Domestic animal endocrinology最新文献_第2页

Active immunization with a novel recombinant GnRH vaccine inhibits reproductive function in male goats 一种新型重组GnRH疫苗的主动免疫抑制公山羊的生殖功能。

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-12-15 DOI: 10.1016/j.domaniend.2024.106908

Moyan Di , Xinbao Gong , Yanyun Zhu , Shibao Guo , Zhihao Pan , Mengxian Li , Zhuoya Wu , Wei Zhang , Xuelan Liu , Ya Liu , Yunsheng Li , Jian Li , Fugui Fang

Gonadotropin-releasing hormone (GnRH) vaccines have been widely used to effectively inhibit gonadal development and reproductive function. To improve the immunogenicity of GnRH, we developed and evaluated the effects of GnRH6-kisspeptin-CRM197 immunization on the reproductive function in male goats. Thirty 3-month-old male goats (n = 30) were randomly assigned to control, surgical, and immunized groups. The immunized group received a 2 mL injection of the GnRH6-kisspeptin-CRM197 with a booster administered four weeks later. The control group was administered a white oil adjuvant. Blood samples were collected at regular intervals, and at week 20, the animals were euthanized for tissue collection. Serum antibody titers and testosterone levels were measured using ELISA and CLIA, respectively. Testicular parameters and histology were evaluated. The mRNA levels of reproductive-related genes in the HPG axis were measured using RT-qPCR. The results showed that the immunized goats had significantly increased serum GnRH and kisspeptin antibodies (P < 0.05) but decreased testosterone concentrations (P < 0.05) compared to the control group. Testicular size and histology were significantly affected in the immunized group, with notable reductions in testicular weight and dimensions (P < 0.01), and evidence of vacuolar degeneration and suppressed sperm production. The mRNA levels of FSHβ and LHβ in the pituitary, as well as FSHR, LHR, 3βHSD, and 17βHSD in the testis, were significantly lower in the immunized group compared to controls (P < 0.05). These findings suggest that GnRH6-kisspeptin-CRM197 is a safe antigen and a promising immunocastration vaccine with enhanced efficacy.

促性腺激素释放激素（GnRH）疫苗被广泛用于有效抑制性腺发育和生殖功能。为了提高GnRH的免疫原性，我们研制并评价了GnRH6-kisspeptin-CRM197免疫对公山羊生殖功能的影响。30只3月龄公山羊（n = 30）随机分为对照组、手术组和免疫组。免疫组接受2ml GnRH6-kisspeptin-CRM197注射，四周后给予加强剂。对照组给予白油佐剂。定期收集血液样本，在第20周，对动物实施安乐死以收集组织。血清抗体滴度和睾酮水平分别采用ELISA和CLIA测定。评估睾丸参数和组织学。RT-qPCR检测HPG轴生殖相关基因mRNA表达水平。结果表明：与对照组相比，免疫组山羊血清GnRH和kisspeptin抗体显著升高（P < 0.05），睾酮浓度显著降低（P < 0.05）；免疫组大鼠睾丸大小和组织学均受到显著影响，睾丸重量和尺寸均显著降低（P < 0.01），且有空泡变性和精子产生抑制的证据。免疫组大鼠垂体FSHβ、LHβ mRNA表达水平以及睾丸FSHR、LHR、3βHSD、17βHSD mRNA表达水平均显著低于对照组（P < 0.05）。这些结果表明GnRH6-kisspeptin-CRM197是一种安全的抗原，也是一种有前景的免疫去势疫苗。

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引用次数: 0

17β-estradiol inhibits lipopolysaccharide-induced inflammation and pyroptosis of Leydig cells of the domestic yak (Bos grunniens) via the SIRT1/Nox4/ROS pathway 17β-雌二醇通过SIRT1/Nox4/ROS通路抑制脂多糖诱导的家牦牛间质细胞炎症和焦亡。

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-12-10 DOI: 10.1016/j.domaniend.2024.106906

Junyuan Ma , Yanmei Yang , Lin He , Chongfa Yang , Yahua Yang , Yang Li , Wen He , Xiaoying Niu , Zhou Chen , Songming Hu , Jin'e Wang , Yingpai Zhaxi , Shengdong Huo

Estradiol (E2) secreted by Leydig cells (LCs) can accumulate in the testes due to constriction of the reproductive lumen. Estrogen is not only important for reproduction, but also protects against inflammation. In this study, the role of pyroptosis in testicular inflammation and the effects of E2 against inflammation and pyroptosis of yak interstitial cells were investigated. Inflamed testes exhibited structural damage and pyroptosis with decreased E2, testosterone, and estrogen receptor β (ERβ) levels in testicular fluid. E2 alone inhibited testosterone secretion and increased ERβ expression in mature LCs. In LCs, lipopolysaccharide (LPS) causes inflammation by activation of TNF-α and IL-6, and pyroptosis via activation of the classical and non-classical pyroptosis pathways. LPS inhibits sex hormone secretion and ERβ expression in LCs. E2 inhibited the LPS-induced decrease of ER expression in LCs and also inhibited LPS-induced interstitial cell inflammation and pyroptosis, which was partially blocked by Selisistat (EX-527, SIRT1 inhibitor) or Fulvestrant (ICI 182,780, E2 non-genomic receptor inhibitors). In conclusion, E2 relieved LPS-induced inflammation and pyroptosis of yak LCs via the SIRT1/Nox4/ROS pathway. This finding provides new insights into the role of estrogen in male reproductive health and offers a potential therapeutic strategy to improve testicular immune and reproductive function by modulating hormonal homeostasis.

雌二醇（E2）由莱狄格细胞（LC）分泌，会因生殖腔收缩而积聚在睾丸中。雌激素不仅对生殖很重要，还能防止炎症。本研究调查了牦牛睾丸间质细胞炎症中的热凋亡作用以及E2对炎症和热凋亡的影响。发炎的睾丸表现出结构性损伤和热解，睾丸液中的E2、睾酮和雌激素受体β（ERβ）水平下降。单用 E2 可抑制睾酮分泌，并增加成熟睾丸细胞中 ERβ 的表达。在 LCs 中，脂多糖（LPS）通过激活 TNF-α 和 IL-6 引起炎症，并通过激活经典和非经典的热解途径引起热解。LPS 可抑制 LCs 中性激素的分泌和 ERβ 的表达。E2可抑制LPS诱导的LCs中ER表达的减少，还可抑制LPS诱导的间质细胞炎症和裂解，Selisistat（EX-527，SIRT1抑制剂）或Fulvestrant（ICI 182,780，E2非基因组受体抑制剂）可部分阻断LPS诱导的间质细胞炎症和裂解。总之，E2通过SIRT1/Nox4/ROS途径缓解了LPS诱导的牦牛LCs炎症和脓毒症。这一发现为了解雌激素在男性生殖健康中的作用提供了新的视角，并为通过调节激素平衡改善睾丸免疫和生殖功能提供了一种潜在的治疗策略。

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引用次数: 0

Poor maternal nutrition during gestation in sheep alters key hormonal systems involved in energy homeostasis and appetite in the offspring 绵羊妊娠期间母体营养不良会改变与后代能量平衡和食欲有关的关键激素系统。

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-12-10 DOI: 10.1016/j.domaniend.2024.106907

Nicole M. Tillquist, Kristen E. Govoni, Steven A. Zinn, Sarah A. Reed

Disturbances in maternal nutrient availability through increased or decreased abundance of specific or total nutrients during pre-natal development can have negative impacts on offspring growth. These changes are likely mediated, at least in part, by hormonal systems that control energy homeostasis and appetite. Regulation of insulin signaling is critical to ensuring appropriate glucose homeostasis. Poor maternal nutrition during gestation impacts circulating glucose and insulin concentration in both the dam and offspring, reducing circulating insulin and glucose in offspring of restricted-fed dams and increased circulating insulin and glucose in the offspring of over-fed dams. Leptin and ghrelin are key regulators of appetite and feed intake. Offspring of over-fed ewes often exhibit leptin resistance, which may lead to changes in adiposity. Leptin responses in offspring of restricted-fed ewes are not well defined, although restricted-fed ewes themselves exhibit decreased circulating leptin concentrations. Little is known about the effects of poor maternal nutrition on offspring ghrelin. Glucocorticoids and thyroid hormones are required for appropriate fetal development. Poor maternal nutrition during gestation alters the development of the hypothalamic-pituitary-adrenal and thyroid axes in the offspring, although the effects vary according to the type, duration, timing, and severity of the nutritional insult. The relationships between insulin, leptin, ghrelin, glucocorticoids, and thyroid hormones can result in synergistic effects, exacerbating negative outcomes for the offspring. The impacts of poor maternal nutrition are multi-faceted, and the resulting alterations in body composition can continue to impact hormone regulation beyond the initial insult caused by poor maternal nutrition during gestation.

在产前发育期间，通过增加或减少特定或总营养素丰度而引起的母体营养可利用性紊乱可对后代生长产生负面影响。这些变化可能是由控制能量平衡和食欲的荷尔蒙系统介导的，至少部分是这样。胰岛素信号的调节是确保适当的葡萄糖稳态的关键。妊娠期母体营养不良会影响母鼠和子代的循环胰岛素和胰岛素浓度，限制喂养母鼠子代的循环胰岛素和葡萄糖浓度降低，过量喂养母鼠子代的循环胰岛素和葡萄糖浓度升高。瘦素和胃饥饿素是食欲和采食量的关键调节因子。过度喂养母羊的后代经常表现出瘦素抵抗，这可能导致肥胖的变化。限制喂养母羊的后代瘦素反应尚不清楚，尽管限制喂养母羊本身表现出循环瘦素浓度降低。关于母体营养不良对后代生长素的影响，人们知之甚少。糖皮质激素和甲状腺激素是胎儿正常发育所必需的。妊娠期母亲营养不良会改变后代下丘脑-垂体-肾上腺和甲状腺轴的发育，尽管其影响因营养不良的类型、持续时间、时间和严重程度而异。胰岛素、瘦素、胃饥饿素、糖皮质激素和甲状腺激素之间的关系可能导致协同效应，加剧对后代的负面影响。母亲营养不良的影响是多方面的，由此导致的身体成分的改变可以继续影响激素调节，而不仅仅是怀孕期间母亲营养不良造成的最初损害。

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引用次数: 0

Evaluation of serum insulin-like growth factor 1 concentrations in non-diabetic cats with chronic kidney disease 慢性肾病非糖尿病猫血清胰岛素样生长因子1浓度的评价

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-11-28 DOI: 10.1016/j.domaniend.2024.106898

J.P. Rey Amunategui , E.M. Molina , G.A. Pompili , J. Mas , O.P. Pignataro , D.D. Miceli

Feline hypersomatotropism (HST) can develop in both diabetic and non-diabetic cats, but studies evaluating the prevalence of HST in cats without diabetes mellitus (DM) are lacking. The aims of the study were to evaluate circulating insulin-like growth factor 1 (IGF-1) in non-diabetic cats with chronic kidney disease (CKD), to assess whether there is a correlation between general test of renal function and IGF-1 concentration in cats with CKD, and to screen this population for the presence of HST. In this prospective study, one hundred fifty-four non-diabetic cats (n = 154) with CKD from referral centers in Buenos Aires (Argentina) were evaluated. Serum IGF-1 concentration was measured as part of the routine tests for CKD and compared with a healthy control group of 50 cats without CKD. The median serum IGF-1 concentration in the total population of cats with CKD was 500 ng/mL (range 34–1593 ng/mL). Median serum IGF-1 concentrations of cats with IRIS stage 1 (n = 13), stage 2 (n = 86), stage 3 (n = 40) and stage 4 (n = 15) of CKD were 230 ng/mL (range 58–951 ng/mL), 473 ng/mL (range 34–1456 ng/mL), 597 ng/mL (range 123–1593 ng/mL), 569 ng/mL (range 123–1045 ng/mL), respectively. None of the cats in the control group had IGF-1 concentration >1000 ng/mL (median 505 ng/mL, range 114–720 ng/mL). There was a positive linear correlation between serum IGF-1 and creatinine concentrations in cats with CKD (r= 0.22, 95% confidence interval 0.06–0.37 P=0.005). A proportion of 5.8% (95% confidence interval 2.7-10.8%) of non-diabetic cats with CKD had markedly increased IGF-1 concentrations (cut-off IGF-1 >1000 ng/mL). Pituitary enlargement was detected on computed tomography in 3/4 of these cases. Eighteen cats (11.6%) had serum IGF-1 concentrations in the “grey zone” between 800 and 1000 ng/mL. A small proportion of non-diabetic cats with CKD had an IGF-1 concentration in a range that is consistent with HST in diabetic cats. Likewise, the progression of CKD in cats without DM correlates with increases in serum IGF-1 concentrations.

猫促生长机能亢进（HST）可发生在糖尿病猫和非糖尿病猫身上，但缺乏评估非糖尿病猫HST患病率的研究。本研究的目的是评估患有慢性肾脏疾病（CKD）的非糖尿病猫的循环胰岛素样生长因子1 (IGF-1)，评估CKD猫的一般肾功能测试与IGF-1浓度之间是否存在相关性，并筛查该人群是否存在HST。在这项前瞻性研究中，来自布宜诺斯艾利斯（阿根廷）转诊中心的154只患有CKD的非糖尿病猫（n = 154）被评估。血清IGF-1浓度作为CKD常规测试的一部分进行测量，并与50只无CKD的健康对照组进行比较。CKD猫的中位血清IGF-1浓度为500 ng/mL（范围34-1593 ng/mL）。IRIS CKD 1期（n = 13）、2期（n = 86）、3期（n = 40）和4期（n = 15）猫的血清IGF-1浓度中值分别为230 ng/mL（范围58-951 ng/mL）、473 ng/mL（范围34-1456 ng/mL）、597 ng/mL（范围123-1593 ng/mL）、569 ng/mL（范围123-1045 ng/mL）。对照组中没有猫的IGF-1浓度为1000 ng/mL（中位数505 ng/mL，范围114-720 ng/mL）。CKD猫血清IGF-1与肌酐浓度呈线性正相关（r= 0.22, 95%可信区间为0.06-0.37 P=0.005）。5.8%（95%置信区间为2.7-10.8%）的非糖尿病猫CKD的IGF-1浓度显著升高（截止IGF-1浓度为1000 ng/mL）。其中3/4的病例在计算机断层扫描上发现垂体肿大。18只猫（11.6%）的血清IGF-1浓度在800至1000 ng/mL之间的“灰色地带”。一小部分患有CKD的非糖尿病猫的IGF-1浓度范围与糖尿病猫的HST一致。同样，没有糖尿病的猫的CKD进展与血清IGF-1浓度的增加相关。

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引用次数: 0

Correlation of Anti-Müllerian hormone serum concentration measured in proestrus and estrus with the litter size as a fertility marker in bitches 母狗发情前期和发情期血清抗<s:1>勒氏激素浓度与产仔数的相关性研究。

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-11-28 DOI: 10.1016/j.domaniend.2024.106897

Theresa Hornberger , Sven Reese , Klaus Perbandt , Andrea Meyer-Lindenberg , Beate Walter

The use of the anti-Müllerian hormone (AMH) serum concentration as a fertility marker has been shown in cows, sheep and mares and has been indicated in one study in female dogs. The aim of this study was to investigate the connection between the AMH serum concentration, taken at two defined time points during the bitch`s heat, and the litter size to investigate whether AMH can be used as a practical measurement for the individual breeding bitch to predict litter size. The study was carried out on 27 healthy female dogs presented for pre-breeding examination, considering all previously known influencing factors on AMH in the bitch such as age, body weight and estrous cycle phase at the time the sample was taken. Due to the AMH increase in early proestrus and its drop around ovulation, AMH was measured in blood samples taken within the first three days of heat (AMH1) and near ovulation (AMH2) with AMH1 being significantly higher than AMH 2 (p < 0.001). There was a highly significant negative correlation of body weight and AMH at both sampling times (p < 0.001). There were no significant results when the dogs were paired and grouped according to high or low AMH concentrations, but a significant effect of AMH serum concentration on litter size was found in the multifactorial analysis when the dogs were matched according to their body weight (AMH1: p = 0.022; AMH2: p = 0.030). In conclusion, a significant effect of the AMH concentration and the litter size among female dogs with matching body weight could be found, but a much larger sample collection is needed to evaluate reference intervals for AMH for bitches of different weight to predict the fertility of an individual bitch in the future.

抗勒氏杆菌激素（AMH）血清浓度已在牛、羊和母马身上得到证实，并在一项对母狗的研究中得到证实。由于AMH在发情前期升高，而在排卵期前后下降，因此在发情期前3天（AMH1）和排卵期前3天（AMH2）血样中测定AMH， AMH1明显高于AMH2 （p < 0.001）。在两个采样时间，体重与AMH呈极显著负相关（p < 0.001）。按AMH浓度高低配对分组时，多因素分析无显著结果，但按体重配对时，血清AMH浓度对产仔数有显著影响(AMH1: p = 0.022；AMH2: p = 0.030)。

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引用次数: 0

The structure of the porcine uterine-conceptus interface is associated with gestational day, fetal size and sex 猪子宫-胎盘界面的结构与妊娠日、胎儿大小和性别有关

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-11-20 DOI: 10.1016/j.domaniend.2024.106895

Tailine Rayane Lima Reis , João Vitor Lopes-Ferreira , Karen Beatriz Guerra , Luana Alice Boggione da Silva , Claire Stenhouse , Cheryl Joy Ashworth , Enrrico Bloise , Hélio Chiarini-Garcia , Fernanda Radicchi Campos Lobato de Almeida

This study aimed to characterize histological changes of the maternal-conceptus interface in feto-placental units associated with fetal weight and sex throughout pregnancy. Pregnant Large-White X Landrace gilts(n=18) were euthanized and hysterectomized on gestational days[GDs] 30(n=3), 45(n=5), 60(n=5), and 90(n=5). Intact cross-sections of fetoplacental interface associated with the lightest[LW] and normally-grown[NW] littermates were collected on GD30(n=4 per size). On GDs 45, 60 and 90, interactions between fetal size and sex were investigated in light-weight males[LWM] and females[LWF]; normal-weight males[NWM] and females[NWF] (n=4/group/GD). Fetal weight did not affect the endometrium composition, including relative proportion of glandular epithelium, blood vessels, and connective tissue. Feto-placental units from LW embryos tended to have longer chorioallantoic fold length on GD30(P=0.06). On GD45, higher proportion of larger endometrial glands was observed in NWM, and taller trophoblastic epithelium in NW conceptuses, regardless of sex(P<0.05). NWF presented the greatest proportion of subluminal endometrial epithelial blood vessels(P<0.05). On GD60, more blood vessels were present at the folds’ base in males feto-placental units, whereas taller trophoblastic epithelium were present in NWF fetuses’ feto-placental units(P<0.05). Feto-placental units’ morphological composition throughout gestation in NW and LW conceptuses revealed that fold length was higher as early as GD30, with no further increase up to GD90 in LW conceptuses(P>0.05). Increased proportion of glandular epithelium was observed in LW conceptuses; the highest percentage present on GD90(P<0.05). Collectively, we demonstrated that fetal weight and sex influence the morphological structure of feto-placental units from as early as GD30, suggesting potential differences in the ability for nutrient transport.

本研究旨在描述胎儿-胎盘单位中母体-胎盘界面的组织学变化与整个孕期胎儿体重和性别的关系。怀孕的大白X兰德良种后备母猪（18头）在妊娠天数[GDs] 30（3头）、45（5头）、60（5头）和90（5头）时被安乐死并切除子宫。在妊娠日 30（n=4）收集最轻[LW]胎仔和正常生长[NW]胎仔的胎盘界面完整横截面。在发育期45、60和90，研究了胎儿体重轻的雄性[LWM]和雌性[LWF]、体重正常的雄性[NWM]和雌性[NWF]（n=4/组/发育期）的胎儿大小与性别之间的相互作用。胎儿体重不影响子宫内膜的组成，包括腺上皮、血管和结缔组织的相对比例。在 GD30，LW 胚胎的胎盘单位往往具有较长的绒毛膜褶皱长度（P=0.06）。在 GD45 时，无论性别如何，NWM 中较大的子宫内膜腺体比例较高，NW 胎儿的滋养层上皮较高（P<0.05）。北西胎膜下子宫内膜上皮血管的比例最大（P<0.05）。在 GD60，雄性胎盘单位褶皱底部的血管较多，而在雌性胎盘单位中滋养上皮较高（P<0.05）。NW和LW受孕胎儿胎盘单位在整个妊娠期的形态组成显示，LW受孕胎儿胎盘单位的折叠长度早在妊娠期30天时就较高，到妊娠期90天时不再增加（P>0.05）。在长绒棉受孕胎儿中观察到腺上皮比例增加；在广东十一选五90天时比例最高（P<0.05）。总之，我们证明胎儿体重和性别早在GD30时就会影响胎儿-胎盘单位的形态结构，这表明胎儿的营养运输能力可能存在差异。

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引用次数: 0

Distribution and sequence analysis of the melanocortin 2 receptor in horses and ponies 马和小马体内黑色素皮质素 2 受体的分布和序列分析

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-11-20 DOI: 10.1016/j.domaniend.2024.106896

Christina M. Cash, Melody A. de Laat

The melanocortin 2 receptor (MC2R) has relevance to equine pituitary pars intermedia dysfunction (PPID), as it is the primary binding site for ACTH, which circulates at elevated concentrations in animals affected by PPID. Despite this, little is known about MC2R in equine species. The overall aim of this investigation was to determine MC2R mRNA expression in tissues relevant to PPID in healthy horses and to examine the MC2R gene sequence in a cohort of horses and ponies with and without PPID. The study found that the MC2R gene was expressed in both adrenal and pituitary gland tissues as reported in other mammalian species. However, no expression was seen in adipose or skin tissue. An investigation of the tissue distribution and functionality of the MC2R in individuals with PPID is now recommended. Then, we investigated the coding regions (exons) of the equine MC2R gene for variations associated with PPID in a limited number of animals. This was performed using a hybridised gene capture and next generation sequencing method which found a 100% pairwise identity between all 28 individuals in the study, and with the reference genome sequence. This preliminary study found no evidence of major genetic variations in the coding region of the MC2R gene associated with PPID, though variants affecting expression may occur in the introns or remain unidentified within the exons of the gene and studies on a larger scale are required.

黑皮质素 2 受体（MC2R）与马垂体中叶旁腺功能障碍（PPID）有关，因为它是促肾上腺皮质激素（ACTH）的主要结合位点，在受 PPID 影响的动物体内，ACTH 的循环浓度会升高。尽管如此，人们对马的 MC2R 却知之甚少。这项调查的总体目标是确定健康马匹与 PPID 相关的组织中 MC2R mRNA 的表达情况，并研究患有和未患有 PPID 的马匹和小马的 MC2R 基因序列。研究发现，MC2R 基因在肾上腺和垂体组织中均有表达，这在其他哺乳动物中也有报道。但是，在脂肪或皮肤组织中没有发现表达。因此，我们建议对 MC2R 在 PPID 患者体内的组织分布和功能进行调查。随后，我们对马 MC2R 基因的编码区（外显子）进行了调查，以确定在有限数量的动物中是否存在与 PPID 相关的变异。这项研究采用杂交基因捕获和下一代测序方法进行，发现研究中的所有 28 个个体与参考基因组序列之间的配对一致性达到 100%。这项初步研究没有发现与 PPID 相关的 MC2R 基因编码区存在重大遗传变异的证据，但影响表达的变异可能发生在基因内含子中，或在基因外显子中仍未被发现，因此需要进行更大规模的研究。

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引用次数: 0

Short-term clinical and biochemical responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia: A retrospective case series 高胰岛素血症马匹接受达帕格列净或ertugliflozin治疗后的短期临床和生化反应：回顾性病例系列

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-11-19 DOI: 10.1016/j.domaniend.2024.106894

Tania Sundra , Edd Knowles , David Rendle , Erin Kelty , Guy Lester , Gabriele Rossi

The metabolic and lipid profiles of horses treated with sodium-glucose cotransporter 2 inhibitors are not well understood. This retrospective study evaluated blood parameters in hyperinsulinemic horses treated with either ertugliflozin (0.05 mg/kg) or dapagliflozin (0.02 mg/kg) orally once daily. Blood samples were collected at baseline (day 0) and after 7 and/or 30 days of treatment. Statistical analyses were conducted using Wilcoxon signed-rank, Mann-Whitney and Spearman's rank correlation tests. Thirty-four horses received dapagliflozin and 24 received ertugliflozin. Significant (p<0.05) within-horse changes between day 0 and day 30 included [median, inter-quartile range (IQR)]: basal serum [Insulin] (uU/ml) reduced 170 (92-280) to 28.7 (14.5-90); [triglycerides] (mmol/l) increased 0.5 (0.3-0.6) to 1.0 (0.6-1.56), [β-hydroxybutyrate] (umol/l) increased 0.22 (0.17-2.7) to 0.30 (0.24-0.35); [total cholesterol] (mmol/l) increased 2.36 (2-2.6) to 2.84 (2.4-3.7); and GGT (IU/ml) increased 21 (16-32) to 25 (18-38). As a percentage of total serum lipids, high-density lipoprotein (HDL) reduced 52.4 % (47.9 %-61.0 %) to 50 % (41 %-54.8 %) and very-low density lipoprotein (VLDL) increased 10.4 % (6.4 %-14.4 %) to 12.3 % (9.9 %-16.8 %) (all p<0.05). Differences between ertugliflozin and dapagliflozin groups were not significant in any of these parameters at days 0, 7 or 30. At day 30, 10/48 (21 %) cases had [triglycerides] > 2.0 mmol/l (maximum = 10.8mmol/l). Day 30 [triglyceride] correlated with day 0: basal insulin (rho=0.47); [triglyceride] (rho=0.42); %VLDL (rho=0.34) day 30: [total cholesterol] (rho=0.67), %HDL (rho=-0.432) and %VLDL (rho=0.708). Our findings suggest that SGLT2 inhibitors induce minor changes in lipid profiles, with occasional cases of marked hypertriglyceridemia, and that dapagliflozin and ertugliflozin exhibit similar biochemical effects.

人们对接受钠-葡萄糖共转运体 2 抑制剂治疗的马匹的代谢和血脂状况还不甚了解。这项回顾性研究评估了高胰岛素血症马匹的血液参数，这些马匹每天口服一次ertugliflozin（0.05 mg/kg）或dapagliflozin（0.02 mg/kg）。在基线（第0天）和治疗7天和/或30天后采集血液样本。采用Wilcoxon符号秩检验、Mann-Whitney检验和Spearman秩相关检验进行统计分析。34匹马接受了达帕格列净治疗，24匹马接受了ertugliflozin治疗。第 0 天和第 30 天之间马匹内部的显著变化（p<0.05）包括[中位数，四分位数间距 (IQR)]：基础血清[胰岛素]（uU/ml）从 170（92-280）降至 28.7（14.5-90）；[甘油三酯]（mmol/l）从 0.5（0.3-0.6）升至 1.0（0.6-1.56），[β-羟丁酸]（umol/l）升至 0.30（0.24-0.35），[总胆固醇]（mmol/l）升至 2.36（2-2.6），[GGT]（IU/ml）升至 25（18-38）。高密度脂蛋白（HDL）占血清总脂类的百分比从 52.4% (47.9 %-61.0 %) 降至 50% (41 %-54.8 %)，极低密度脂蛋白（VLDL）从 10.4% (6.4 %-14.4 %) 升至 12.3% (9.9 %-16.8 %)（所有 p<0.05）。在第0天、第7天或第30天，ertugliflozin组和dapagliflozin组在这些参数上的差异均不显著。第 30 天，10/48 例（21%）患者的[甘油三酯]为 2.0 毫摩尔/升（最大值 = 10.8 毫摩尔/升）。第 30 天的[甘油三酯]与第 0 天的相关性：基础胰岛素（rho=0.47）；[甘油三酯]（rho=0.42）；%VLDL（rho=0.34）；第 30 天的相关性：[总胆固醇]（rho=0.67）、%HDL（rho=-0.432）和%VLDL（rho=0.708）。我们的研究结果表明，SGLT2 抑制剂会引起血脂谱的轻微变化，偶尔会出现明显的高甘油三酯血症，达帕格列酮和厄曲酶会产生类似的生化效应。

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引用次数: 0

Effect of short-term dopamine reduction on insulin sensitivity and post-prandial insulin and glucose responses in Standardbred horses 短期减少多巴胺对标准赛马胰岛素敏感性以及餐后胰岛素和葡萄糖反应的影响。

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-10-20 DOI: 10.1016/j.domaniend.2024.106893

Nicolas C. Galinelli , Nicholas J. Bamford , Madison L. Erdody , Tobias Warnken , Melody A. de Laat , Martin N. Sillence , Patricia A. Harris , Simon R. Bailey

The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis. The aim of this study was to investigate the effects of alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor that reduces dopamine production, on insulin sensitivity and the post-prandial insulin response to a glucose-containing meal. Six healthy Standardbred horses were enrolled in a placebo-controlled randomised crossover study, in which one dose of AMPT (40 mg/kg BW) or placebo was administered orally, prior to performing an in-feed oral glucose test (OGT) and a frequently sampled intravenous glucose tolerance test (FSIGTT). Dopamine reduction by AMPT was confirmed by an increase in plasma prolactin concentration and the lack of post-prandial increase in plasma dopamine concentration compared to placebo. Post-prandial insulin responses, both peak and AUCi, were increased after AMPT compared to placebo (P=0.048 and P=0.005, respectively), without affecting blood glucose concentrations. However, one dose of AMPT did not appear to affect tissue sensitivity as assessed by the FSIGTT. This study confirmed that dopamine plays a role in the regulation of insulin secretion in horses, as it does in other species, whereby the post-prandial release of dopamine into the circulation may inhibit pancreatic insulin secretion. Further studies are required to evaluate different dosing protocols for AMPT, and to further investigate the links between PPID, ID and laminitis risk in horses.

人们对多巴胺在调节马胰岛素分泌中的作用知之甚少，需要进一步研究。垂体中叶旁功能障碍（PPID）与多巴胺能神经元活性降低有关，多巴胺能神经元通常会抑制垂体中叶旁分泌肽类激素。患有 PPID 的马匹中有很大一部分还存在胰岛素失调（ID）问题，其特征是餐后高胰岛素血症和/或组织胰岛素抵抗，这些都是导致马蹄垫炎的危险因素。本研究旨在探讨α-甲基-para-酪氨酸（AMPT）（一种可减少多巴胺分泌的酪氨酸羟化酶抑制剂）对胰岛素敏感性和餐后胰岛素对含葡萄糖膳食反应的影响。六匹健康的标准赛马参加了一项安慰剂对照随机交叉研究，在进行进食口服葡萄糖试验（OGT）和频繁采样静脉葡萄糖耐量试验（FSIGTT）之前，口服一剂 AMPT（40 毫克/千克体重）或安慰剂。与安慰剂相比，AMPT 可使血浆催乳素浓度升高，且餐后血浆多巴胺浓度不升高，这证实了 AMPT 可减少多巴胺。与安慰剂相比，AMPT 可增加餐后胰岛素反应，包括峰值和 AUCi（分别为 P=0.048 和 P=0.005），但不影响血糖浓度。不过，一剂 AMPT 似乎不会影响 FSIGTT 评估的组织敏感性。这项研究证实，多巴胺在马的胰岛素分泌调节中发挥作用，在其他物种中也是如此，多巴胺在餐后释放到血液循环中可能会抑制胰岛素分泌。还需要开展进一步的研究，评估AMPT的不同剂量方案，并进一步调查马匹PPID、ID和蹄叶炎风险之间的联系。

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引用次数: 0

Effects of rumen metabolite butyric acid on bovine skeletal muscle satellite cells proliferation, apoptosis and transcriptional states during myogenic differentiation 瘤胃代谢物丁酸对牛骨骼肌卫星细胞增殖、凋亡和成肌分化过程中转录状态的影响

IF 1.9 2区农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Domestic animal endocrinology

Pub Date : 2024-10-11 DOI: 10.1016/j.domaniend.2024.106892

Xiao-Wei Wang , Yan-Ling Ding , Cheng-Long Li , Qing Ma , Yuan-Gang Shi , George E Liu , Cong-Jun Li , Xiao-Long Kang

Butyric acid, a pivotal short-chain fatty acid in rumen digestion, profoundly influences animal digestive and locomotor systems. Extensive research indicates its direct or indirect involvement in the growth and development of muscle and fat cells. However, the impact of butyric acid on the proliferation and differentiation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. This study aimed to elucidate the effects of butyrate on SMSCs proliferation and differentiation. After isolating, SMSCs were subjected to varying concentrations of sodium butyrate (NaB) during the proliferation and differentiation stages. Optimal treatment conditions (1 mM NaB for 2 days) were determined based on proliferative force, cell viability, and mRNA expression of proliferation and differentiation marker genes. Transcriptome sequencing was employed to screen for differential gene expression between 1 mM NaB-treated and untreated groups during SMSCs differentiation. Results indicated that lower NaB concentrations (≤1.0 mM) inhibited proliferation while promoting differentiation and apoptosis after a 2-day treatment. Conversely, higher NaB concentrations (≥2.0 mM) suppressed proliferation and differentiation and induced apoptosis. Transcriptome sequencing revealed differential expression of genes(ND1, ND3, CYTB, COX2, ATP6, MYOZ2, MYOZ3, MYBPC1 and ATP6V0A4,etc.) were associated with SMSCs differentiation and energy metabolism, enriching pathways such as Oxidative phosphorylation, MAPK, and Wnt signaling. These findings offer valuable insights into the molecular mechanisms underlying butyrate regulation of bovine SMSCs proliferation and differentiation, as well as muscle fiber type conversion in the future study.

丁酸是瘤胃消化过程中一种重要的短链脂肪酸，对动物的消化和运动系统有着深远的影响。大量研究表明，丁酸直接或间接参与了肌肉和脂肪细胞的生长和发育。然而，丁酸对牛骨骼肌卫星细胞（SMSCs）增殖和分化的影响仍不清楚。本研究旨在阐明丁酸对SMSCs增殖和分化的影响。分离SMSCs后，在增殖和分化阶段将其置于不同浓度的丁酸钠（NaB）中。根据增殖力、细胞活力以及增殖和分化标记基因的mRNA表达，确定了最佳处理条件（1 mM NaB 2天）。在 SMSCs 分化过程中，采用转录组测序筛选 1 mM NaB 处理组和未处理组之间的基因表达差异。结果表明，较低浓度的 NaB（≤1.0 mM）会抑制增殖，同时促进分化和凋亡。相反，较高浓度的 NaB（≥2.0 mM）会抑制增殖和分化，并诱导细胞凋亡。转录组测序显示，与SMSCs分化和能量代谢相关的基因（ND1、ND3、CYTB、COX2、ATP6、MYOZ2、MYOZ3、MYBPC1和ATP6V0A4等）表达存在差异，丰富了氧化磷酸化、MAPK和Wnt信号转导等通路。这些发现为今后研究丁酸盐调控牛SMSCs增殖和分化以及肌纤维类型转换的分子机制提供了有价值的见解。

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引用次数: 0