The neurotrophin beta-nerve growth factor (NGF), which is present in the semen of different mammals, elicits potent ovulatory and luteotrophic actions in llamas following systemic administration. Here, we determine if purified NGF given intramuscularly (IM) during the preovulatory stage affects the corpus luteum (CL), hormone production, endometrial gene expression, and pregnancy rate of dairy heifers. Holstein-Friesian heifers were estrus-synchronized using estradiol benzoate (EB) plus an intravaginal progesterone (P4) device (DIB). After eight days, the device was removed and cloprostenol was given IM; the next day (day 9), heifers received EB IM plus one of the following: (i) 1 mg of NGF (NGF D9 group), (ii) 1 mg of NGF 32 h after EB (NGF D10 group), or (iii) phosphate buffer saline (control group). To measure pregnancy rates, heifers were treated similarly, then artificially inseminated with sexed semen 48–52 h after DIB removal, then an ultrasound was conducted 30 days after insemination. The females given NGF along with EB (NGF D9) showed significantly higher luteinizing hormone (LH) concentrations, larger CL vascular areas, and higher plasma P4 concentrations than the NGF D10 and control animals. Downregulation of the P4 receptor (PGR), and upregulation of both lipoprotein lipase (LPL) and Solute Carrier Family 6 member 14 (SLC6A14) endometrial genes, were detected in NGF D9 heifers. Furthermore, these heifers had a 10% higher pregnancy rate than the control group. We conclude that the higher P4 output, in response to the early NGF administration, led to the enhanced gene expression of transcripts related to uterine receptivity that may result in enhanced pregnancy rates.

The establishment of a state of immunotolerance in the female reproductive tract is important for embryo development, implantation and placentation. Llamas are induced ovulators and more than 98% of pregnancies occur in the left uterine horn. The objective of this study was to determine the uterine immune response of llamas in different stages of the reproductive cycle. Adult llamas (n = 20) were examined daily by transrectal ultrasonography to determine follicular growth and then randomly assigned to four groups: Follicular phase (n = 5); Luteal phase induced by an intramuscular administration of 50 ug of GnRH analogue (n = 5); Luteal phase induced by intrauterine infusion of seminal plasma (n = 5); and Luteal phase induced by mating (n = 5). Uterine fluid was collected separately from both uterine horns by non-surgical flushing to determine the presence of cells, total proteins and concentration of IL-1β, IL-6, IL-8, IFN γ, TNF-α and PGE2. Inflammatory cells were not observed in the uterine fluid and total protein pattern and inflammatory mediators did not differ between the left and the right horn amongst groups. Llamas treated with an intrauterine infusion of seminal plasma showed the highest concentration of total proteins, inflammatory cytokines PGE2, IL-8 and IL-1β in the uterine fluid. In conclusion, seminal plasma is made up of significant numbers of signaling molecules that are able to modify the uterine immune response in llamas.

Dogs can develop chronic inflammatory diseases that induce progressive tissue damage and illness. Delphinidin is a component of maqui (Aristotelia chilensis) and has anti-inflammatory and antioxidant effects. This study evaluated the immunomodulatory effects of delphinidin chloride (DC) and delphinidin-3-glucoside (D3G) on neutrophils and peripheral blood mononuclear cells (PBMCs) in dogs. Leukocytes were isolated from 20 clinically healthy dogs and treated with DC and D3G at concentrations of 50, 100, and 150 µM. The cells were then stimulated with lipopolysaccharide (LPS), platelet-activating factor (PAF), or phorbol 12-myristate 13-acetate (PMA) to evaluate cell viability, reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) formation, phagocytosis, chemotaxis, matrix metalloproteinase 9 (MMP-9) activity, and cytokine production. The results showed that both compounds preserved cell viability, significantly reducing ROS production and NET formation. DC significantly increased chemotaxis and D3G significantly reduced MMP-9 activity. Both compounds reduced the secretion of interleukin (IL) 1β (IL-1β) and tumor necrosis factor α (TNF-α) in neutrophils. In PBMCs, they decreased the production of IL-4 and IL-6 and modulated the production of interferon γ (IFN)-γ. In conclusion, delphinidin exerts selective anti-inflammatory activities in canine leukocytes, promoting inflammation resolution, suggesting its potential role as a nutraceutical for managing inflammatory pathologies in dogs.