Placentas associated with female neonates from pregnancies complicated by urinary tract infections have higher cAMP content and cytokines expression than males

• Published in: American journal of reproductive immunology (1989) Vol. 86; no. 3; pp. e13434 - n/a
• Main Authors: Olmos‐Ortiz, Andrea, Olivares‐Huerta, Alberto, García‐Quiroz, Janice, Zariñán, Teresa, Chavira, Roberto, Zaga‐Clavellina, Verónica, Avila, Euclides, Halhali, Ali, Durand, Marta, Larrea, Fernando, Díaz, Lorenza
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.09.2021
• Subjects: Antimicrobial peptides; Bacteriuria; cAMP; Cord blood; Cross-Sectional Studies; Cyclic AMP; Cyclic AMP - immunology; Cyclic AMP - metabolism; Cytokines; Cytokines - immunology; Defensins; Female; Fetuses; Humans; IL-1β; Immunoregulation; Infant, Newborn; Interleukin 1; Interleukin 10; Lipopolysaccharides; Male; Males; Neonates; Peptides; Placenta; Placenta - immunology; Placenta - metabolism; Pregnancy; Pregnancy Complications, Infectious - immunology; Pregnancy Complications, Infectious - metabolism; Radioimmunoassay; Sex Characteristics; sexual dimorphism; Trophoblasts; Urinary tract; Urinary tract diseases; urinary tract infection; Urinary tract infections; Urinary Tract Infections - immunology; Urinary Tract Infections - metabolism; Urogenital system; placenta; cAMP; sexual dimorphism; urinary tract infection; pregnancy
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.13434

Problem The cAMP pathway is involved in important biological processes including immune regulation and hormone signaling. At the feto‐maternal unit, cAMP participates in placental function/physiology and the establishment of immunoendocrine networks. Low cAMP in male fetuses cord blood has been linked to poorer perinatal outcomes; however, cAMP placental content and its relationship with immune factors and fetal sex in an infectious condition have not been investigated. Method of study Sex‐dependent changes in cAMP content and its association with cytokines and antimicrobial peptides expression were studied in human placentas collected from normal pregnancies and with urinary tract infections (UTI). Radioimmunoassay was used to quantify cAMP in placental tissue, while immune markers expression was studied by qPCR. Additionally, cAMP effect on antimicrobial peptides expression was studied in cultured trophoblasts challenged with lipopolysaccharide, to mimic an infection. Results In UTI, placentas from female neonates had higher cAMP tissue content and increased expression of TNFA, IL1B, and IL10 than those from males, where IFNG was more elevated. While cAMP negatively correlated with maternal bacteriuria and IFNG, it positively correlated with the antimicrobial peptide S100A9 expression in a sex‐specific fashion. In cultured trophoblasts, cAMP significantly stimulated β‐defensin‐1 while reduced the lipopolysaccharide‐dependent stimulatory effect on β‐defensin‐2, β‐defensins‐3, and S100A9. Conclusion Our results showed higher cAMP content and defense cytokines expression in placentas associated with female neonates from pregnancies complicated by UTI. The associations between cAMP and bacteriuria/immune markers, together with cAMP’s ability to differentially regulate placental antimicrobial peptides expression, suggest a dual modulatory role for cAMP in placental immunity.