Expression of C–C motif chemokines and their receptors in bovine placentomes at spontaneous and induced parturition

Abstract

In bovine placentomes, the inflammatory response is considered important for the detachment of the fetal membrane from the caruncle after parturition. Glucocorticoids, a trigger of the onset of parturition, facilitate functional maturation of placentomes via prostaglandin (PG) and estrogen production in cattle. This study investigated how exogeneous glucocorticoids, which exert immunosuppressive effects, affect placental inflammation at parturition. Placentomes were collected immediately after spontaneous or induced parturition. Parturition was conventionally induced using PGF2α or dexamethasone or with a combination of triamcinolone acetonide and high-dose betamethasone (TABET treatment). Polymerase chain reaction (PCR) array analysis indicated that 9/13 CC motif chemokine ligands (CCLs) were upregulated > twofold in spontaneous parturition, with CCL2 and CCL8 being highly expressed. The expressions of CCL2, CCL8, CC motif chemokine receptor 1 (CCR1), and CCR5 in caruncles were significantly higher in spontaneous parturition than in induced parturition. Although the clinical dose of dexamethasone did not influence the expression of these CCLs and CCRs, TABET treatment increased CCR1 expression. CCL8, CCR1, CCR2, and CCR5 were localized in the caruncular epithelial cells. CCR2 was also localized in the epithelial cells of the cotyledonary villi. This study is the first report to reveal the disruption in CCL and CCR expression in bovine placentomes at induced parturition. Enhanced glucocorticoid exposure for the induction of parturition may upregulate CCR1 expression in placentomes, but the treatment does not adequately promote CCL expression. Additionally, immunohistochemistry suggested that the CCL-CCR system is involved in the functional regulation of maternal and fetal epithelial cells in placentomes at parturition.

Impaired placentomal interferon signaling as the possible cause of retained fetal membrane in parturition-induced cows

“…Although IFNT2-expressing cells in the caruncles were not identified in this study, we speculate that migrated macrophages from the maternal circulation into the caruncles might be a pivotal source of ligands that activate the IFN signaling pathway. This is consistent with our previous study showing that CD11B expression, a macrophage surface antigen, was increased in the caruncles during spontaneous parturition compared to induced parturition [ 21 ]. In addition, IFNA expression in this study, which is coordinately regulated with IFNT2 in PBL, did not increase in the placentomes during spontaneous parturition.…”

“…In this study, we revealed that enhanced glucocorticoid exposure in the TABET group normalized the expression of a substantial fraction of genes in the cotyledons. In contrast, this induction method did not upregulate CCL expression in the caruncles, suggesting that an inadequate inflammatory response may be an RFM factor in the TABET group [ 21 ]. Accordingly, the current study identified 774 DEGs in the caruncles of the TABET group.…”

“…Thus, we previously attempted to improve parturition induction in cows using a combination of the long-acting glucocorticoid, triamcinolone acetonide, with a high dose of betamethasone. This treatment reduced the number of trophoblast binucleate cells in placentomes at parturition [ 19 ] and upregulated the expression of placentome genes involved in PGE2 and androstenedione synthesis, but did not adequately promote the C–C motif chemokine ligand (CCL) expression [ 20 , 21 ]. Thus, although the improved induction method partially normalized the placentome function at parturition, the incidence of RFM remained high (33% to 78%).…”

Macrophages in bovine term placenta: An ultrastructural and molecular study

“…Our results on the maternal compartment of the bovine term placenta confirm the results from a previous study, asserted that during normal parturition, maternal macrophages are mostly pro‐inflammatory (Nelli et al., 2019). In a recent study (Hirayama et al., 2020), the mRNA expression of three inflammatory cytokines ( CCL2 , CCL5 , CCL8 ), two receptors ( CCR1 and CCR5 ) and a macrophage surface marker (CD11B) has been compared between cotyledon and caruncle tissues in spontaneously delivered foetal membranes. Interestingly, the expression of all six evaluated genes is higher in caruncular tissue compared to that of the cotyledon.…”

“…In a recent study (Hirayama et al, 2020), the mRNA expression of three inflammatory cytokines (CCL2, CCL5, CCL8), two receptors (CCR1 and CCR5) and a macrophage surface marker (CD11B) has been compared between cotyledon and caruncle tissues in spontaneously delivered foetal membranes. Interestingly, the expression of all six evaluated genes is higher in caruncular tissue compared to that of the cotyledon.…”