Conceptus-derived cytokines interleukin-1β and interferon-γ induce the expression of acute phase protein serum amyloid A3 in endometrial epithelia at the time of conceptus implantation in pigs

Abstract

Objective: Serum amyloid A3 (SAA3), an acute phase response protein, plays important roles in opsonization, antimicrobial activity, chemotactic activity, and immunomodulation, but its expression, regulation, and function at the maternal–conceptus interface in pigs are not fully understood. Therefore, we determined the expression of <i>SAA3</i> in the endometrium throughout the estrous cycle and at the maternal–conceptus interface during pregnancy.Methods: Endometrial tissues from pigs at various stages of the estrous cycle and pregnancy and with conceptuses derived from somatic cell nuclear transfer (SCNT), conceptus tissues during early pregnancy, and chorioallantoic tissues during mid- to late pregnancy were obtained and the expression of <i>SAA3</i> was analyzed. The effects of the steroid hormones, interleukin-1β (IL1B), and interferon-γ (IFNG) on the expression of <i>SAA3</i> were determined in endometrial explant cultures.Results: <i>SAA3</i> was expressed in the endometrium during the estrous cycle and pregnancy, with the highest level on day 12 of pregnancy. The expression of <i>SAA3</i> in the endometrium was significantly higher on day 12 of pregnancy than during the estrous cycle. Early-stage conceptuses and chorioallantoic tissues during mid to late pregnancy also expressed <i>SAA3</i>. The expression of <i>SAA3</i> was primarily localized to luminal epithelial cells in the endometrium. In endometrial explant cultures, the expression of <i>SAA3</i> was induced by increasing doses of IL1B and IFNG. Furthermore, the expression of <i>SAA3</i> decreased significantly in the endometria of pigs carrying conceptuses derived from SCNT on day 12 of pregnancy.Conclusion: These results suggest that the expression of <i>SAA3</i> in the endometrium during the implantation period increases in response to conceptus-derived IL1B and IFNG. The failure of those appropriate interactions between the implanting conceptus and the endometrium leads to dysregulation of endometrial <i>SAA3</i> expression, which could result in pregnancy failure. In addition, SAA3 could be a specific endometrial epithelial marker for conceptus implantation in pigs.