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28 Serum 25-OH D3 concentration changes in sows as a result of 25-OH D3 addition and mineral source 25-OH D3添加和矿物质来源对母猪血清25-OH D3浓度的影响
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.022
Bradley Lawrence, Jesus Acosta, Eric Myers, Chelsie Foran, Jon Bergstrom, Hans H Stein, Su A Lee, Andrea P Mallea, Deana Hancock
: Introduction Vitamin D is essential for growth and development including processes beyond those associated with bone. Vitamin D status can be low in reproducing sows. The vitamin D receptor is a Zn dependent receptor. Thus available mineral may be necessary to optimize vitamin D status. Objective Assess impact of mineral source fed during gestation and lactation on sow serum 25-OH D3 concentration. Methods Thirty-two multiparous sows (16 reps/treatment) were fed 100 ppm Zn, 20 ppm Cu and 40 ppm Mn either solely in the hydroxy form (ITM), or, as a 50:50 blend of metal methionine hydroxy analogue bis-chelate minerals and ITM (MHAC:ITM). All diets were supplemented with 50 mcg/kg 25-OH D3 and 1,000 FTU/kg phytase. Sows had not previously received 25-OH D3. Serum samples were obtained at insemination, gestation d-103, and 21-d post-farrow and analyzed for 25-OH D3 concentration. Results At breeding serum 25-OH D3 averaged 26.4 ng/ml (P = 0.20). Breeding 25-OH D3 was used as a covariate. Day 103 25-OH D3 was 47.0 and 40.4 ng/ml for ITM and MHAC:ITM respectively (P = 0.20). Weaning 25-OH D3 was 78.2 ng/ml for MHAC:ITM which tended (P < 0.10) to be greater than the 66.3 ng/ml in ITM serum. The d-103 to weaning rise in 25-OH D3 tended (P < 0.10) to be greater in MHAC:ITM (+16.5 ng/ml) than ITM (+4.5 ng/ml). Conclusion Supplementing 50 mcg/kg 25-OH D3 can increase vitamin D status within 1 parity. A MHAC:ITM blend fed throughout gestation and lactation tended to result in a greater weaning serum 25-OH D3.
维生素D对生长和发育至关重要,包括与骨骼相关的过程。繁殖母猪体内维生素D含量可能较低。维生素D受体是锌依赖受体。因此,可用的矿物质可能是优化维生素D状态所必需的。目的评价妊娠期和哺乳期饲喂矿源对母猪血清25-OH - D3浓度的影响。方法32头产母母猪(16组/组)分别饲喂100 ppm Zn、20 ppm Cu和40 ppm Mn,分别以羟基形式(ITM)或金属蛋氨酸羟基类似物双螯合物与ITM (MHAC:ITM)的50:50混合。在饲粮中添加50 mcg/kg 25-OH D3和1000 FTU/kg植酸酶。母猪以前没有接受过25-OH D3。在授精、妊娠d-103和产后21 d采集血清样本,分析25-OH D3浓度。结果血清25-OH D3平均为26.4 ng/ml (P = 0.20)。育种25-OH D3作为协变量。第103天,ITM和MHAC:ITM的25-OH D3分别为47.0和40.4 ng/ml (P = 0.20)。断奶25-OH D3在MHAC:ITM中为78.2 ng/ml,倾向于(P < 0.10)大于ITM血清中的66.3 ng/ml。25-OH D3在断奶前的d-103上升趋势(P < 0.10)在MHAC:ITM (+16.5 ng/ml)大于ITM (+4.5 ng/ml)。结论补充50 mcg/kg 25-OH D3可提高1胎内维生素D水平。妊娠期和哺乳期饲喂MHAC:ITM混合物的断奶血清中25-OH D3含量较高。
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引用次数: 0
50 Associations between maternal extreme heat exposure and inflammatory biomarkers in early and late pregnancy 妊娠早期和晚期产妇极端高温暴露与炎症生物标志物之间的关系
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.043
Evaniya Shakya, Sumera A Ali, Saleem Jessani, Cheyret Wood, Katerina Kechris, Yangyang Xu, Jennifer L Kemp, Jamie Westcott, Sarah Saleem, Blair J Wylie, Robert L Goldenberg, Nancy F Krebs, Kartik Shankar, Sarah Borengasser
: Introduction Maternal heat exposure has been linked to adverse pregnancy outcomes. The impact of high ambient temperature exposure on inflammation during human pregnancy remains largely unknown. Objective Determine the associations between preconception/ trimester-wise exposure to excessive heat stress (HS) and α1-acid glycoprotein (AGP) or C-Reactive Protein (CRP) at 12 and 34 weeks of gestation. Methods This secondary analysis included women with serum concentrations of AGP (n = 160), and CRP (n = 143) collected at 12 and 34 weeks of pregnancy from Women First Preconception Maternal Nutrition Trial in Thatta, Pakistan. Excessive HS was categorically defined as &gt; 20 days with average maximal daily temperature &gt;39 °C in each period: 90 days preconception (PreC), trimester 1 (T1), or trimester 2 (T2). Multiple linear regression was used to assess relationships between HS and each inflammatory marker in separate models for 12 and 34-weeks assessments, including adjustment for maternal characteristics, intervention arm, cluster, maternal anemia status, PM2.5 levels, and 12-week AGP or CRP (for 34-week outcomes). Results Exposure to HS during PreC increased 34-week AGP by 0.10 µg/mL compared to no HS exposure (p = 0.045). Exposure to HS compared to no exposure was positively associated with 34-week CRP (mg/L) during PreC (ß= 1.90, p = 0.015), T1 (ß= 2.06, p = 0.009), and T2 (ß= 1.93, p = 0.020). No significant associations were observed between exposure to HS and inflammatory markers at 12 weeks. Conclusion Findings suggest that preconception and early pregnancy HS may contribute to late-gestation inflammation.
孕妇热暴露与不良妊娠结局有关。在人类怀孕期间,高环境温度暴露对炎症的影响在很大程度上仍然未知。目的探讨孕前/孕期过度热应激(HS)与妊娠12周和34周α - 1-酸性糖蛋白(AGP)或c -反应蛋白(CRP)的关系。方法该二次分析纳入了来自巴基斯坦塔塔妇女第一孕前孕产妇营养试验的血清AGP浓度(n = 160)和CRP浓度(n = 143)的妇女,收集于妊娠12周和34周。过量HS被明确定义为&;gt;平均最高日气温20天;每个时期39°C:孕前90天(PreC),妊娠1 (T1)或妊娠2 (T2)。在12周和34周的评估中,使用多元线性回归评估HS与不同模型中每种炎症标志物之间的关系,包括调整产妇特征、干预组、集群、产妇贫血状况、PM2.5水平和12周AGP或CRP(34周结果)。结果与未暴露HS相比,PreC期间暴露HS使34周AGP升高0.10µg/mL (p = 0.045)。与未暴露相比,暴露于HS与PreC (ß= 1.90, p = 0.015)、T1 (ß= 2.06, p = 0.009)和T2 (ß= 1.93, p = 0.020)期间34周CRP (mg/L)呈正相关。12周时未观察到HS暴露与炎症标志物之间的显著关联。结论孕前和妊娠早期HS可能是妊娠后期炎症的重要因素。
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引用次数: 0
42 A polygenic risk score associated with gestational diabetes mellitus 42与妊娠期糖尿病相关的多基因风险评分
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.035
Karrah Peterson1,2, C Azure2, T Azure2, H Davis2, K Gourneau2, S LaRocque2, C Poitra2, S Poitra2, S Standish2, T J Parisien2, K J Morin2, Lyle G Best1,2
: Introduction Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy. GDM can increase risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, BMI, and family history have demonstrated strong association with GDM but no clear pathophysiology has been ascertained. Methods A diagnosis of GDM was abstracted from participant medical records. Analysis was conducted on 41 women with and 320 without GDM. Genotypes of 7 genetic variants were available. Additive and dominant genetic models were evaluated by chi-square and multivariate logistic regression methods. A genetic risk score comprised of total risk alleles among the 7 variants was also evaluated. Results Multivariate logistic regression showed significant, independent, positive associations between body-mass index (BMI), age, the posited genetic risk score and GDM. Genetic variant rs1421085 was associated with GDM in multivariate analysis (OR 2.12, 1.08-4.15, p = 0.029. The polygenic risk score showed association with GDM, odds ratio 1.27, 95% CI 1.09 - 1.48, p = 0.003. Discussion This relatively small cohort replicated a previously proposed polygenic risk score, as well as established risk factors for GDM (age and BMI). A previous meta-analysis in the literature reported a degree of heterogeneity between the 3 large cohorts analyzed, suggesting that the effect of these variants may differ according to genetic background. Conclusion We validate a previously published polygenic risk score for GDM in an ethically unrelated population. (Supported by NIGMS P20GM103442)
妊娠期糖尿病(Gestational diabetes, GDM)是一种发生在妊娠期的高血糖状态。GDM可增加分娩并发症的风险,以及随后母亲和后代发生2型糖尿病的风险。危险因素如饮食、身体质量指数和家族史已证实与GDM密切相关,但尚未确定明确的病理生理学。方法从患者病历中提取诊断为GDM的病例。对41名GDM患者和320名非GDM患者进行了分析。得到7个遗传变异的基因型。加性遗传模型和显性遗传模型采用卡方和多元逻辑回归方法进行评估。还评估了由7个变异中的总风险等位基因组成的遗传风险评分。结果多因素logistic回归显示,体重指数(BMI)、年龄、推定遗传风险评分与GDM之间存在显著、独立、正相关。多因素分析显示,rs1421085与GDM相关(OR 2.12, 1.08-4.15, p = 0.029)。多基因风险评分与GDM相关,比值比1.27,95% CI 1.09 ~ 1.48, p = 0.003。这个相对较小的队列重复了先前提出的多基因风险评分,以及GDM的既定风险因素(年龄和BMI)。先前文献中的一项荟萃分析报告了所分析的3个大型队列之间存在一定程度的异质性,表明这些变异的影响可能因遗传背景而异。结论:我们验证了先前发表的GDM多基因风险评分在非伦理人群中的有效性。(支持NIGMS P20GM103442)
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引用次数: 0
13 Trainee Award: Postnatal ω-3 polyunsaturated fatty acid supplementation partially resolves adiponectin receptor 2 deficits in skeletal muscle of IUGR-born lambs 13培训生奖:产后ω-3多不饱和脂肪酸补充部分解决iugr出生羔羊骨骼肌脂联素受体2缺陷
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.010
Shelley A Curry*, Melanie R White, Dustin T Yates
: Introduction Intrauterine growth restriction (IUGR) causes heightened inflammatory sensitivity in muscle that impairs insulin-stimulated metabolism. This may be facilitated by disruption of adiponectin signaling, which is an insulin sensitizer and is mutually antagonistic with inflammatory signaling. Objective This study evaluated the impact of supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (PUFA) on circulating adiponectin and muscle receptors in IUGR lambs. Methods Maternal heats stress was used to induce unsupplemented (n = 11) and ω-3 PUFA-supplemented (n = 12) IUGR lambs. Controls (n = 12) were born to pair-fed thermoneutral ewes. Blood was collected at 1 and 4 weeks of age to determine adiponectin (ELISA). Semitendinosus muscle was collected at necropsy (day 28) to quantify the adiponectin receptors, CDH13 and AdipoR2 (immunoblot). Results Semitendinosus CDH13 content did not differ among groups. AdipoR2 tended to be 63% less (P=0.09) for unsupplemented IUGR lambs than controls and was intermediate for ω-3 PUFA-supplemented IUGR lambs. Blood plasma adiponectin was 28% greater (P=0.04) for unsupplemented IUGR lambs (3.4±0.2 ng/mL) than for controls (2.7±0.1 ng/mL) and was intermediate for ω-3 PUFA-supplemented IUGR lambs (3.0±0.1 ng/mL), regardless of age. Conclusions These findings demonstrate a potential deficit in adiponectin signaling in IUGR neonatal muscle. Partial resolution of the deficit following ω-3 PUFA supplementation indicate that it was partially due to heightened inflammatory tone. The greater circulating adiponectin, which was also improved by ω-3 PUFA, was paradoxical but may have been a compensatory response to reduced adiponectin sensitivity. Nevertheless, these findings illustrate how anti-inflammatory intervention may improve muscle-centric IUGR metabolic outcomes. (Supported by USDA 2019-67015-29448, 2020-67015-30825)
当前位置宫内生长限制(IUGR)引起肌肉炎症敏感性增高,损害胰岛素刺激的代谢。脂联素是一种胰岛素增敏剂,与炎症信号相互拮抗。目的研究饲粮中添加抗炎ω-3多不饱和脂肪酸(PUFA)对IUGR羔羊循环脂联素和肌肉受体的影响。方法采用母体热应激诱导未添加ω-3 pufa的羔羊(n = 11)和添加ω-3 pufa的羔羊(n = 12)。对照组(n = 12)为成对饲养的热中性母羊。分别于1、4周龄采血测定脂联素(ELISA)。尸检(第28天)收集半腱肌,定量脂联素受体、CDH13和AdipoR2(免疫印迹)。结果半海参CDH13含量各组间无显著差异。未添加ω-3 pufa的IUGR羔羊的AdipoR2往往比对照组低63% (P=0.09), ω-3 pufa添加的IUGR羔羊的AdipoR2处于中间水平。无论年龄大小,未添加ω-3 pufa的IUGR羔羊血浆脂联素(3.4±0.2 ng/mL)比对照组(2.7±0.1 ng/mL)高28% (P=0.04), ω-3 pufa添加的IUGR羔羊血浆脂联素(3.0±0.1 ng/mL)处于中间水平。结论:这些发现表明IUGR新生儿肌肉中存在潜在的脂联素信号缺陷。ω-3 PUFA补充后赤字的部分解决表明,部分原因是炎症张力升高。ω-3 PUFA也改善了更大的循环脂联素,这是矛盾的,但可能是对降低脂联素敏感性的代偿反应。然而,这些发现说明了抗炎干预如何改善以肌肉为中心的IUGR代谢结果。(美国农业部资助2019-67015-29448,2020-67015-30825)
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引用次数: 0
27 Gestation stage and lactation impacts on nutrient retention in multiparous sows 妊娠期和哺乳期对多产母猪营养保留的影响
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.021
Bradley Lawrence, Jesus Acosta, Eric Myers, Chelsie Foran, Hans H Stein, Su A Lee, Andrea P Mallea, Deana Hancock
: Introduction Understanding nutrient retention during gestation and lactation is important for understanding sow nutrient demands. Little information is available regarding nutrient retention of multiparous sows during these phases. Objective Assess nutrient apparent total tract digestibility (ATTD) days 40 to 44 and 96 to 100 of gestation and mid-lactation. Methods During the gestation collection periods, sows were housed in individual metabolism crates. Total feces and urine was collected. Titanium dioxide (TiO2) was used as an indigestible marker in lactation. The study used 48 parity 2 through 6 sows. Gestation and lactation diets contained 1,000 FTU/kg of phytase and 50 mcg/kg of 25-OH D3. Results The ATTD of DM, N, GE, fat, total and insoluble fiber were not different (P &gt; 0.10) between stages of gestation but were lower in lactation than gestation (P &lt; 0.001). Ash, Ca and P ATTD were greater in later gestation than early gestation (P &lt; 0.001). Ash and Ca ATTD were lower in lactation than either stage of gestation (P &lt; 0.05) with P ATTD being similar in early gestation and lactation. The ATTD of K (P &lt; 0.05), Na and Mg (P &lt; 0.001) were lower in lactation than gestation. Gestation Zn, Cu, Mn and Fe ATTD were positive with no difference by stage of gestation (P &gt; 0.10). Lactation ATTD of Zn, Cu, Mn and Fe was negative and significantly lower than during either stage of gestation (P &lt; 0.01). Conclusion Late gestation appears to drive Ca and P retention while lactation appears to result in reduced Ca retention and net loss of Zn, Cu, Mn and Fe.
了解妊娠期和哺乳期的营养保留对了解母猪营养需求具有重要意义。在这些阶段,关于多产母猪营养保留的信息很少。目的评价妊娠40 ~ 44天和妊娠96 ~ 100天及泌乳中期营养物质表观全消化道消化率(ATTD)。方法在妊娠收集期间,将母猪饲养在个体代谢栏中。收集全部粪便和尿液。二氧化钛(TiO2)作为哺乳期不易消化的标志物。该研究使用了48头2至6胎母猪。妊娠期和哺乳期饲粮中添加1000 FTU/kg植酸酶和50 mcg/kg 25-OH D3。结果DM、N、GE、脂肪、总纤维和不溶性纤维的ATTD在妊娠期之间差异无统计学意义(P > 0.10),但哺乳期的ATTD低于妊娠期(P < 0.001)。Ash、Ca和P ATTD在妊娠后期高于妊娠早期(P < 0.001)。泌乳期灰分和钙的ATTD均低于妊娠期(P < 0.05), P ATTD在妊娠早期和泌乳期相似。哺乳期K (P < 0.05)、Na和Mg (P < 0.001)的ATTD均低于妊娠期。妊娠期Zn、Cu、Mn、Fe ATTD呈阳性,各妊娠期差异无统计学意义(P > 0.10)。哺乳期Zn、Cu、Mn和Fe的ATTD均为负,且显著低于妊娠期(P < 0.01)。结论妊娠后期促进钙、磷潴留,哺乳期降低钙潴留,锌、铜、锰、铁净流失。
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引用次数: 0
15 Impact of prematurity on the nutritional regulation of growth 15早产对生长营养调节的影响
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.012
Teresa A Davis*
Extrauterine growth restriction is common in premature infants and is largely attributed to reduced lean mass accretion. This reduced lean growth likely contributes to their increased lifelong risk for obesity and type 2 diabetes. There is critical need to identify mechanisms for the reduced growth and to develop targeted nutritional therapies to improve lean accretion. We showed in neonatal pigs born at term that post-meal surges in insulin and amino acids independently activate insulin and amino acid signaling pathways that stimulate mechanistic target of rapamycin complex 1 (mTORC1)-dependent translation initiation and protein synthesis in skeletal muscle. These anabolic actions promote more efficient use of amino acids for muscle protein synthesis and sustain rapid early postnatal growth rates. In contrast, preterm birth reduces relative weight gain and blunts the protein synthetic response in muscle to feeding. The reduced protein synthesis response in the preterm is due to reduced insulin- and amino acid-induced activation of mTORC1. This anabolic resistance to feeding likely contributes to the high prevalence of extrauterine growth restriction and reduced lean mass in prematurity. Supplementation with leucine, an essential amino acid and potent agonist of mTORC1, enhances translation initiation and protein synthesis in skeletal muscle and overall lean growth of neonatal pigs born at term. In the preterm, leucine supplementation also increases mTORC1 activity and protein synthesis, but higher doses are required. This suggests that the anabolic resistance of preterm muscle can be overcome by nutritional therapies targeted to stimulate mTORC1 signaling and protein synthesis and promote lean gain.
宫外生长受限在早产儿中很常见,主要是由于瘦质量增加减少。瘦肉生长的减少可能会增加他们一生中患肥胖症和2型糖尿病的风险。迫切需要确定生长减少的机制,并开发有针对性的营养疗法来改善瘦肉增加。我们在足月出生的新生猪中发现,餐后胰岛素和氨基酸的激增独立激活胰岛素和氨基酸信号通路,刺激骨骼肌中雷帕霉素复合物1 (mTORC1)依赖的翻译起始和蛋白质合成的机制靶标。这些合成代谢作用促进氨基酸更有效地用于肌肉蛋白质合成,并维持快速的出生后早期生长速度。相比之下,早产减少了相对的体重增加,并减弱了肌肉对喂养的蛋白质合成反应。早产儿中蛋白质合成反应的减少是由于胰岛素和氨基酸诱导的mTORC1激活减少。这种对喂养的合成代谢抵抗可能导致了早产儿宫外生长受限和瘦体重减少的高流行率。补充亮氨酸,一种必需氨基酸和mTORC1的强效激动剂,可以促进骨骼肌的翻译起始和蛋白质合成以及足月出生的新生猪的整体瘦肉生长。在早产儿,补充亮氨酸也会增加mTORC1活性和蛋白质合成,但需要更高的剂量。这表明,可以通过针对刺激mTORC1信号和蛋白质合成并促进瘦增重的营养疗法来克服早产儿肌肉的合成代谢抵抗。
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引用次数: 0
31 Trainee Award: Prenatal oxygen and glucose therapy rescues the immature β cell population and their transcriptomic signature in growth-restricted fetal sheep 31实习生奖:产前氧气和葡萄糖治疗可拯救生长受限胎羊的未成熟β细胞群及其转录组特征
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.025
Rosa I Luna-Ramirez*, Mariangel Varela, Miranda J Anderson, Sean W Limesand
: Introduction and objective Placental insufficiency (PI) reduces fetal oxygen and glucose concentrations, leading to fetal growth restriction (FGR), decreased β-cell mass, and reduced insulin production. Single-cell RNA sequencing (scRNA-seq) of fetal sheep islets identified different stages of β-cell maturation. FGR fetuses exhibited a higher mature-to-immature β-cell ratio compared to controls. We tested the hypothesis that supplemental oxygen and glucose to FGR fetus normalizes the immature β-cell population. Methods PI-FGR was induced by maternal hyperthermia. The oxygen and glucose therapy was delivered via maternal oxygen insufflation and fetal glucose infusion (FGR-OG, n = 5) for 7-10 days. FGR-AS received air and saline infusions (n = 5) and control fetuses were developed under thermoneutral conditions (n = 3). Pancreatic islet cells were isolated for scRNA-seq (10X Genomics). Differential gene expression (DESeq2, P &lt; 0.05) and pathway enrichment (KOBAS) were performed on the pseudo-bulked immature β-cell transcriptomes. Results FGR groups were growth restricted compared to controls (P &lt; 0.01). The immature-to-mature β-cell ratio was reduced in FGR-AS islets (1.7:1) compared to control (5.7:1) and FGR-OG (8.7:1) islets. Transcriptomic analysis of immature β-cells from FGR-AS fetus revealed upregulation of ribosome, oxidative phosphorylation, proteosome, metabolic ­pathways, spliceosome and RNA polymerase compared to control β-cells. In contrast, oxidative phosphorylation, spliceosome, ribosome, and proteosome were downregulated in FGR-OG compared to FGR-AS β-cells. No enriched pathways were detected between control and FGR-OG β-cells. Conclusion FGR accelerates β-cell maturation based on the augmentation of gene expression in metabolic pathways. Moreover, immature β-cells in FGR-OG fetuses preserve the immature β-cell pool because their transcriptomic profile was similar to immature β-cells from control fetuses, which together indicates the oxygen glucose therapy partially rescue dysregulated metabolic programming in pancreatic β-cells. (Supported by NIH R01-DK084842)
摘要:胎盘功能不全(PI)降低胎儿氧和葡萄糖浓度,导致胎儿生长受限(FGR), β细胞质量减少,胰岛素生成减少。胚胎羊胰岛的单细胞RNA测序(scRNA-seq)鉴定了β细胞成熟的不同阶段。与对照组相比,FGR胎儿表现出更高的成熟与未成熟β细胞比率。我们测试了补充氧气和葡萄糖给FGR胎儿使未成熟β细胞群正常化的假设。方法采用母体热疗诱导PI-FGR。氧糖治疗通过母体充氧加胎儿葡萄糖输注(FGR-OG, n = 5)进行,持续7-10天。FGR-AS组接受空气和生理盐水输注(n = 5),对照组在热中性条件下发育(n = 3)。分离胰岛细胞进行scRNA-seq (10X Genomics)检测。在伪膨大的未成熟β细胞转录组上进行差异基因表达(DESeq2, P < 0.05)和途径富集(KOBAS)。结果与对照组相比,FGR组生长受限(P < 0.01)。与对照组(5.7:1)和FGR-OG胰岛(8.7:1)相比,FGR-AS胰岛中未成熟到成熟的β细胞比例(1.7:1)降低。FGR-AS胎儿未成熟β-细胞转录组学分析显示,与对照β-细胞相比,核糖体、氧化磷酸化、蛋白体、代谢途径、剪接体和RNA聚合酶上调。与FGR-AS β-细胞相比,FGR-OG细胞的氧化磷酸化、剪接体、核糖体和蛋白体均下调。对照组和FGR-OG β-细胞之间未检测到富集通路。结论FGR通过增强β细胞代谢通路的基因表达来促进β细胞成熟。此外,FGR-OG胎儿的未成熟β-细胞保留了未成熟β-细胞库,因为它们的转录组学特征与对照胎儿的未成熟β-细胞相似,这共同表明氧糖治疗部分地挽救了胰腺β-细胞代谢程序失调。(NIH R01-DK084842资助)
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引用次数: 0
8 DHA and preterm birth: what we’ve learned since the 2018 Cochrane Review DHA和早产:自2018年Cochrane综述以来我们了解到的
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.006
Susan E Carlson, J Thomas Brenna
: Introduction A 2018 Cochrane Review concluded strong evidence that omega-3 fatty acids, including docosahexaenoic acid (DHA, 22:6n-3), prevented preterm birth (PB &lt; 37wks gestation) by 11% and early PB (EPB&lt;34wks gestation) by 42%, however, it did not determine dose or who was most likely to benefit from DHA supplementation. Objective The Assessment of DHA on Reducing Preterm Birth (ADORE) multicenter trial enrolled 1100 women between 12 and 20wks gestation and assigned them to 200 or 1000 mg/d DHA. Red blood cell phospholipid (RBC-PL) DHA and DHA intake (DHA-Food Frequency Questionnaire) were assessed at baseline. Results The higher dose reduced PB (PP = 0.95) and EPB (PP = 081). A secondary analysis found low DHA at baseline (&lt;6%total fatty acids) or low DHA intake (&lt;150mg/d) predicted who had reduced EPB (PP = 0.93) with 1000mg/d. Adherence to high dose (RBC-PL ≥8%) decreased PB by 58% (PP = 0.95) and EPB by 65% (PP = 0.94) in the low baseline DHA group. Black participants with high baseline DHA provided 1000mg had 6.4% PB and 2% EPB, below US rates. Our latest finding is that a FADS1 Insertion allele that increase arachidonic acid synthesis predicts women who benefit from high dose DHA supplementation; an allele found in 85.5% of Black and 48.6% of Other Races participating in ADORE. Conclusion Identification of the FADS I allele is a precision medicine strategy for primary prevention of PB and EPB. (Supported by NIH HD083292)
2018年Cochrane综述得出强有力的证据表明,包括二十二碳六烯酸(DHA, 22:6n-3)在内的omega-3脂肪酸可预防早产(妊娠37周)11%,预防早产早期(妊娠34周)42%,然而,它没有确定剂量或谁最有可能从DHA补充中受益。目的评价DHA对减少早产(ADORE)的作用,多中心试验纳入1100名妊娠12 ~ 20周的妇女,分别给予200或1000 mg/d DHA。基线时评估红细胞磷脂(RBC-PL) DHA和DHA摄入量(DHA-食物频率问卷)。结果高剂量小鼠血清PB (PP = 0.95)和EPB (PP = 081)均明显降低。第二次分析发现,基线低DHA(占总脂肪酸的6%)或低DHA摄入量(150mg/d)预测了1000mg/d的EPB降低(PP = 0.93)。在低基线DHA组中,坚持高剂量(RBC-PL≥8%)可使PB降低58% (PP = 0.95), EPB降低65% (PP = 0.94)。提供1000毫克高基线DHA的黑人参与者有6.4%的PB和2%的EPB,低于美国的水平。我们的最新发现是,增加花生四烯酸合成的FADS1插入等位基因预示着女性从高剂量DHA补充中受益;这个等位基因在85.5%的黑人和48.6%的其他种族中发现。结论FADS I等位基因的鉴定是预防PB和EPB的精准医学策略。(NIH HD083292支持)
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引用次数: 0
37 Palmitoleate protects against Zika virus infection-induced endoplasmic reticulum stress and apoptosis in neurons 棕榈油酸对寨卡病毒感染诱导的内质网应激和神经元凋亡具有保护作用
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.031
Chandan Krishnamoorthy, Anthony Delaney, Devanshi Shukla, Taija Hahka, Ann Anderson-Berry, Sathish Kumar Natarajan
Zika virus (ZIKV) infection during pregnancy is associated with the development of fetal complications such as microcephaly. We recently demonstrated that palmitoleate protects against ZIKV-induced apoptosis in placental trophoblasts. In the present study, we hypothesized that palmitoleate prevents ZIKV infection-induced endoplasmic reticulum (ER) stress and apoptosis in neurons. Neurons were infected with 0.1–1 multiplicity of infection of recombinant MR766 or PRVABC59 strains of ZIKV for an hour followed by treatment of palmitoleate (100–200 µM) for different post-infection time points. Apoptosis was measured by nuclear morphological changes, caspase 3/7 activity, and immunoblot analysis of pro-apoptotic mediators. Activation of ER stress markers and viral envelope levels were detected using RT-qPCR and immunoblot. Infectious virus particles were measured by using plaque assay. ZIKV infection to neuronal cells showed increased pro-apoptotic markers like cleaved-PARP, cleaved caspase-3, Bim, and Puma, whereas decreased levels of anti-apoptotic markers such as Mcl-1, Bcl-1, and Bcl-xL. Further, we observed activation of three arms of ER stress: inositol requiring enzyme 1 alpha (IRE1), protein kinase-like ER kinase (PERK), and activating transcription factor (ATF6) pathways with ZIKV infection. Treatment of palmitoleate dramatically decreased ZIKV infection-induced increase in percent apoptotic nuclei and caspase 3/7 activity. Further, treatment of palmitoleate decreased cleaved PARP and PUMA protein expressions. Treatment of palmitoleate reduced ZIKV-induced ER stress activation as evidenced by decreased levels of phosphorylated forms of IRE1 and eukaryotic initiation factor 2 alpha; decreased expressions of cleaved ATF6, spliced X-box associated protein 1 and C/EBP homologous protein compared to ZIKV infection alone. Further, treatment of palmitoleate attenuated ZIKV envelope levels and infectious titer in SH-SY5Y and primary fetal cortical neurons isolated from humanized STAT2 knockin mice. These data suggest that palmitoleate supplementation protects against ZIKV-induced neuronal ER stress, apoptosis and decreases Zika viral load thereby mitigates neuronal damage.
妊娠期寨卡病毒感染与胎儿并发症(如小头畸形)的发生有关。我们最近证明棕榈油酸酯可以防止寨卡病毒诱导的胎盘滋养细胞凋亡。在本研究中,我们假设棕榈油酸酯可以预防寨卡病毒感染诱导的内质网应激和神经元凋亡。用0.1-1倍感染重组MR766或PRVABC59的ZIKV菌株感染神经元1小时,然后在不同感染后时间点用棕榈油酸酯(100-200µM)处理。通过核形态变化、caspase 3/7活性和促凋亡介质的免疫印迹分析来检测细胞凋亡。采用RT-qPCR和免疫印迹法检测内质网应激标志物的激活和病毒包膜水平。采用空斑法测定传染性病毒颗粒。寨卡病毒感染神经元细胞后,其促凋亡标志物如cleaved- parp、cleaved caspase-3、Bim和Puma增加,而抗凋亡标志物如Mcl-1、Bcl-1和Bcl-xL水平降低。此外,我们观察到内质网应激的三个分支:肌醇需要酶1 α (IRE1)、蛋白激酶样内质网激酶(PERK)和激活转录因子(ATF6)途径在寨卡病毒感染时被激活。棕榈油酸处理显著降低了ZIKV感染诱导的凋亡细胞核百分比和caspase 3/7活性的增加。此外,棕榈油酸处理降低了裂解PARP和PUMA蛋白的表达。棕榈油酸处理降低了zikv诱导的内质网应激激活,IRE1和真核起始因子2 α磷酸化形式的水平降低证明了这一点;与单独感染ZIKV相比,断裂的ATF6、剪接的X-box相关蛋白1和C/EBP同源蛋白的表达降低。此外,棕榈油酸降低了从人源化STAT2敲入蛋白小鼠分离的SH-SY5Y和原代胎儿皮质神经元的ZIKV包膜水平和感染滴度。这些数据表明,补充棕榈油酸酯可以防止寨卡病毒诱导的神经元内质网应激和细胞凋亡,并减少寨卡病毒载量,从而减轻神经元损伤。
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引用次数: 0
14 Effects of vitamin and mineral supplementation fed to F0 beef heifers throughout pregnancy on hepatic gene expression of the F2 generation 妊娠期补饲维生素和矿物质对F0肉牛F2代肝脏基因表达的影响
IF 3.3 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2025-12-19 DOI: 10.1093/jas/skaf398.011
Roberta B A Dahlen, Wellison J S Diniz, Jennifer L Hurlbert, Ana Clara B Menezes, Kendall C Swanson, Carl R Dahlen
Supplementing pregnant F0 beef heifers with vitamins and minerals throughout pregnancy has been shown to alter development of F1 offspring, but questions of whether outcomes persist across generations remain. In this study, F0 dams were managed on one of two dietary treatments throughout pregnancy: 1) basal diet (CON, n = 7), or 2) basal diet with vitamin and mineral supplement (VTM, n = 8). At parturition, F1 heifers were managed as a single group throughout the experiment. All F1 heifers were bred via artificial insemination using female-sexed semen from a single sire and confirmed pregnant with female calf. At d 250 of gestation, F1 dams were harvested for collection of F2 fetal liver samples. Liver tissues from F2 fetuses underwent total RNA isolation and sequencing. After data quality control, reads were mapped using the STAR aligner and final statistical analyses were conducted with R (v4.4.2). Through differential expression analysis with DESeq2, we identified 269 differentially expressed genes (P- value ≤ 0.05 and |log2FC| ≥ 0.5). The most prevalent affected genes included SHH, EDN1, LEF1, SFRP1, ESR1, AR, and BMP7, which are involved in key biological pathways related to hepatic function – including energy metabolism, lipid biosynthesis, and liver health; as well as muscle function – particularly satellite cell proliferation critical for postnatal muscle growth and skeletal tissue regeneration. These findings suggest that providing vitamin and mineral supplementation to F0 dams during pregnancy induces effects on the F2 generation, including greater expression of genes that may enhance hepatocyte development and myocyte proliferation. (Supported by the USDA 2022-67016-36479).
在怀孕期间为怀孕的F0肉牛补充维生素和矿物质已被证明可以改变F1后代的发育,但这种结果是否会在几代之间持续存在的问题仍然存在。在本研究中,F0只母鼠在妊娠期间采用两种饮食处理之一:1)基础日粮(CON, n = 7),或2)基础日粮中添加维生素和矿物质(VTM, n = 8)。在分娩时,F1小母牛在整个试验期间作为一组进行管理。所有F1小母牛都是通过人工授精,使用来自单一父系的雌性精液,并确认怀孕了雌性小牛。在妊娠第250天,采集F1胎鼠,采集F2胎肝样本。对F2胎肝组织进行总RNA的分离和测序。在数据质量控制后,使用STAR校准器绘制reads图谱,最后使用R (v4.4.2)进行统计分析。通过DESeq2的差异表达分析,我们鉴定出269个差异表达基因(P值≤0.05,|log2FC|≥0.5)。最常见的受影响基因包括SHH、EDN1、LEF1、SFRP1、ESR1、AR和BMP7,它们参与与肝功能相关的关键生物学途径,包括能量代谢、脂质生物合成和肝脏健康;以及肌肉功能,特别是卫星细胞的增殖,对产后肌肉生长和骨骼组织再生至关重要。这些发现表明,在怀孕期间向F0水坝补充维生素和矿物质会对F2代产生影响,包括可能促进肝细胞发育和肌细胞增殖的基因的更大表达。(美国农业部支持,2022-67016-36479)。
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Journal of animal science
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