Mean birthweight was lower in the induction group, but there was considerable heterogeneity between studies for this outcome (mean difference (MD) -178.03 g, 95% CI -315.26 to -40.81; 1190 infants; four studies; I2 = 89%).  For outcomes assessed using GRADE, we based our downgrading decisions on high risk of bias from lack of blinding and imprecision of effect estimates. AUTHORS' CONCLUSIONS: Induction of labour for suspected fetal macrosomia has not been shown to alter the risk of brachial plexus injury, but the power of the included studies to show a difference for such a rare event is limited. Also antenatal estimates of fetal weight are often inaccurate so many women may be worried unnecessarily, and many inductions may not be needed. Nevertheless, induction of labour for suspected fetal macrosomia results in a lower mean birthweight, and fewer birth fractures and shoulder dystocia. The observation of increased use of phototherapy in the largest trial, should also be kept in mind. Findings from trials included in the review suggest that to prevent one fracture it would be necessary to induce labour in 60 women. Since induction of labour does not appear to alter the rate of caesarean delivery or instrumental delivery, it is likely to be popular with many women. In settings where obstetricians can be reasonably confident about their scan assessment of fetal weight, the advantages and disadvantages of induction at or near term for fetuses suspected of being macrosomic should be discussed with parents. Although some parents and doctors may feel the evidence already justifies induction, others may justifiably disagree. Further trials of induction shortly before term for suspected fetal macrosomia are needed. Such trials should concentrate on refining the optimum gestation of induction, and improving the accuracy of the diagnosis of macrosomia.

Pre-natal dietary imbalance of folic acid and vitamin B12 deficiency adversely impacts placental development and fetal growth.

INTRODUCTION: The common practice of supplementing folic acid during pregnancy and the absence of such guidelines for vitamin B12 lead to an imbalance of these vitamins, especially in developing countries like India, where many women are vitamin B12 deficient. METHODS: The present study was designed to explore the effect of low vitamin B12 in combination with different levels of folic acid in the parental diet on fetal growth parameters and maternal reproductive performance in a transgenerational manner. The reversibility of these effects was studied by shifting the mice to a regular diet in the F1 generation in the case of transient groups and continued on the same diet in the sustained groups after the dietary exposure in the F0 generation. RESULTS: Vitamin B12 deficiency and different levels of folic acid resulted in the decreased placental and fetal weight of the F1 generation. Surprisingly, a decreased placental weight, low fetal weight, and reduced crown-rump length and head circumference were observed in F2 fetuses of vitamin B12 deficient with folate over-supplemented (BDFO) transient group, i.e. when F1 mice were shifted to normal diet conditions. Reduced follicles in ovaries and alteration in placental pathology in all the F0 groups and BDFO of the F1 transient group were also seen. DISCUSSION: Overall, the study revealed that dietary imbalance of vitamin B12 and folic acid, particularly B12 deficiency with over-supplemented folic acid, negatively affects placental and fetal development and maternal reproductive performance. Such effects are passed on to the next generation too.

The association between first-trimester omega-3 fatty acid supplementation and fetal growth trajectories.

BACKGROUND: Prenatal omega-3 fatty acid supplementation, particularly docosahexaenoic acid and eicosapentaenoic acid, has been associated with greater birthweight in clinical trials; however, its effect on fetal growth throughout gestation is unknown. OBJECTIVE: This study aimed to examine the association between first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation and growth trajectories of estimated fetal weight and specific fetal biometrics measured longitudinally from the second trimester of pregnancy to delivery. STUDY DESIGN: In a multisite, prospective cohort of racially diverse, low-risk pregnant women, we used secondary data analysis to examine fetal growth trajectories in relation to self-reported (yes or no) first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation. Fetal ultrasonographic measurements, including abdominal circumference, biparietal diameter, femur length, head circumference, and humerus length, were measured at enrollment (8-13 weeks) and up to 5 follow-up visits. Estimated fetal weight and head circumference-to-abdominal circumference ratio (a measure of growth symmetry) were calculated. Fetal growth trajectories were modeled for each measure using a linear mixed model with cubic splines. If significant differences in fetal growth trajectories between groups were observed (global P<.05), weekly comparisons were performed to determine when in gestation these differences emerged. Analyses were adjusted for maternal sociodemographics, parity, infant sex, total energy consumption, and diet quality score. All analyses were repeated using dietary docosahexaenoic acid and eicosapentaenoic acid intake, dichotomized at the recommended cutoff for pregnant and lactating women (≥0.25 vs <0.25 g/d), among women who did not report supplement intake in the first trimester of pregnancy were repeated. RESULTS: Among 1535 women, 143 (9%) reported docosahexaenoic acid and eicosapentaenoic acid supplementation in the first trimester of pregnancy. Overall, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with statistically significant differences (P-value <.05) in fetal growth trajectories during pregnancy. Specifically, estimated fetal weight was larger among women with docosahexaenoic acid and eicosapentaenoic acid supplementation than among those without supplementation (global P=.028) with significant weekly differences in median estimated fetal weight most apparent between 38 to 41 weeks of gestation (median estimated fetal weight difference at 40 weeks of gestation, 114 g). Differences in fetal growth trajectories for abdominal circumference (P=.003), head circumference (P=.003), and head circumference-to-abdominal circumference ratio (P=.0004) were also identified by supplementation status. In weekly comparisons, docosahexaenoic acid and eicosapentaenoic acid supplement use was associated with larger median abdominal circumference (changed from 2 to 9 mm) in midpregnancy onward (19 to 41 weeks), larger median head circumference between 30 to 33 weeks of gestation, and smaller median head circumference-to-abdominal circumference ratio in the second and third trimesters of pregnancy. There was no specific weekly difference in fetal femur length or humerus length by docosahexaenoic acid and eicosapentaenoic acid supplementation. First-trimester dietary sources of docosahexaenoic acid and eicosapentaenoic acid among women with no first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation (n=1392) were associated with differences in fetal biparietal diameter (P=.043), but not other metrics of fetal growth. At the recommended dietary docosahexaenoic acid and eicosapentaenoic acid levels compared with below-recommended levels, biparietal diameter was larger between 38 to 41 weeks of gestation. CONCLUSION: In this racially diverse pregnancy cohort, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with significant increases in fetal growth, specifically greater estimated fetal abdominal circumference in the second and third trimesters of pregnancy.

Efecto de la suplementación del zinc sobre el peso fetal en ratas diabéticas gestadas / Effect of zinc supplementation on fetal weight in pregnant diabetic rats

RESUMEN Introducción: La relación entre la deficiencia de Zn y la elevada incidencia de alteraciones en el crecimiento intrauterino en la diabetes materna aún no se ha dilucidado. En la literatura consultada no existen reportes del efecto de la suplementación con el micronutriente sobre el crecimiento fetal en modelos de diabetes con hiperglucemias moderadas. Objetivo: Determinar el efecto sobre el peso fetal de la suplementación con zinc a ratas con diabetes moderada durante la gestación. Métodos: Se utilizó un modelo de diabetes moderada inducida en ratas Wistar al segundo día de nacidas por inducción subcutánea con estreptozotocina (100mg/kg-pc). En la adultez las ratas sanas y diabéticas fueron apareadas con machos sanos. Según correspondiera recibieron durante 20 días de gestación un suplemento de sulfato de zinc (50mg/kg). Se estudiaron 395 fetos de cuatro grupos: fetos de ratas sanas sin suplemento, de ratas sanas suplementadas, de ratas diabéticas sin suplemento y de ratas diabéticas suplementadas. Los fetos se clasificaron en pequeños (PEG), adecuados (AEG) y grandes (GEG) para la edad gestacional. Resultados: La descendencia de las ratas diabéticas suplementadas mostró valores del peso fetal similares a ambos grupos sanos al término de la gestación, presentando menor porcentaje de fetos PEG y GEG, así como mayor porcentaje de AEG respecto al grupo diabético no suplementado. Conclusiones: La suplementación con Zn durante la gestación a ratas diabéticas con hiperglucemias moderadas causó efectos positivos sobre su descendencia al aumentar el porcentaje de fetos con peso adecuado.

ABSTRACT Introduction: the relationship between Zn deficiency and the high incidence of abnormal intrauterine growth in maternal diabetes has not yet been elucidated. There are no reports in the consulted literature of the effect of micronutrient supplementation on fetal growth in models of diabetes with moderate hyperglycemia. Objective: to determine the effect of zinc supplementation on fetal weight in rats with moderate diabetes during pregnancy. Methods: a model of mild diabetes was used in Wistar rats on the second day of birth by subcutaneous streptozotocin induction (100mg/kg-bw). As adults, healthy and diabetic rats were mated with healthy males. As appropriate, they received a zinc sulfate supplement (50mg/kg) during 20 days of gestation. A number of 395 fetuses from four groups were studied: fetuses from healthy rats without supplementation, from healthy rats supplemented, from diabetic rats without supplementation and from diabetic rats supplemented. Fetuses were classified as small (SGA), adequate (AGA), and large (LGA) for gestational age. Results: the offspring of the supplemented diabetic rats showed similar fetal weight values to both healthy groups at the end of pregnancy, having a lower percentage of SGA and LGA fetuses, as well as a higher percentage of AGA compared to the non-supplemented diabetic group. Conclusions: Zn supplementation during pregnancy in diabetic rats with moderate hyperglycemia had positive effects on their offspring by increasing the percentage of fetuses with adequate weight.

Maternal Exposure to Oxidized Soybean Oil Impairs Placental Development by Modulating Nutrient Transporters in a Rat Model.

INTRODUCTION: As an exogenous food contaminant, dietary oxidized lipid impairs growth and development, and triggers chronic diseases in humans or animals. This study explores the effects of soybean oil with different oxidative degree on the placental injury of gestational rats. METHODS AND RESULTS: Thirty-two female adult rats are randomly assigned to four groups. The control group is fed the purified diet with fresh soybean oil (FSO), and the treatment groups are fed purified diets with lipid content replaced by oxidized soybean oil (OSO) at 200, 400, and 800 mEqO2 kg-1 from conception until delivery. On day 20 of gestation, OSO decreased placental and embryonic weights as the oxidative degree increased linearly and quadratically. The expression of Bax showed a linear increase, and Bcl-2 decreased as the oxidative degree increased. The expression of Fosl1 and Esx1 is linearly and quadratically decreased in OSO-treated groups than FSO group. OSO decreased the level of IL-10 but increased expression of IL-1ß in placenta and plasma. OSO remarkably upregulates levels of Fatp1 and Glut1 and decreases expression of Snat2 and Glut3. CONCLUSION: OSO aggravates placental injury by modulating nutrient transporters and apoptosis-related genes, impedes placental growth and development, and ultimately leads to the decrease of fetal weight.

Role of Heat Shock Protein 70 (HSP-70) after Giving Nanoherbal Haramonting (Rhodomyrtus tomentosa) in Preeclamptic Rats.

BACKGROUND AND OBJECTIVE: Haramonting (Rhodomyrtus tomentosa) is an alternative herb to improve health because it has many biological activities and antioxidant. HSP-70 levels as biomarkers of preeclampsia affected the anti-apoptosis of damaged cells in the placenta. This study aimed to evaluate the role of HSP-70 expressions by investigating whether effect haramonting leaves in PE rats. MATERIALS AND METHODS: The study design was control (C): pregnant rats without treatment, PE: Preeclamptic rats, PE+E: PE rats were given 1 mL EVOO kg-1 b.wt./day orally (pregnancy 13-19), PE+H: PE rats were given nano herbal haramonting 100 mg kg-1 b.wt. (pregnancy 13-19 days). PE+E+H: PE rats were given EVOO 0.5 mL kg-1 b.wt. and nano herbal haramonting 50 mg kg-1 b.wt. (pregnancy 13-19 day). Surgery was performed by taking blood from the heart for the SGOT/SGPT parameters, creatinine and HSP70. RESULTS: A significant difference was observed in all groups with the value p<0.0001 and HSP-70 Expressions affect in preeclamptic rats after given this herbal. The value of SGOT, SGPT and creatinine can affect preeclamptic rats and can be as a biomarker of preeclampsia. A significant difference also in fetus weight (p<0.01) but an insignificant difference in placental weight (p>0.05). CONCLUSION: These findings indicate that Nano herbal haramonting and EVOO possess antioxidative effects and a promising drug for the future in the treatment of preeclampsia.

Ouabain regulates kidney metabolic profiling in rat offspring of intrauterine growth restriction induced by low-protein diet.

AIMS: Intrauterine growth restriction (IUGR) can increase the risk of hypertension and kidney disease at adulthood due to fetal programming. In our previous study, we found that supplementation with low concentration of ouabain during pregnancy could restore glomerulus numbers at birth, rescuing kidney development. However, the metabolic pattern of kidney in IUGR offspring and the effect of ouabain have not been evaluated. MAIN METHODS: In this study, based on GC-MS and LC-MS platforms, we used the protein restriction rat model to explore the molecular mechanisms of kidney damage induced by IUGR and the protective effect of ouabain. KEY FINDINGS: The results showed that malnutrition could induce IUGR in rat offspring at the 20th gestational day but ouabain treatment could partially reverse the body and kidney weight loss. Ouabain treatment could upregulate arginine, N-acetylornithine and carbamoyl phosphate as well as adenine nucleotide and guanine nucleotide downregulated by low-protein diet. Moreover, six metabolites were identified to be significantly correlated with fetal kidney weight, with 3 metabolites involved in arginine metabolism (arginine, N-acetylornithine, urea) and UDP-glucuronate correlated positively, while lysine and anthranilate correlated negatively. SIGNIFICANCE: The results suggested that the underlying mechanism of ouabain against renal maldevelopment involved the metabolic regulation, particularly the arginine metabolism, which played an important role in the development of fetal kidney.

A pilot study on investigating the role of Salvia miltiorrhiza in fetal growth restriction.

To date there is no effective treatment for pregnancies complicated by fetal growth restriction (FGR). Salvia miltiorrhiza, a traditional Chinese herb has been shown to promote blood flow and improve microcirculatory disturbance. In this pilot study, we evaluated whether S. miltiorrhiza can potentially become a possible therapy for FGR. Nineteen pregnant women with FGR were treated with S. miltiorrhiza and ATP supplementation for an average of 7 days, and 17 cases received ATP supplementation as controls. The estimated fetal weights (EFWs) were measured by ultrasound after treatment, and the birthweights were recorded after birth. After treatment with S. miltiorrhiza, 7 (37%) FGR cases showed an increase in EFW to above the 10th percentile, compared with 4 (23%) FGR cases in controls (odds ratio: 1.896, 95% confidence limits (CLs): 0.44-8.144). At delivery, 10 (53%) FGR cases in the treatment group delivered babies with a birthweight above the 10th percentile, compared with 6 (35%) FGR cases in the control group (odds ratio: 2.037, 95% CL: 0.532-7.793); 80 or 64% FGR cases in the treatment group showed an increase in fetal abdominal circumference (AC) or biparietal diameter (BPD) above the 10th percentile before delivery. While 44 or 30% FGR cases in the control group showed an increase in AC or BPD. No improvement of head circumference (HC) or femur length (FL) was seen. These pilot data suggest the need for multicenter randomized clinical trials on the potential of S. miltiorrhiza to improve perinatal outcome in pregnant women complicated by FGR.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

KEY POINTS: Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. ABSTRACT: Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult-onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PaO2 and SaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

The Impact of Scientific and Technical Training on Improving Databases' Adequacy for Fetal Growth Chart Development in Limited-Resource Settings: A Case Study in the Province of South Kalimantan, Indonesia.

OBJECTIVES: To assess the impact of scientific and technical training on midwives' abilities in collecting and recording the key performance indicators for fetal growth chart development in limited-resource settings. METHODS: A descriptive design was used to describe midwives' abilities in timely collecting and recording the minimum data required to estimate fetal weight and develop fetal growth chart. The study was conducted among 19 urban and rural midwives in South Kalimantan, Indonesia, between April 2016 and October 2017. The training provided access to antenatal care information on 4,946 women (retrospective cohort study) and 381 women (prospective cohort study). RESULTS: The average amount of recorded antenatal care data on the key performance indicators of fetal growth assessment has been significantly improved (from 33.4% to 89.1%, p-value < 0.0005) through scientific and technical training. CONCLUSIONS: Scientific knowledge and technical abilities have enabled midwives to timely record routine data of the key performance indicators for fetal growth surveillance. Access to this information is vital during different stages of pregnancy. The information can be utilised as evidence-based guidelines to assess fetal risks through fetal weight estimation and to develop fetal growth chart that is currently not available in Indonesian primary healthcare systems.

Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress.

Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible.

Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone.

Background Genistein was reported to adversely influence fetal development although this is yet to be fully understood as a mechanism. Methods In this study, pregnant rats were divided into control (Cont.) and genistein force-fed (2-mg/kg and 4-mg/kg) groups. Each group was divided further into five subgroups: GD-0, GD-6, GD-13, GD-18, and GD-20 based on the terminal gestational day (GD). On the respective terminal GD, the rats were sacrificed and blood samples and amniotic fluid were carefully collected and separated and placenta homogenates were prepared. These samples were evaluated for oxidative stress and inflammatory reaction. The weights of embryonic implant and placenta tissue were also recorded. Heat shock protein (Hsp) (60 and 90), corticosterone, and oxidative stress biomarkers were determined in all the samples. Results Fetal and placental weights in all genistein-exposed groups were significantly decreased. A fluctuation in the level of the Hsp was recorded with a significant decrease recorded in Hsp90 level in the placenta and amniotic fluid towards GD-20 along with a concomitant increase in the corticosterone level in the amniotic fluid in all genistein groups compared to control. Maternal serum at GD-18 and GD -20 recorded a significant increase in antioxidant level (SOD, GSH, CAT) in all genistein-exposed groups. However, these antioxidants were significantly reduced in the placenta and the amniotic fluid compared to control. Conclusions Genistein enhances the placenta function in attenuating the risk of oxidative stress in the amniotic fluid and deferentially suppressed inflammatory activities in the placenta during early gestation and towards late gestation period.

Potential Interference of Oil Vehicles on Genital Tubercle Development during the Fetal Period in ICR Mice.

Corn oil, sesame oil, and 10% ethanol in corn oil are commonly used as dosing vehicles in toxicology studies. Since these vegetable oils contain bioactive compounds, it is important for toxicology studies to characterize the toxicities of the dosing vehicles themselves. It has been recently proposed that the width of the genital tubercle (GT), the dorsal-ventral length (D-V length) of the GT, and urethral tube closure in mouse fetuses can be used as novel markers for monitoring sexual development in mice. However, how these parameters are influenced by the dosing vehicles themselves remains unclear. Therefore, we evaluated the effects of corn oil, sesame oil, and 10% ethanol in corn oil on GT width, D-V length, and GT morphology in ICR mice. Our results showed that all three vehicles influenced GT width and D-V length, but not GT morphology, suggesting that the effects of dosing vehicles themselves might need to be considered when GT width or D-V length is used as a parameter to evaluate the effects of chemicals on GT development.

Embryo-fetal development studies with the dietary supplement vinpocetine in the rat and rabbit.

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child-bearing potential. Vinpocetine is a semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6-20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose-dependent increases in postimplantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose-dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in postimplantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine.

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity.

Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites and gene expression were measured. HF feeding significantly (P<.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P<.05) glucose transporter 1 and fatty acid transport protein 1 expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P<.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at midgestation and improved biomarkers of placental macronutrient homeostasis.