Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway.

BACKGROUND: Abnormal placental angiogenesis is an important cause of fetal intrauterine growth restriction (IUGR), but its underlying mechanisms and therapies remain unclear. Adenosine and its mediated signaling has been reported to be associated with the development of angiogenesis. However, whether the adenosine-related signaling plays a role in modulating angiogenesis in placenta and the IUGR pregnancy outcomes remains unclear. METHODS: The angiogenesis and adenosine signaling expressions in normal and IUGR placentas were detected in different species. And the role of adenosine in regulating IUGR pregnancy outcomes was evaluated using diet-induced IUGR mouse model. Molecular mechanisms underlying adenosine-induced angiogenesis were investigated by in vitro angiogenesis assays and in vivo Matrigel plug assays. RESULTS: Here, we demonstrated poor angiogenesis and low adenosine concentration and downregulated expression of its receptor A2a (ADORA2A [adenosine A2a receptor]) in IUGR placenta. Additionally, the beneficial effects of adenosine in improving IUGR pregnancy outcomes were revealed in a diet-induced IUGR mouse model. Moreover, adenosine was found to effectively improve adenosine signaling and angiogenesis in IUGR mice placenta. Mechanistically, by using angiogenesis assays in vitro and in vivo, adenosine was shown to activate ADORA2A to promote the phosphorylation of Stat3 (signal transducer and activator of transcription 3) and Akt (protein kinase B), resulting in increased Ang (angiogenin)-dependent angiogenesis. CONCLUSIONS: Collectively, this study uncovers an unexpected mechanism of promoting placental angiogenesis by adenosine-ADORA2A signaling and advances the translation of this signaling as a prognostic indicator and therapeutic target in IUGR treatment.

Effects of dietary supplementation of different levels of gamma-aminobutyric acid on reproductive performance, glucose intolerance, and placental development of gilts.

This study aimed to investigate the effects of dietary gamma-aminobutyric acid (GABA) supplementation on reproductive performance, glucose intolerance, and placental development of gilts during mid-late gestation. Based on the principle of backfat thickness consistency, 124 gilts at 65 d of gestation were assigned to three dietary groups: CON (basic diet, n = 41), LGABA (basic diet supplemented with 0.03% GABA, n = 42), and HGABA (basic diet supplemented with 0.06% GABA, n = 41). The litter performance, glucose tolerance, placental angiogenesis, and nutrients transporters were assessed. The LGABA group improved piglet vitality and placental efficiency and decreased area under the curve of glucose tolerance test compared to the CON group (P < 0.05). Meanwhile, the LGABA group enhanced placental vessel density, platelet endothelial cell adhesion molecule-1 levels and gene expression of fibroblast growth factor 18 (P < 0.05). Furthermore, LGABA showed an uptrend in glucose transporter type 1 mRNA level (P = 0.09). Taken together, this study revealed that the dietary supplementation of 0.03% GABA can improve piglet vitality, glucose intolerance, and placental development of gilts.

Glucose homeostasis and placental development are two key factors influencing reproductive performance of sows. Some studies have reported that gamma-aminobutyric acid (GABA) can improve glucose intolerance and cerebral angiogenesis in mice. Therefore, we hypothesized that GABA can improve reproductive performance, glucose intolerance, and placental development of gilts during mid-late gestation. In this study, gilts were randomly assigned into three groups: CON (basal diet), LGABA (basal diet supplemented with 0.03% GABA), and HGABA (basal diet supplemented with 0.06% GABA). Results showed that the LGABA group significantly improved the piglet viability, glucose intolerance, and placental development compared with the CON group. Therefore, GABA has a good prospect as a feed additive for gilts.

Maternal or post-weaning dietary fructo-oligosaccharide supplementation reduces stillbirth rate of sows and diarrhea of weaned piglets.

Fructo-oligosaccharides (FOS) are well-known prebiotics that have the potential to improve sow reproductive performance and increase piglet growth. However, previous studies were observed in sole FOS-supplemented diets of sows or weaned piglets and did not consider the sow-to-piglet transfer effect on the performance and diarrhea rate of weaned piglets. This study explores the effects of dietary FOS supplementation on the reproductive performance of sows, and the effects of FOS supplementation at different stages on the growth performance and diarrhea rate of weaned piglets. A split-plot experimental design was used with sow diet effect in the whole plot and differing piglet diet effect in the subplot. Fifty-two multiparous sows (223.24 ± 14.77 kg) were randomly divided into 2 groups (0 or 0.2% FOS). The experiment lasted from day 85 of gestation to day 21 of lactation. Reproductive performance, glucose tolerance, placental angiogenesis, and intestinal flora of sows were assessed. At weaning, 192 weaned piglets were grouped in 2 × 2 factorial designs, with the main effects of FOS supplemental level of sow diet (0 and 0.2%), and FOS supplemental level of weaned piglet diet (0 and 0.2%), respectively. The growth performance and diarrhea rate of the weaned piglets were analyzed during a 28-d experiment. Maternal dietary supplementation of FOS was shown to reduce the stillbirth and invalid piglet rates (P < 0.05), improve the insulin sensitivity (P < 0.05) and fecal scores (P < 0.05) of sows, increase the abundance of Akkermansia muciniphila (P = 0.016), decrease the abundance of Escherichia coli (P = 0.035), and increase the isovalerate content in feces (P = 0.086). Meanwhile, the placental angiogenesis marker CD31 expression was increased in sows fed FOS diet (P < 0.05). Moreover, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets (P < 0.05) and increased the content of short-chain fatty acids in feces (P < 0.05). Furthermore, only post-weaning dietary FOS supplementation could improve nutrient digestibility of weaned piglets (P < 0.05). Collectively, FOS supplementation in sows can reduce stillbirth rate, perinatal constipation, and insulin resistance, as well as improve placental vascularization barrier. Additionally, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets, but only FOS supplementation in piglets alone at weaning stage could improve their nutrient digestibility.

Dietary adenosine supplementation improves placental angiogenesis in IUGR piglets by up-regulating adenosine A2a receptor.

Abnormal placental angiogenesis is associated with the occurrence of intrauterine growth restriction (IUGR) in piglets, and effective treatment strategies against this occurrence remain to be explored. Adenosine has been reported to play an important role in angiogenesis, but its role in placental angiogenesis is still unknown. Here, we investigated the effect of dietary adenosine supplementation on IUGR occurrence in piglets by analyzing the role of adenosine in placental angiogenesis for Normal and IUGR piglets. Specifically, 88 sows were allotted to 2 treatments (n = 44) and fed a basal diet supplemented with 0% or 0.1% of adenosine from day 65 of gestation until farrowing, followed by collecting the placental samples of Normal and IUGR piglets, and recording their characteristics. The results showed that adenosine supplementation increased the mean birth weight of piglets (P < 0.05) and placental efficiency (P < 0.05), while decreasing the IUGR piglet rate (P < 0.05). Expectedly, the placenta for IUGR neonates showed a down-regulated vascular density (P < 0.05) and angiogenesis as evidenced by the expression level of vascular cell adhesion molecule-1 (VCAM1) (P < 0.05). Notably, dietary adenosine supplementation promoted angiogenesis (P < 0.05) both in the Normal and IUGR placenta. More importantly, the expression level of adenosine A2a receptor (ADORA2A) was lower (P < 0.05) in the IUGR placenta than in Normal placenta, whereas adenosine treatment could significantly increase ADORA2A expression, and also had an interaction effect between factors IUGR and Ado. Collectively, placentae for IUGR piglets showed impaired angiogenesis and down-regulated expression level of ADORA2A, while dietary adenosine supplementation could activate ADORA2A expression, improve the placental angiogenesis, and ultimately decrease the occurrence of IUGR in piglets.

Retinoic Acid-PPARα Mediates ß-Carotene Resistance to Placental Dysfunction Induced by Deoxynivalenol.

Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of ß-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% ß-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, ß-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid-peroxisome proliferator-activated receptor α signaling.

Cysteamine and N-Acetyl-cysteine Alleviate Placental Oxidative Stress and Barrier Function Damage Induced by Deoxynivalenol.

Sows are highly sensitive to deoxynivalenol (DON) and susceptible to reproductive toxicity caused by oxidative stress, but the potential mechanisms and effective interventions remain unclear. Here, we investigated the role of two antioxidants (cysteamine and N-acetyl-cysteine) in regulating the reproductive performance, redox status, and placental barrier function of sows and their potential mechanisms under DON exposure. Maternal dietary supply of antioxidants from day 85 of gestation to parturition reduced the incidence of stillbirths and low-birth-weight piglets under DON exposure. Moreover, the alleviation of DON-induced reproductive toxicity by dietary antioxidants was associated with the alleviation of placental oxidative stress, the enhancement of the placental barrier, and the vascular function of sows. Furthermore, in vivo and in vitro vascularized placental barrier modeling further demonstrated that antioxidants could reverse both DON transport across the placenta and DON-induced increase of placental barrier permeability. The molecular mechanism of antioxidant resistance to DON toxicity may be related to the signal transducer and activator of the transcription-3-occludin/zonula occludens-1 signaling pathway. Collectively, these results demonstrate the potential of antioxidants to protect the mother from DON-induced reproductive toxicity by alleviating placental oxidative stress and enhancing the placental barrier.

Dietary fiber supplementation during the last 50 days of gestation improves the farrowing performance of gilts by modulating insulin sensitivity, gut microbiota, and placental function.

Our previous study found dietary konjac flour (KF) supplementation could improve insulin sensitivity and reproductive performance of sows, but its high price limits its application in actual production. This study aimed to investigate the effects of supplementation of a cheaper combined dietary fiber (CDF, using bamboo shoots fiber and alginate fiber to partially replace KF) from the last 50 days of gestation to parturition on farrowing performance, insulin sensitivity, gut microbiota, and placental function of gilts. Specifically, a total of 135 pregnant gilts with a similar farrowing time were blocked by backfat thickness and body weight on day 65 of gestation (G65d) and assigned to 1 of the 3 dietary treatment groups (n = 45 per group): basal diet (CON), basal diet supplemented with 2% KF or 2% CDF (CDF containing 15% KF, 60% bamboo shoots fiber, and 25% alginate fiber), respectively. The litter performance, insulin sensitivity and glucose tolerance parameters, placental vessel density, and short-chain fatty acids (SCFAs) levels in feces were assessed. The gut microbiota population in gilts during gestation was also assessed by 16S rDNA gene sequencing. Compared with CON, both KF and CDF treatments not only increased the piglet birth weight (P < 0.05) and piglet vitality (P < 0.01) but also decreased the proportion of piglets with birth weight ≤ 1.2 kg (P < 0.01) and increased the proportion of piglets with birth weight ≥ 1.5 kg (P < 0.01). In addition, KF or CDF supplementation reduced fasting blood insulin level (P < 0.05), homeostasis model assessment-insulin resistance (P < 0.05), serum hemoglobin A1c (P < 0.05), and the level of advanced glycation end products (P < 0.05) at G110d, and increased the placental vascular density (P < 0.05) at farrowing. Meanwhile, KF or CDF supplementation increased microbial diversity (P < 0.05) and SCFAs levels (P < 0.05) in feces at G110d. Notably, the production cost per live-born piglet was lower in CDF group (¥ 36.1) than KF group (¥ 41.3). Overall, KF or CDF supplementation from G65d to farrowing could improve the farrowing performance of gilts possibly by improving insulin sensitivity, regulating gut microbiota and metabolites, and increasing placental vascular density, with higher economic benefits and a similar effect for CDF vs. KF, suggesting the potential of CDF as a cheaper alternative to KF in actual production.

Dietary konjac flour (KF) supplementation could improve insulin sensitivity and reproductive performance of sows, but its high price limits its application in actual production. This study investigated the impact of 2% konjac flour (KF) and 2% combined dietary fiber (CDF, containing 15% KF, 60% bamboo shoots fiber, and 25% alginate fiber) supplementation from the last 50 days of gestation to farrowing on farrowing performance, placental function, insulin sensitivity, and gut microbiota of gilts. Results indicated that KF or CDF supplementation during this time could improve the farrowing performance of gilts possibly by improving insulin sensitivity and gut microbiota, and increasing placental vascular density. Meanwhile, CDF could lower the production cost per live-born piglet and have a similar effect to KF, thus a cheaper alternative to KF in actual production. This study facilitates understanding the beneficial effects of KF and non-conventional dietary fiber sources on the reproductive performance of gilts.

Effects of dietary adenosine and adenosine 5'-monophosphate supplementation on carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs.

This study investigated the effects of adenosine (ADO) and adenosine 5'-monophosphate (AMP) supplementation on the growth performance, carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs. The pigs were allocated to three treatment groups: the control diet, 0.2%ADO diet, or 0.2%AMP diet. Compared with CON group (CON), both ADO and AMP groups increased in carcass straight length (P < 0.05) and decreased in drip loss (P < 0.05), while AMP group tended to increase in redness value (P = 0.05) and decreased in free amino acid content in longissimus thoracis (LT) muscle (P < 0.05). Additionally, ADO or AMP supplementation increased the ADO or AMP content in serum, adipose tissue, and LT muscle (P < 0.05), as well as the protein level of adenosine 2A receptor (A2a) in adipose tissue (P < 0.05). Moreover, both ADO and AMP groups showed an increase in the expression of lipolysis genes (ATGL and HSL) in adipose tissue (P < 0.05). Overall, AMP supplementation could improve meat quality, and ADO and AMP supplementation regulate the lipid metabolism of finishing pigs.

Konjac flour-mediated gut microbiota alleviates insulin resistance and improves placental angiogenesis of obese sows.

Our previous study revealed that dietary konjac flour (KF) could remodel gut microbiota and improve reproductive performance of sows, but its underlying mechanisms remain unclear. This experiment aimed to investigate how dietary KF improves reproductive performance of obese sows. Here, 60 sows were assigned into three groups according to their backfat thickness: normal backfat sows fed with control diet (CON-N), high backfat sows fed with control diet (CON-H) and high backfat sows fed with KF inclusion diet (KF-H). The characteristics of sows and piglets were recorded. Next, fecal microbiota transplantation (FMT) was performed on female mice, followed by recording the characteristics of female mice. The results showed that compared with CON-H group, KF-H group showed downtrend in stillbirth rate (P = 0.07), an increase in placental efficiency (P < 0.01) and average piglet weight (P < 0.01); coupled with a decrease in the values of homeostasis model assessment-insulin resistance (P < 0.01); as well as an increase in placental vascular density and protein expression of angiogenesis markers (P < 0.01). As expected, sows fed KF diets had improved abundance and diversity of gut microbiota. More importantly, compared with CON-H(FMT) group, KF-H(FMT) group showed improvement in reproductive performance and insulin sensitivity (P < 0.05), as well as an increase in placental labyrinth zone and protein expression of angiogenesis markers (P < 0.05). Furthermore, we found a content increase (P < 0.05) of SCFAs in both KF-H group sow and KF-H (FMT) group mice. Overall, KF supplementation could alleviate insulin resistance, promote placental angiogenesis, and ultimately improve the reproductive performance of sows via gut microbiota remodeling.

Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus.

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor-α) and abnormal maternal glucose metabolism in patients with GDM, and a high fermentable dietary fiber (HFDF; konjac) could reduce GDM development through gut flora-short-chain fatty acid-placental inflammation axis in GDM mouse model. Mechanistically, HFDF increases abundances of Lachnospiraceae and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high-fat diet-induced insulin resistance. Lachnospiraceae and butyrate have similar anti-GDM and anti-placental inflammation effects, and they can ameliorate placental function and pregnancy outcome effects probably by dampening placental immune dysfunction. These findings demonstrate the involvement of important placental inflammation-related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-flora-placenta axis.

Effects of dietary supplementation of gestating sows with adenosine 5'-monophosphate or adenosine on placental angiogenesis and vitality of their offspring.

Our previous study found that dietary nucleotide supplementation, including adenosine 5'-monophosphate (AMP), could increase AMP content in sow milk and promote piglet growth, but its effects on placental efficiency and piglet vitality remain unknown. This experiment aimed to investigate the effects of dietary AMP or its metabolite adenosine (ADO) supplementation on sow reproductive performance and placental angiogenesis. A total of 135 sows with a similar farrowing time were blocked by backfat and body weight (BW) at day 65 of gestation and assigned to one of three dietary treatment groups (n = 45 per treatment): basal diet, basal diet supplemented with 0.1% AMP or 0.1% ADO, respectively. Placental analysis and the characteristics of sows and piglets unveiled that compared with control (CON) group, AMP or ADO supplementation could improve sow placental efficiency (P < 0.05) and newborn piglet vitality (P < 0.05), increase piglet birth weight (P < 0.05), and reduce stillbirth rate (P < 0.05). More importantly, AMP or ADO supplementation could increase the contents of AMP, ADO, and their metabolites in placentae (P < 0.05). Meanwhile, AMP or ADO supplementation could also increase placental vascular density (P < 0.05) and the expression of vascular endothelial growth factor A (P < 0.05), as well as promote the migration and tube formation of porcine iliac artery endothelial cells (P < 0.05). Overall, maternal dietary AMP or ADO supplementation could increase their contents in the placenta, thereby improving placental angiogenesis and neonatal piglet vitality.

Placental angiogenesis regulates piglet growth and development. Adenosine 5ʹ-monophosphate (AMP), a breakdown product of adenosine triphosphate, can be further converted to adenosine with various biological activities. However, little is known about whether AMP supplementation favors piglet growth and development as well as placental angiogenesis. This study facilitates the understanding of the promoting effects of AMP supplementation on placental angiogenesis and farrowing performance.

UPLC-Orbitrap-MS/MS Combined With Biochemical Analysis to Determine the Growth and Development of Mothers and Fetuses in Different Gestation Periods on Tibetan Sow Model.

Pregnancy is a complex and dynamic process, the physiological and metabolite changes of the mother are affected by different pregnancy stages, but little information is available about their changes and potential mechanisms during pregnancy, especially in blood and amniotic fluid. Here, the maternal metabolism rules at different pregnancy stages were investigated by using a Tibetan sow model to analyze the physiological hormones and nutrient metabolism characteristics of maternal serum and amniotic fluid as well as their correlations with each other. Our results showed that amniotic fluid had a decrease (P < 0.05) in the concentrations of glucose, insulin and hepatocyte growth factor as pregnancy progressed, while maternal serum exhibited the highest concentrations of glucose and insulin at 75 days of gestation (P < 0.05), and a significant positive correlation (P < 0.05) between insulin and citric acid. Additionally, T4 and cortisol had the highest levels during late gestation (P < 0.05). Furthermore, metabolomics analysis revealed significant enrichment in the citrate cycle pathway and the phenylalanine/tyrosine/tryptophan biosynthesis pathway (P < 0.05) with the progress of gestation. This study clarified the adaptive changes of glucose, insulin and citric acid in Tibetan sows during pregnancy as well as the influence of aromatic amino acids, hepatocyte growth factor, cortisol and other physiological indicators on fetal growth and development, providing new clues for the normal development of the mother and the fetus, which may become a promising target for improving the well-being of pregnancy.

Dietary fibers with low hydration properties exacerbate diarrhea and impair intestinal health and nutrient digestibility in weaned piglets.

BACKGROUND: This study aimed to investigate the hydration properties of different-source fibrous materials by comparing their water-binding capacity (WBC), water swelling capacity (WSC), viscosity, and in vivo effects of selected samples on growth performance, nutrient digestibility, diarrhea, and intestinal health in weaned piglets. METHODS: A total of 13 commercially available fibrous materials were first compared in chemical composition and in vitro hydration property. Subsequently, 40 weaned piglets were randomized to five experimental dietary groups (8 piglets per group): control diet (a basal diet without dietary fiber, CON), basal diet supplemented with 5% microcrystalline cellulose (MCC), 5% wheat bran (WB), 5% Moringa oleifera leaf powder (MOLP), or 5% sugar beet pulp (SBP), followed by analyzing their growth performance and diarrhea rate in a 28-d experiment. After the feeding experiment, anaesthetized piglets were killed, and their intestinal and colon content or plasma samples were analyzed in nutrient digestibility, intestinal morphology, intestinal barrier, short-chain fatty acids (SCFAs), and bacterial population. RESULTS: In vitro studies showed low hydration properties for WB and MCC, while medium hydration properties for MOLP and SBP. In vivo studies indicated that compared with medium hydration property groups, low hydration property groups showed (1) exacerbated diarrhea, impaired intestinal health, and reduced apparent fecal digestibility of dry matter, gross energy, acid detergent fiber, and neutral detergent fiber; (2) decreased SCFAs concentration and relative levels of Lactobacillus and Bifidobacterium, but increased levels of Escherichia coli and Brachyspira hyodysenteriae in colon contents. Additionally, SBP showed optimal performance in reducing diarrhea and increasing SCFAs production. Correlation analysis revealed a positive correlation of fiber hydration properties with in vitro SCFAs production, and diarrhea index and nutrient digestibility were negatively and positively correlated with SCFAs levels in the colon contents of weaned piglets, respectively. CONCLUSIONS: Different-source dietary fibers varied in their hydration properties and impacts on diarrhea, microbial composition and SCFAs production in weaned piglets. WB and MCC could exacerbate diarrhea and impair nutrient digestibility, probably because their low hydration properties were detrimental to gut microbial homeostasis and fermentation. Our findings provide new ideas for rational use of fiber resources in weaned piglets.

Placental Angiogenesis in Mammals: A Review of the Regulatory Effects of Signaling Pathways and Functional Nutrients.

Normal placental development and proper angiogenesis are essential for fetal growth during pregnancy. Angiogenesis involves the regulatory action of many angiogenic factors and a series of signal transduction processes inside and outside the cell. The obstruction of placental angiogenesis causes fetal growth restriction and serious pregnancy complications, even leading to fetal loss and pregnancy cessation. In this review, the effects of placental angiogenesis on fetal development are described, and several signaling pathways related to placental angiogenesis and their key regulatory mediators are summarized. These factors, which include vascular endothelial growth factor (VEGF)-VEGF receptor, delta-like ligand 4 (DLL-4)-Notch, Wnt, and Hedgehog, may affect the placental angiogenesis process. Moreover, the degree of vascularization depends on cell proliferation, migration, and differentiation, which is affected by the synthesis and secretion of metabolites or intermediates and mutual coordination or inhibition in these pathways. Furthermore, we discuss recent advances regarding the role of functional nutrients (including amino acids and fatty acids) in regulating placental angiogenesis. Understanding the specific mechanism of placental angiogenesis and its influence on fetal development may facilitate the establishment of new therapeutic strategies for the treatment of preterm birth, pre-eclampsia, or intrauterine growth restriction, and provide a theoretical basis for formulating nutritional regulation strategies during pregnancy.

Inclusion of wheat aleurone in gestation diets improves postprandial satiety, stress status and stillbirth rate of sows.

This study investigated the effects of different amounts of wheat aleurone (WA) (0, 15%, 30%) inclusion in gestation diets on the reproductive performance, postprandial satiety, stress status and stereotypic behaviors of sows. A total of 84 Landrace × Yorkshire sows (parity 4.87 ± 1.32) at breeding were randomly allotted to one of the three isoenergetic and isonitrogenous dietary treatments based on parity and body weight. The results showed that, compared with the control (0), sows fed the WA diet had a higher serum concentration of peptide YY (PYY) (P < 0.05) and glucagon like peptide-1 (GLP-1) (P < 0.05) and a lower concentration of saliva cortisol (P < 0.01). Importantly, compared with the control group, only the 15% WA group had a higher concentration of the total antioxidant capacity (T-AOC) (P < 0.05), lower proportions of sitting (P = 0.05) and stillbirth rates (P < 0.01). Accordingly, the production cost per piglet born alive ($ 6.9 vs. $ 7.6) or per piglet born healthy ($ 7.4 vs. $ 7.9) declined in the 15% WA group versus the control group. Overall, 15% WA inclusion in gestation diets contributed to enhancing postprandial satiety, alleviating stress status and decreasing stillbirth rate of sows. This study provides a reference for the application of WA as a partial substitute for conventional feed ingredients to improve sows' reproductive performance.

Maternal supply of cysteamine alleviates oxidative stress and enhances angiogenesis in porcine placenta.

BACKGROUND: Oxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes in sow, but there are few satisfactory treatment strategies for these conditions. This study investigated the potential of cysteamine (CS) as an antioxidant protectant for regulating the reproductive performance, redox status, and placental angiogenesis of sows. METHODS: The placental oxidative stress status and vascular density of piglets with different birth weights: < 1.0 kg (low birth weight, LBW) and 1.4-1.6 kg (normal birth weight, NBW) were evaluated, followed by allotting 84 sows to four treatments (n = 21) and feeding them with a basal diet supplemented with 0, 100, 300, or 500 mg/kg of CS from d 85 of gestation to d 21 of lactation, respectively. Placenta, serum, and colostrum samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, the in vivo results were validated using porcine vascular endothelial cells (PVECs). RESULTS: Compared with the NBW placentae, the LBW placentae showed increased oxidative damage and were vulnerable to angiogenesis impairment. Particularly, H2O2-induced oxidative stress prompted intracellular reactive oxygen species generation and inhibited the tube formation and migration of PVECs as well as the expression of vascular endothelial growth factor-A (VEGF-A) in vitro. However, dietary CS supplementation can alleviate oxidative stress and improve the reproductive performance of sows. Specifically, compared with the control group, dietary 100 mg/kg CS could (1) decrease the stillbirth and invalid rates, and increase both the piglet birth weight in the low yield sows and the placental efficiency; (2) increase glutathione and reduce malondialdehyde in both the serum and the colostrum of sows; (3) increase the levels of total antioxidant capacity and glutathione in LBW placentae; (4) increase the vascular density, the mRNA level of VEGF-A, and the immune-staining intensity of platelet endothelial cell adhesion molecule-1 in the LBW placentae. Furthermore, the in vitro experiment indicated that CS pre-treatment could significantly reverse the NADPH oxidase 2-ROS-mediated inactivation of signal transducer and activator of transcription-3 (Stat3) signaling pathway induced by H2O2 inhibition of the proliferation, tube formation, and migration of PVECs. Meanwhile, inhibition of Stat3 significantly decreased the cell viability, tube formation and the VEGF-A protein level in CS pretreated with H2O2-cultured PVECs. CONCLUSIONS: The results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of LBW piglets during pregnancy, but CS supplementation at 100 mg/kg during late gestation and lactation of sows could alleviate oxidative stress and enhance angiogenesis in placenta, thereby increasing birth weight in low yield sows and reducing stillbirth rate. The in vitro data showed that the underlying mechanism for the positive effects of CS might be related to the activation of Stat3 in PVECs.

Effects of dietary supplementation of nucleotides from late gestation to lactation on the performance and oxidative stress status of sows and their offspring.

Increased metabolic burdens in breeding sows, which are induced by elevated systemic oxidative stress, could increase the need for nucleotides to repair lymphocyte DNA damage; however, de novo synthesis of nucleotides may be insufficient to cover this increased need. This study investigated the effects of dietary nucleotides on milk composition, oxidative stress status, and the reproductive and lactational performance of sows. Forty multiparous sows were assigned to 2 dietary treatments (Control group, and 1 g/kg Nucleotides group) based on a randomized complete block design using their BW at 85 d of gestation as a block. Sows from 2 groups were fed a restricted diet during gestation and ad libitum during lactation. The experiment lasted from 85 d of gestation to 21 d of lactation. The reproductive performance of sows and the growth performance of suckling piglets were measured. Oxidative stress parameters and milk components were also analysed. Data were analyzed using contrasts in the MIXED procedure of SAS. Sows in the Nucleotides group consumed more feed during the first week (P < 0.01) and from 1 to 21 d (P < 0.05) of lactation than those in Control group. Correspondingly, the litter weight gain of piglets showed a tendency to increase from cross-fostering to 9 d (P = 0.09) and from cross-fostering to 20 d (P = 0.10) in the Nucleotides group relative to the Control group. Additionally, the Nucleotides group was higher (P < 0.01) than the Control group in the concentrations of uridine 5'monophosphate, guanosine 5'monophosphate, inosine 5'monophosphate, adenosine 5'monophosphate and total nucleotides in milk. Furthermore, the Nucleotides group was higher (P < 0.01) than the Control group in the serum levels of total antioxidant capacity (P < 0.01) for sows at 109 d of gestation and glutathione peroxidase for weaning piglets, but lower at the levels of thiobarbituric acid-reactive substances (P < 0.05) in serum of weaning piglets. This study indicated that maternal dietary nucleotides could promote piglet growth, probably due to the higher lactational feed intake and higher concentration of nucleotides in the milk of sows, and lower oxidative stress for both sows and piglets.

Effects of Dietary Fiber Sources during Gestation on Stress Status, Abnormal Behaviors and Reproductive Performance of Sows.

Inclusion of fiber in gestation diets is a method for enhancing satiety and reducing abnormal behaviors in restricted feeding sows without providing excess energy. The purpose of this study was to use an in vitro-in vivo method to appraise the effects of two available unconventional dietary fiber resources during gestation on sows' physio-chemical properties of diets, postprandial satiety, performance, abnormal behaviors, stress status and lactation feed intake under three different dietary treatments: control diet (CON diet), 5% resistant starch diet (RS diet), and 5% fermented soybean fiber diet (FSF diet) with a total of 78 (average parity 5) Landrace × Yorkshire sows. Results showed that swelling capacity was higher in the RS diet than in the CON or FSF diet. Meanwhile, the 48 h cumulative gas production and the final asymptotic gas volume after in vitro fermentation of gestation diets showed an increased trend (p = 0.07, p = 0.09, respectively) in the RS diet versus the CON or FSF diets. While the sows' litter size, body weight, backfat or weaning-to-estrus interval were not affected (p > 0.05) by the three treatments during gestation, the RS group showed a decline in stillbirth number (p < 0.05) and stillbirth rate (p < 0.01) relative to the other two groups. Meanwhile, the proportion of standing was lower while the sow's serum concentrations of PYY (peptide YY) and GLP-1 (glucagon-like peptide-1) were higher (p < 0.05) on day 70 of gestation in the RS group than in the CON or FSF group. Compared with the CON group, the RS group showed a downward tendency (p = 0.07) in the sows' plasma cortisol concentration on day 70 of gestation. A comparison of oxidative and antioxidative indicators revealed an increase in the sows' serum FRAP (ferric ion reducing antioxidant power) (p < 0.05) and a decrease of protein carbonyl (p < 0.05) on day 109 of gestation in the RS or FSF group versus the CON group. Overall, inclusion of 5% RS with greater swelling capacity in the gestation diet contributed to enhancing the postprandial satiety, alleviating the stress status, reducing the abnormal behaviors and thus lowering the stillbirth rate of sows.