Kisspeptin-10

Mammalian reproductive function is regulated by hypothalamic neurons that secrete Kisspeptin (Kp), a neuropeptide that stimulates gonadotropin-releasing hormone (GnRH) secretion, triggering pituitary gonadotrophins (LH and FSH) and gonadal steroids. This study evaluated the effect of Kisspeptin-10 (Kp10) on ovulation induction in rabbits, comparing its efficacy with that of the GnRH analogue gonadorelin. Multiparous New Zealand White × California does were assigned to three groups: control group (0.5 % saline solution, i.v.), GnRH group (20 μg gonadorelin, i.m.), and Kp10 group (250 μg Kp10, i.v.). Kp10 induced ovulation in 87.5 % of does, matching the response observed in the GnRH group, with a comparable number of corpora lutea (CL) per ovulated doe (12.9 ± 1.4 vs 14.6 ± 1.4 CL/doe, respectively). On day 7, plasma progesterone (P4) was significantly higher in ovulated GnRH-treated does than in Kp10-treated ones (25.12 ± 4.17 vs 9.47 ± 4.17 ng/mL; p < 0.0211), while non-ovulated controls exhibited minimal P4 concentrations (0.86 ± 0.12 ng/mL). Plasma estradiol (E2) levels showed no significant differences across days or groups, with mean values of 32.74 ± 4.33 pg/mL on day 0 and 37.27 ± 5.49 pg/mL on day 7, respectively. Histological analysis confirmed that Kp10 promoted preovulatory follicle development and CL formation, mirroring GnRH effects. Additionally, Kp10 enhanced angiogenesis, indicated by increased vascular endothelial growth factor (VEGF) expression in more developed follicles and CL. These results suggest that Kp10 could be an alternative to GnRH for ovulation induction in rabbits, although further studies are needed to explore optimal analogues, doses, and administration routes.

This study investigated the effects of Kisspeptin-10 (Kp-10) on HIV-1 Tat-induced blood-brain barrier (BBB) permeability and oxidative stress using both in vivo and in vitro models. In vivo, one hour after intraperitoneal administration of 50 nmol/kg (DSS)*6-Kp-10, mice were intravenously injected with HIV-1 Tat (100 μg/kg). Markers of oxidative stress, inflammatory cytokines, and BBB integrity were then evaluated. In vitro, bEnd.3 cells were treated with HIV-1 Tat and Kp-10, and endothelial permeability, Claudin-5 expression, and RhoA/ROCK signaling were assessed. HIV-1 Tat increased oxidative stress in the cortical tissue of mice, as evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) activity, glutathione peroxidase (GSH-Px) activity, and total antioxidant capacity (T-AOC). These effects were attenuated by Kp-10 administration. Additionally, Kp-10 suppressed the expression of pro-inflammatory cytokines, including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α), in response to HIV-1 Tat. Notably, Kp-10 mitigated HIV-1 Tat-induced BBB dysfunction by upregulating Claudin-5 expression in the cortical tissue of mice. In vitro, bEnd.3 cells were treated with HIV-1 Tat in the presence of Kp-10 at various concentrations. Our results demonstrated that Kp-10 prevented HIV-1 Tat-induced increases in trans-endothelial permeability and reductions in transepithelial electrical resistance (TEER) by upregulating Claudin-5 expression. Furthermore, Kp-10 inhibited the activation of the RhoA/Rho-associated protein kinase (RhoA/ROCK) signaling pathway in bEnd.3 cells. Overexpression of the RhoA-GTP Q63L mutant abolished the protective effects of Kp-10, suggesting that these effects are mediated through the RhoA/ROCK axis. These findings suggest that Kp-10 might be a potential therapeutic agent for HIV-associated neurocognitive disorders (HAND).