Transforming growth factor-β1 disrupts angiogenesis during the follicular–luteal transition through the Smad–serpin family E member 1 (SERPINE1)/serpin family B member 5 (SERPINB5) signalling pathway in the cow

Intense angiogenesis is critical for the development of the corpus luteum and is tightly regulated by numerous factors. However, the exact role transforming growth factor beta 1 (TGFB1) plays during this follicular-luteal transition remains unclear. This study hypothesized that TGFB1 acting through TGFBR1 and Smad2/3 signaling would suppress angiogenesis during the follicular-luteal transition. Using a serum-free luteinizing follicular angiogenesis culture system, TGFB1 (1 and 10ng.mL-1) markedly disrupted the formation of capillary-like structures, reducing endothelial cell network area and number of branch points (P[less than]0.001). Furthermore, TGFB1 activated canonical Smad signaling and inhibited endothelial nitric oxide synthase (NOS3) mRNA expression, but up-regulated latent TGF-beta binding protein, type I TGFB receptor (TGFBR1), SERPINE1 and SERPINB5 mRNA expression. TGFBR1 inhibitor, SB431542, reversed the SERPINE1 and SERPINB5 up-regulation by TGFB1. Additionally, TGFB1 reduced progesterone synthesis through decreasing STAR, CYP11A1 and HSD3B1 expression. These results show that TGFB1 regulated NOS3, SERPINE1, and SERPINB5 expression via TGFBR1 and Smad2/3 signaling and could be the mechanism by which TGFB1 suppresses endothelial networks. Thereby, TGFB1 may provide a critical homeostatic control of angiogenesis during the follicular-luteal transition. Our findings reveal the molecular mechanisms underlying the actions of TGFB1 in early luteinization which may lead to novel therapeutic strategies to reverse luteal inadequacy

Efficacy of progesterone supplementation during early pregnancy in cows: a meta-analysis

Progesterone is a critical hormone during early pregnancy in the cow. As a result, a number of studies have investigated the effects of progesterone supplementation on pregnancy rates. In this study, a meta-analysis using a univariate binary random effects model was carried out on 84 specific treatments reported in 53 publications involving control (n = 9905) and progesterone-treated (n = 9135) cows. Although the results of individual studies showed wide variations (−40% to +50% point changes), progesterone treatment resulted in an overall increase in pregnancy rate odds ratio (OR = 1.12; P < 0.01). Improvements in pregnancy rate were only observed in cows treated at natural estrus (OR = 1.41, P < 0.01) and not following synchronization of estrus or ovulation. Although treatment between Days 3 to 7 postinsemination was beneficial (OR = 1.15; P < 0.01), treatment earlier or later than this was not. Progesterone supplementation was beneficial in cows of lower fertility (<45% control pregnancy rate) but not in cows with higher fertility. These results indicated that the benefit of progesterone supplementation on fertility of cows required exogenous progesterone supplementation to start between Day 3 to 7 and the appropriate reproductive status (i.e., lower fertility, natural estrus) of the treated cows

Suppression of Notch Signaling Stimulates Progesterone Synthesis by Enhancing the Expression of NR5A2 and NR2F2 in Porcine Granulosa Cells

The conserved Notch pathway is reported to be involved in progesterone synthesis and secretion; however, the exact effects remain controversial. To determine the role and potential mechanisms of the Notch signaling pathway in progesterone biosynthesis in porcine granulosa cells (pGCs), we first used a pharmacological &gamma;-secretase inhibitor, N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT), to block the Notch pathway in cultured pGCs and then evaluated the expression of genes in the progesterone biosynthesis pathway and key transcription factors (TFs) regulating steroidogenesis. We found that DAPT dose- and time-dependently increased progesterone secretion. The expression of steroidogenic proteins NPC1 and StAR and two TFs, NR5A2 and NR2F2, was significantly upregulated, while the expression of HSD3B was significantly downregulated. Furthermore, knockdown of both NR5A2 and NR2F2 with specific siRNAs blocked the upregulatory effects of DAPT on progesterone secretion and reversed the effects of DAPT on the expression of NPC1, StAR, and HSD3B. Moreover, knockdown of NR5A2 and NR2F2 stimulated the expression of Notch3. In conclusion, the inhibition of Notch signaling stimulated progesterone secretion by enhancing the expression of NPC1 and StAR, and the two TFs NR5A2 and NR2F2 acted as downstream TFs of Notch signaling in regulating progesterone synthesis

Wider Angle Egg Turning during Incubation Enhances Yolk Utilization and Promotes Goose Embryo Development

We aimed to investigate how wide-angle turning of eggs during incubation affected yolk utilization and the associated molecular mechanism, along with improved goose embryonic development. In total, 1152 eggs (mean weight: 143.33 ± 5.43 g) were divided equally and incubated in two commercial incubators with tray turning angles adjusted differently, to either 50° or 70°. Following incubation under the standard temperature and humidity level, turning eggs by 70° increased embryonic days 22 (E22), embryo mass, gosling weight at hatching, and egg hatchability, but reduced E22 yolk mass compared with those after turning eggs by 50°. Lipidomic analyses of the yolk revealed that egg turning at 70° reduced the concentrations of 17 of 1132 detected total lipids, including diglycerides, triglycerides, and phospholipids. Furthermore, the 70° egg turning upregulated the expression of genes related to lipolysis and fat digestion enzymes, such as lipase, cathepsin B, and prosaposin, as well as apolipoprotein B, apolipoprotein A4, very low-density lipoprotein receptor, low-density lipoprotein receptor-related protein 2, and thrombospondin receptor, which are genes involved in lipid transportation. Thus, a 70° egg turning angle during incubation enhances yolk utilization through the upregulation of lipolysis and fat digestion-related gene expression, thereby promoting embryonic development and improving egg hatchability and gosling quality

ROS-Induced GATA4 and GATA6 Downregulation Inhibits StAR Expression in LPS-Treated Porcine Granulosa-Lutein Cells

LPS is a major endotoxin produced by gram-negative bacteria, and exposure to it commonly occurs in animal husbandry. Previous studies have shown that LPS infection disturbs steroidogenesis, including progesterone production, and subsequently decreases animal reproductive performance. However, little information about the underlying mechanisms is available thus far. In the present study, an in vitro-luteinized porcine granulosa cell model was used to study the underlying molecular mechanisms of LPS treatment. We found that LPS significantly inhibits progesterone production and downregulates the expressions of progesterone synthesis-associated genes (StAR, CYP11A1, and 3β-HSD). Furthermore, the levels of ROS were significantly increased in an LPS dose-dependent manner. Moreover, transcriptional factors GATA4 and GATA6, but not NR5A1, were significantly downregulated. Elimination of LPS-stimulated ROS by melatonin or vitamin C could restore the expressions of GATA4, GATA6, and StAR. In parallel, StAR expression was also inhibited by the knockdown of GATA4 and GATA6. Based on these data, we conclude that LPS impairs StAR expression via the ROS-induced downregulation of GATA4 and GATA6. Collectively, these findings provide new insights into the understanding of reproductive losses in animals suffering from bacterial infection and LPS exposure

Fermented Feed Supplement Relieves Caecal Microbiota Dysbiosis and Kidney Injury Caused by High-Protein Diet in the Development of Gosling Gout

Firstly, forty-eight 1-day-old goslings were randomly allocated to four groups and were fed diets containing crude protein (CP) at different concentrations: 160, 180, 200, and 220 g/kg in Experiment One. We found a dose-dependent relationship between the dietary protein levels and morbidity of gosling gout. The concentration of serum uric acid (UA), creatinine (Cr), and urea nitrogen (UN), and the activity of xanthine oxidase in the 220CP groups were significantly higher than those in the low-protein diet groups. Beneficial microbes, including Akkermansia, Lactococcus, and Butyricicoccus were enriched in the ceca of healthy goslings, while the microbes Enterococcus, Enterobacteriaceae, and Bacteroides were enriched in those with gout. Then, we explored the effects of fermented feed on gosling gout caused by high-protein diets in Experiment Two. A total of 720 1-day-old goslings were randomly allotted to four experimental groups: CN (162.9 g/kg CP), CNF (167.5 g/kg CP, replacing 50 g/kg of the basal diet with fermented feed), HP (229.7 g/kg CP, a high-protein diet), and HPF (230.7 g/kg CP, replacing 50 g/kg of the high-protein diet with fermented feed). We found that the cumulative incidence of gout increased in the HP group compared with that in the control, but decreased in the HPF group compared to that in the HP group. Similarly, the concentration of serum UA in the HP group was higher than that in the CN group, but decreased in the HPF group. Meanwhile, compared with the HP group, using fermented feed in diets decreased the abundance of Enterococcus in the ceca of goslings, while increasing the abundance of Lactobacillus. These results suggest that appropriate dietary protein levels and the fermented feed supplement might relieve the kidney injury and gut microbiota dysbiosis caused by high-protein diets in the development of gosling gout

Effects of Caponization on Growth Performance and Carcass Composition of Yangzhou Ganders

In this study, we determined the effects of caponization on the growth performance and carcass traits of Yangzhou ganders. Fifty sham operated geese (the control group) and 80 caponized geese (the caponized group) were selected at 150 days of age and reared until 240 days of age. At 210 days of age, 30 geese from the caponized group were selected and fed with testosterone propionate (testosterone group). The results showed that caponization lowered testosterone and increased the total cholesterol and triglyceride concentrations in serum, live weights, average 15 day gains, and feed intake. Abdominal fat and intramuscular fat were significantly higher in the caponized geese than in the control at 240 days. Gene expression analysis showed that caponization promoted abdominal fat deposition and intermuscular fat content by upregulating the expression of adipogenic genes in the liver, adipose tissue, and muscle tissue. The high expression of SOCS3 in the hypothalamus, liver, and muscle of caponized geese suggests that caponization may lead to negative feedback regulation and leptin resistance. Changes in the expression of these genes, along with the downregulation of PAX3 in the breast muscle and MYOG in the leg muscles, indicate that caponization increases the live weight mainly by increasing fat deposition rather than muscle growth. These results expand our understanding of the mechanisms of caponization on growth performance and fat deposition in ganders