Dynamic cytokine interplay governing implantation and immune tolerance in pregnant pigs

Abstract

Embryo implantation in pigs represents a complex immunological and biochemical interaction between the developing conceptus and the maternal endometrium. The present study investigated temporal changes in key cytokines associated with successful implantation and early pregnancy in pigs. Twelve healthy sows (HDK75: 75% Hampshire x 25% local) were divided equally into pregnant and non-pregnant groups. Blood samples were collected from day 0 to day 42 post-insemination at weekly intervals, and plasma concentrations of cytokines--IFN-{gamma}, IFN-{beta}, IL-1, IL-1{beta}, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, and TNF- were quantified using ELISA.A significant (p < 0.05) progressive increase was observed in all cytokines in pregnant pigs, indicating active immunomodulation during early gestation. IFN-{gamma}, IL-1{beta}, and TNF- showed sharp elevations, reflecting their roles in endometrial receptivity, inflammation, and trophoblast invasion. Concurrently, IL-1RA, IL-4 and IL-10 exhibited marked increases, suggesting an anti-inflammatory shift crucial for maternal-fetal immune tolerance. The coordinated rise of IL-6, IL-8, IL-12, and IL-18 further indicated involvement in vascular remodeling and angiogenesis essential for placental development. In contrast, non-pregnant pigs displayed stable cytokine levels across all sampling points, confirming the absence of immune activation or inflammatory stimuli. These findings demonstrate that successful implantation in pigs is governed by a dynamic cytokine network balancing pro- and anti-inflammatory mediators. The interplay among these cytokines ensures immune tolerance, endometrial remodeling and vascular adaptation necessary for embryo attachment and maintenance of early pregnancy. The study highlights cytokine profiling as a potential biomarker approach for monitoring reproductive status in pigs.