Effects of ambient temperature on growth performance, slaughter traits, meat quality and serum antioxidant function in Pekin duck.

The present study investigated the effects of temperature on growth performance, slaughtering traits, meat quality and antioxidant function of Pekin ducks from 21-42 d of age. Single factor analysis of variance was used in this experiment, 144 21 d-old Pekin ducks were randomly allotted to 4 environmentally controlled chambers: T20 (20°C), T23 (23°C), T26 (26°C) and T29 (29°C), with 3 replicates in each group (12 ducks in each replicate), the relative humidity of all groups is 74%. During the 21-day trial period, feed and water were freely available. At 42 d, the BW (body weight) and ADG (average daily gain) of T26 were significantly lower than T20 (p < 0.05), and the T29 was significantly lower than T20 and T23 (p < 0.05). The ADFI (average daily feed intake) of T26 and T29 were significantly lower than T20 and T23 (p < 0.05). Compared to the T29, the T20 showed a significant increase oblique body length and chest width, and both the keel length and thigh muscle weight significantly increased in both the T20 and T23, while the pectoral muscle weight increased significantly in other groups (p < 0.05). The cooking loss of the T29 was the lowest (p < 0.05). The T-AOC (total antioxidant capacity) of T29 was significantly higher than the other groups (p < 0.05), the SOD (superoxide dismutase) in the T29 was significantly higher than the T23 and T26 (p < 0.05). In conditions of 74% relative humidity, the BW and ADFI of Pekin ducks significantly decrease when the environmental temperature exceeds 26°C, and the development of body size and muscle weight follows this pattern. The growth development and serum redox state of Pekin ducks are more ideal and stable at temperatures of 20°C and 23°C.

The Impact of Different Relative Humidity Levels on the Production Performance, Slaughter Performance, and Meat Quality of White Pekin Ducks Aged 4 to 42 Days.

This study aimed to investigate the effects of different humidity levels on the growth performance, slaughter performance, and meat quality of Pekin ducks through the artificial control of humidity, and to identify the suitable environmental humidity for Pekin duck growth. A completely randomized single-factor design was employed, selecting 144 newly hatched male Pekin ducks with healthy and similar BW (body weight) (60.92 g ± 4.38). These ducks were randomly assigned to four groups (A (RH (relative humidity) = 60%), B (RH = 67%), C (RH = 74%), D (RH = 81%)), with 12 ducks and 3 replicates in each group. The ducks were raised in a climate-controlled room for 42 days with ad libitum access to feed and water. BW and feed intake were measured every 3 days, and slaughter performance and meat quality were assessed at 42 days. There was no significant difference in the ADG (average daily gain) from 1 to 21 days (p > 0.05). The ADFI (average daily feed intake) of Group D was significantly lower than that of Groups A, B, and C (p < 0.05), with no significant differences between Groups A, B, and C (p > 0.05). At 42 days, the BW, ADG, and ADFI of Groups A and C were significantly higher than those of Group D (p < 0.05), with no significant differences among Groups A, B, and C (p > 0.05). Group C had a significantly higher breast muscle weight, breast muscle ratio, liver weight, and liver index than Groups B and D (p < 0.05), with no significant differences between Groups A, B, and D (p > 0.05). The meat shear force in Group C was significantly lower than that in Groups A, B, and D (p < 0.05). The L* (brightness) of Group C was significantly lower than that of Group A (p < 0.05), and the a* (redness) value of Group C was significantly higher than that of Groups A and B (p < 0.05), with no significant difference compared to Group D (p > 0.05). Group B had a significantly higher cooking loss than Groups A, C, and D (p < 0.05), with no significant differences among Groups A, C, and D (p > 0.05). Under 26 °C conditions, Pekin ducks perform best in terms of the production performance and feed efficiency, with high-quality meat, especially when reared at 74% humidity.

Dietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function.

Very-long-chain polyunsaturated fatty acids (VLCPUFAs; C24-38) constitute a unique class of PUFA that have important biological roles, but the lack of a suitable dietary source has limited research in this field. We produced an n-3 C24-28-rich VLCPUFA-oil concentrated from fish oil to study its bioavailability and physiological functions in C57BL/6J mice. The serum and retinal C24:5 levels increased significantly compared to control after a single-dose gavage, and VLCPUFAs were incorporated into the liver, brain, and eyes after 8-week supplementation. Dietary VLCPUFAs resulted in favorable cardiometabolic changes, and improved electroretinography responses and visual performance. VLCPUFA supplementation changed the expression of genes involved in PPAR signaling pathways. Further in vitro studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 are potent agonists for PPARs. The multiple potential beneficial effects of fish oil-derived VLCPUFAs on cardiometabolic risk and eye health in mice support future efforts to develop VLCPUFA-oil into a supplemental therapy.

Orthogonal Enzyme-Substrate Design Strategy for Discovery of Human Protein Palmitoyltransferase Substrates.

Protein palmitoylation, with more than 5000 substrates, is the most prevalent form of protein lipidation. Palmitoylated proteins participate in almost all areas of cellular physiology and have been linked to several human diseases. Twenty-three zDHHC enzymes catalyze protein palmitoylation with extensive overlap among the substrates of each zDHHC member. Currently, there is no global strategy to delineate the physiological substrates of individual zDHHC enzymes without perturbing the natural cellular pool. Here, we outline a general approach to accomplish this on the basis of synthetic orthogonal substrates that are only compatible with engineered zDHHC enzymes. We demonstrate the utility of this strategy by validating known substrates and use it to identify novel substrates of two human zDHHC enzymes. Finally, we employ this method to discover and explore conserved palmitoylation in a family of host restriction factors against pathogenic viruses, including SARS-CoV-2.

Synthesis and Evaluation of Fluorine-18-Labeled L-Rhamnose Derivatives.

The use of radiolabeled glucose for PET imaging resulted in the most commonly used tracer in the clinic, 2-deoxy-2-[18F]fluoroglucose (FDG). More recently, other radiolabeled sugars have been reported for various applications, including imaging tumors and infections. Therefore, in this study, we developed a series of fluorine-18-labeled L-rhamnose derivatives as potential PET tracers of various fungal and bacterial strains. Acetyl-protected triflate precursors of rhamnose were prepared and radiolabeled with fluorine-18 followed by hydrolysis to produce L-deoxy [18F]fluororhamnose. The overall radiochemical yield was 7-27% in a 90 min synthesis time with a radiochemical purity of 95%. In vivo biodistribution of the ligands using PET imaging showed that 2-deoxy-2-[18F]fluoro-L-rhamnose is stable for at least up to 60 min in mice and eliminated via renal clearance. The tracer also exhibited minimal tissue or skeletal uptake in healthy mice resulting in a low background signal.

Impact of Accessory Corpus Luteum Induced by Gonadotropin-Releasing Hormone or Human Chorionic Gonadotropin on Pregnancy Rates of Dairy Cattle following Embryo Transfer: A META-Analysis.

The circulation of progesterone (P4) concentrations of recipients has positive correlations with embryo survival and pregnancy success of embryo transfer (ET) in dairy cows. One strategy to improve P4 concentration is the administration of gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG), thereby inducing the formation of accessory corpus luteum (CL). This study aimed at determining the efficacy of GnRH or hCG treatment regarding embryo transfer (ET) and providing a better clinical veterinary practice guidance. A meta-analysis was conducted on the data from 2048 treated recipient cows and 1546 untreated cows. By inducing the formation of accessory CL with GnRH (100 µg), GnRH analogue Buserelin (8-10 µg), or hCG (≥1500 IU) 5-11 days after synchronized ovulation, hCG alone achieved an improvement (RR = 1.39, p < 0.05), while GnRH and GnRH analogue did not result in significant changes (RR = 1.04, p = 0.26). Treatment with GnRH or hCG 5-7 days after synchronized ovulation was associated with increased chances of pregnancy compared with later treatment (11-14 days). Owing to the treatment, the pregnancy rate of cows with very poor fertility (<40%) was improved, while that of cows with good fertility (≥40%) was not affected. Treatment with GnRH or hCG greatly improved pregnancy rates of parous lactating cows (RR = 1.32, p < 0.05) compared with heifers (RR = 1.02, p > 0.05). Additionally, as indicated by pregnancy loss analysis, the treatment had no benefit on late embryo/early fetus survival at days 28-81. In conclusion, the induction of accessory CL with GnRH or hCG may benefit fertility and have important implications for the management of reproductive performance in the dairy industry.

The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.

Huntington's disease is a neurodegenerative disorder caused by a CAG expansion in the first exon of the HTT gene, resulting in an extended polyglutamine (poly-Q) tract in huntingtin (httex1). The structural changes occurring to the poly-Q when increasing its length remain poorly understood due to its intrinsic flexibility and the strong compositional bias. The systematic application of site-specific isotopic labeling has enabled residue-specific NMR investigations of the poly-Q tract of pathogenic httex1 variants with 46 and 66 consecutive glutamines. Integrative data analysis reveals that the poly-Q tract adopts long α-helical conformations propagated and stabilized by glutamine side chain to backbone hydrogen bonds. We show that α-helical stability is a stronger signature in defining aggregation kinetics and the structure of the resulting fibrils than the number of glutamines. Our observations provide a structural perspective of the pathogenicity of expanded httex1 and pave the way to a deeper understanding of poly-Q-related diseases.

Bacterial lipopolysaccharide with different administration routes affects intestinal mucosal morphological, immunological, and microbial barrier functions in goslings.

The current study was conducted to evaluate the effects of different administration routes of bacterial lipopolysaccharide (LPS) on intestinal mucosal morphological, immunological, and microbial barrier functions in goslings. First, we compared intestinal villi morphology of goslings under intraperitoneal or oral LPS treatment through hematoxylin and eosin staining. Then, we determined the signatures of the microbiome in the ileum mucosa of goslings subjected to oral LPS treatment at 0, 2, 4, and 8 mg/kg BW by 16S sequencing, and analyzed the changes in intestinal barrier functions and permeability, levels of LPS in the ileum mucosa, plasma, and liver tissue, and the induced inflammatory response of Toll-like receptor 4 (TLR4). As a result, intraperitoneal LPS injection resulted in a thicker intestinal wall in the ileum within a short time, whereas villus height was less affected; in contrast, oral LPS treatment exerted a stronger influence on villus height but not on intestinal wall thickness. We also found that oral LPS treatment affected the structure of the intestinal microbiome, reflected by changes in the clustering of intestinal microbiota. The average abundance of Muribaculaceae showed an increasing trend with increasing LPS levels, and that of the genus Bacteroides decreased, compared with the control group. In addition, oral LPS treatment with 8 mg/kg BW affected the intestinal epithelial morphology, damage the mucosal immune barrier, downregulated the expression of tight junction proteins, increased circulating D-lactate levels, and stimulated the secretion of various inflammatory mediators and activation of the TLR4/MyD88/NFκB pathway. This study presented the injuries of intestinal mucosal barrier function induced by LPS challenges in goslings and provided a scientific model for searching the novel strategies to attenuate the immunological stress and gut injury caused by LPS.

A Possible Mechanism for Double-Yolked Eggs in the Early Stage of Egg-Laying in Zhedong White Goose-Function of IGF1 and LHR Signaling.

The cause of double-yolk (DY) egg production in birds is unclear, but it is related to body weight and adiposity. We explored the causes of the high proportion (up to 26%) of DY eggs in the first clutch of Zhedong white geese. We recorded the egg production of Zhedong white geese during the first egg-laying cycle and counted the proportion of DY eggs. We found that 30% of geese had 3 sets of double or triple follicles of the same diameter in the abdomen, which was close to the DY egg rate. In addition, the mRNA expression levels of the steroidogenic acute regulatory protein (StAR) and luteinizing hormone receptor (LHR) genes in granulosa cells were similar within the same set of follicles. Furthermore, the IGF1 concentration in geese that had at least 3 sets of follicles of the same diameter was significantly higher than that in birds with 0-1 set of follicles of the same diameter. Thus, we proposed that, in the first egg-laying stage of geese, high plasma concentrations of IGF1 stimulate the development of pre-hierarchal follicles and cause more than one follicle to be selected at the same time, mature at the same rate under the same gonadotrophin milieu, and ovulate at the same time to produce DY eggs.

Discovery of Novel Small-Molecule Scaffolds for the Inhibition and Activation of WIP1 Phosphatase from a RapidFire Mass Spectrometry High-Throughput Screen.

Wild-type P53-induced phosphatase 1 (WIP1), also known as PPM1D or PP2Cδ, is a serine/threonine protein phosphatase induced by P53 after genotoxic stress. WIP1 inhibition has been proposed as a therapeutic strategy for P53 wild-type cancers in which it is overexpressed, but this approach would be ineffective in P53-negative cancers. Furthermore, there are several cancers with mutated P53 where WIP1 acts as a tumor suppressor. Therefore, activating WIP1 phosphatase might also be a therapeutic strategy, depending on the P53 status. To date, no specific, potent WIP1 inhibitors with appropriate pharmacokinetic properties have been reported, nor have WIP1-specific activators. Here, we report the discovery of new WIP1 modulators from a high-throughput screen (HTS) using previously described orthogonal biochemical assays suitable for identifying both inhibitors and activators. The primary HTS was performed against a library of 102 277 compounds at a single concentration using a RapidFire mass spectrometry assay. Hits were further evaluated over a range of 11 concentrations with both the RapidFire MS assay and an orthogonal fluorescence-based assay. Further biophysical, biochemical, and cell-based studies of confirmed hits revealed a WIP1 activator and two inhibitors, one competitive and one uncompetitive. These new scaffolds are prime candidates for optimization which might enable inhibitors with improved pharmacokinetics and a first-in-class WIP1 activator.

Progression of prostate cancer reprograms MYC-mediated lipid metabolism via lysine methyltransferase 2A.

BACKGROUND: The activities of MYC, the androgen receptor, and its associated pioneer factors demonstrate substantial reprogramming between early and advanced prostate cancer. Although previous studies have shown a shift in cellular metabolic requirements associated with prostate cancer progression, the epigenetic regulation of these processes is incompletely described. Here, we have integrated chromatin immunoprecipitation sequencing (ChIP-seq) and whole-transcriptome sequencing to identify novel regulators of metabolism in advanced prostate tumors characterized by elevated MYC activity. RESULTS: Using ChIP-seq against MYC, HOXB13, and AR in LNCaP cells, we observed redistribution of co-bound sites suggestive of differential KMT2A activity as a function of MYC expression. In a cohort of 177 laser-capture microdissected foci of prostate tumors, KMT2A expression was positively correlated with MYC activity, AR activity, and HOXB13 expression, but decreased with tumor grade severity. However, KMT2A expression was negatively correlated with these factors in 25 LuCaP patient-derived xenograft models of advanced prostate cancer and 99 laser-capture microdissected foci of metastatic castration-resistant prostate cancer. Stratified by KMT2A expression, ChIP-seq against AR and HOXB13 in 15 LuCaP patient-derived xenografts showed an inverse association with sites involving genes implicated in lipid metabolism, including the arachidonic acid metabolic enzyme PLA2G4F. LuCaP patient-derived xenograft models grown as organoids recapitulated the inverse association between KMT2A expression and fluorine-18 labeled arachidonic acid uptake in vitro. CONCLUSIONS: Our study demonstrates that the epigenetic activity of transcription factor oncogenes exhibits a shift during prostate cancer progression with distinctive phenotypic effects on metabolism. These epigenetically driven changes in lipid metabolism may serve as novel targets for the development of novel imaging agents and therapeutics.

Immuno-Neutralization of Follistatin Bioactivity Enhances the Developmental Potential of Ovarian Pre-hierarchical Follicles in Yangzhou Geese.

In order to explore the role of follistatin (FST) in ovarian follicular development and egg production in Yangzhou geese, sixty-four egg laying geese of the same genetic origin were selected and divided into two groups with equal numbers. One group was immunized against the recombinant goose FST protein by intramuscular injection, whereas the control group received bovine serum albumin (BSA) injection. Immunization against FST significantly increased the number of pre-ovulatory follicles. Furthermore, immunization against FST upregulated Lhr, Star, Vldlr, Smad3, and Smad4 mRNA levels in the granulosa layer of pre-hierarchical follicles. The results suggest that FST plays a limiting role in the development of ovarian pre-hierarchical follicles into pre-ovulatory follicles by decreasing follicular sensitivity to activin in geese. The mechanism may be achieved by regulating the SMAD3 signaling pathway, which affects progesterone synthesis and yolk deposition in pre-hierarchical follicles.

Characterization of the roles of amphiregulin and transforming growth factor ß1 in microvasculature-like formation in human granulosa-lutein cells.

Vascular endothelial-cadherin (VE-cadherin) is an essential component that regulates angiogenesis during corpus luteum formation. Amphiregulin (AREG) and transforming growth factor ß1 (TGF-ß1) are two intrafollicular factors that possess opposite functions in directing corpus luteum development and progesterone synthesis in human granulosa-lutein (hGL) cells. However, whether AREG or TGF-ß1 regulates the VE-cadherin expression and subsequent angiogenesis in the human corpus luteum remains to be elucidated. Results showed that hGL cells cultured on Matrigel spontaneously formed capillary-like and sprout-like microvascular networks. Results of specific inhibitor treatment and small interfering RNA-mediated knockdown revealed that AREG promoteed microvascular-like formation in hGL cells by upregulating the VE-cadherin expression mediated by the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase1/2 (ERK1/2) signaling pathway. However, TGF-ß1 suppressed microvascular-like formation in hGL cells by downregulating VE-cadherin expression mediated by the activin receptor-like kinase (ALK)5-Sma- and Mad-related protein (SMAD)2/3/4 signaling pathway. Collectively, this study provides important insights into the underlying molecular mechanisms by which TGF-ß1 and AREG differentially regulate corpus luteum formation in human ovaries.

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.

The effects of dietary protein and fiber levels on growth performance, gout occurrence, intestinal microbial communities, and immunoregulation in the gut-kidney axis of goslings.

The current study evaluated the effects of dietary protein and fiber levels on growth performance, gout occurrence, intestinal microbial communities, and immunoregulation in the gut-kidney axis of goslings. A completely randomized 2 × 3 factorial design was adopted with 2 CP levels (180 [18CP] and 220 [22CP] g/kg) and 3 crude fiber (CF) levels (30 [low CF], 50 [mid CF], and 70 [high CF] g/kg). The high CP or low CF diets predisposed the goslings to gout. The high protein diets worsened renal function; serum concentrations of UA and Cr as well as XOD activity in 9-day-old goslings fed 22% CP diets were significantly increased. Although CF levels from 3 to 7% did not directly affect kidney health, increasing CF levels might accelerate the increase of probiotics in the cecum of goslings and withhold maleficent bacteria, alleviating the gut dysbiosis caused by high protein diets. An analysis of the cecal microbiota via 16Sr RNA sequencing revealed that the abundance of Enterococcus in the 22CP group was higher than that in the 18CP group but decreased with increasing CF levels on d 9. The abundance of Lactobacillus increased with increasing CF levels. Additionally, higher serum LPS and proinflammatory cytokine concentrations and upregulated mRNA expression levels in the cecal, tonsil, and kidney tissues indicated that high-protein diets could activate the TLR4/MyD88/NFκB pathway and induce both intestinal and renal inflammation in young goslings. Serum LPS concentrations on d 9 were found to decrease with increasing CF, although altering dietary CF levels did not directly affect the serum immune indices of goslings. In conclusion, the high CP diet exerted a negative effect on gout occurrence, microbial communities, and immunoregulation in the gut-kidney axis of goslings, while appropriately increased dietary fiber levels helped maintain intestinal balance and reduced serum LPS concentration. We propose a diet of 18% CP paired with a 5% CF as the optimal combination for gosling feed.

Targetable Conformationally Restricted Cyanines Enable Photon-Count-Limited Applications*.

Cyanine dyes are exceptionally useful probes for a range of fluorescence-based applications, but their photon output can be limited by trans-to-cis photoisomerization. We recently demonstrated that appending a ring system to the pentamethine cyanine ring system improves the quantum yield and extends the fluorescence lifetime. Here, we report an optimized synthesis of persulfonated variants that enable efficient labeling of nucleic acids and proteins. We demonstrate that a bifunctional sulfonated tertiary amide significantly improves the optical properties of the resulting bioconjugates. These new conformationally restricted cyanines are compared to the parent cyanine derivatives in a range of contexts. These include their use in the plasmonic hotspot of a DNA-nanoantenna, in single-molecule Förster-resonance energy transfer (FRET) applications, far-red fluorescence-lifetime imaging microscopy (FLIM), and single-molecule localization microscopy (SMLM). These efforts define contexts in which eliminating cyanine isomerization provides meaningful benefits to imaging performance.

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.

TGF-ß1 inhibits microvascular-like formation by decreasing VCAM1 and ICAM1 via the upregulation of SNAIL in human granulosa cells.

Three major endothelial cell junctional adhesion molecules (VCAM1, ICAM1 and E-SELECTIN) play important roles in the process of angiogenesis, a progression of extensive physiological vascularization that occurs during the formation of the corpus luteum. Our previous studies demonstrated that TGF-ß1 is a negative regulator of luteinization and progesterone production in luteinized human granulosa (hGL) cells. Whether TGF-ß1 can regulate the expression of these endothelial cell adhesion molecules and subsequent angiogenesis in hGL cells remains to be elucidated. Using dual inhibition approaches (small molecular inhibitors and siRNA-based knockdown), we provided the first data showing that TGF-ß1 significantly upregulates the expression of the SNAIL transcription factor, which in turn suppresses the expression of VCAM1 and ICAM1 in hGL cells. Additionally, we demonstrate that the suppressive effects on the expression of VCAM1 and ICAM1 induced by TGF-ß1 treatment were most likely via an ALK5-mediated SMAD-dependent signaling pathway. Furthermore, functional studies showed that hGL cells cultured on Matrigel exhibited two typical endothelial cell phenotypes, microvascular-like formation and a sprouting microvascular pattern. Notably, these phenotypes were significantly suppressed by either TGF-ß1 treatment or knockdown of VCAM1 and ICAM1. Our findings suggest that TGF-ß1 plays a potential role in the inhibition of granulosa cell angiogenesis by downregulating the expression of VCAM1 and ICAM1 during follicular development and corpus luteum formation.

Effects of immunization against inhibin α-subunit on ovarian structures, pregnancy rate, embryonic and fetal losses, and prolificacy rate in goats where estrus was induced during the non-breeding season.

The objectives of the study were to determine the dose-dependent effects of active immunization against inhibin α-subunit (AIINHA) on ovarian dynamics, concentrations of progesterone (P4), pregnancy rate (PR), embryonic and fetal losses (EFL), and prolificacy during the non-breeding season when there was imposing of a progestin-based treatment regimen to induce estrus in Beetal goats. Goats (n = 30) were randomly assigned into following groups: 1) saline (G-CON-0 mg; n = 10), 2) small dose (G-AIINHA-0.5 mg; n = 10), and 3) large dose (G-AIINHA-1 mg; n = 10). The primary administration of inhibin immunogen was administered at Day -48, followed by another administration at Day -20, and subsequently there was induction of estrus using a progestin based treatment regimen that included a single administration of progestin-containing sponge and PGF2α at Day -8. The sponge was removed, and GnRH was administered at Day -3 followed by breeding (Day 0) at standing estrus. Results indicated mean diameter of the follicles, size of pre-ovulatory follicles and corpora lutea, and post-breeding P4 concentrations were greater (P < 0.05) in the goat does of the G-AIINHA-0.5 than G-CON-0 group. The PR, and EFL, however, did not differ (P> 0.05) among groups, whereas prolificacy rate was greater (P = 0.04) in goat does of the G-AIINHA-0.5 than G-CON-0 groups. The data from this study indicate G-AIINHA-0.5 is the recommended dose of inhibin immunogen to enhance the reproductive performance during non-breeding season in Beetal goats when estrus is induced using a progestin-based treatment regimen.

Transforming growth factor-ß1 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-ß1 (TGFB1) plays during this follicular-luteal transition remains unclear. This study hypothesised that TGFB1, acting through TGFB receptor 1 (TGFBR1) and Smad2/3 signalling, would suppress angiogenesis during the follicular-luteal transition. Using a serum-free luteinising follicular angiogenesis culture system, TGFB1 (1 and 10ngmL-1 ) markedly disrupted the formation of capillary-like structures, reducing the endothelial cell network area and the number of branch points (P <0.001 compared with control). Furthermore, TGFB1 activated canonical Smad signalling and inhibited endothelial nitric oxide synthase (NOS3 ) mRNA expression, but upregulated latent TGFB-binding protein and TGFBR1 , serpin family E member 1 (SERPINE1 ) and serpin family B member 5 (SERPINB5 ) mRNA expression. SB431542, a TGFBR1 inhibitor, reversed the TGFB1-induced upregulation of SERPINE1 and SERPINB5 . In addition, TGFB1 reduced progesterone synthesis by decreasing the expression of steroidogenic acute regulatory protein (STAR ), cytochrome P450 family 11 subfamily A member 1 (CYP11A1 ) and 3ß-hydroxysteroid dehydrogenase (HSD3B1 ) expression. These results show that TGFB1 regulates NOS3 , SERPINE1 and SERPINB5 expression via TGFBR1 and Smad2/3 signalling and this could be the mechanism by which TGFB1 suppresses endothelial networks. Thereby, TGFB1 may provide critical homeostatic control of angiogenesis during the follicular-luteal transition. The findings of this study reveal the molecular mechanisms underlying the actions of TGFB1 in early luteinisation, which may lead to novel therapeutic strategies to reverse luteal inadequacy.