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

Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord

BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC) transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major challenges remain, especially with respect to the establishment of neuromuscular connections

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

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

Monochromatic Green Light Stimulation during Incubation Alters Hepatic Glucose Metabolism That Improves Embryonic Development in Yangzhou Goose Eggs

The influence of monochromatic green light stimulation on hatching performance and embryo development has been studied in chickens, but not geese. The liver has crucial functions in the regulation of energy metabolism during embryogenesis, but its involvement in green light transduction is still unidentified. We aimed to determine the influence of monochromatic green light on Yangzhou goose hatching performance and embryo development. We also investigated the metabolomics and transcriptomic responses of the embryonic liver to green light to determine the underlying molecular mechanisms. Eggs were incubated under either 12 h of monochromatic green light/dark (12 L:12D) cycles or 24 h of darkness (0G:24D). Green light promoted embryonic development and hatching performance, also affected the expression of myogenic regulatory factors associated with muscle development. It also shortened hatching time and elevated plasma levels of growth hormone and insulin-like growth factor-1. Metabolomics and transcriptomic results revealed differentially expressed genes and metabolites with enhanced gluconeogenesis/glycolysis and increased plasma glucose and pyruvate levels under green light. Hence, the growth-promoting effect possibly through regulating energy metabolism in the liver and myogenic regulatory factors in muscle. Our findings provide important and novel insights into the mechanisms underlying the beneficial effects of green light on goose embryos

Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-&tau; concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p &gt; 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques