Macrophages in bovine term placenta: An ultrastructural and molecular study

Abstract

Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the foetal membranes at parturition. Our study aims to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. We used transmission electron microscopy (TEM), immunohistochemistry and semi‐quantitative RT‐PCR to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. Semi‐quantitative RT‐PCR was used to define macrophage polarization in foetal and maternal compartments of normal term placenta. Gene expression of factors involved in M1 polarization [interferon regulatory factor‐5 (IRF5), interleukin (IL)‐12A, IL12B] and in M2 polarization (IL10) were studied. Ultrastructurally, foetal macrophages showed an irregular shape and large vacuoles, whereas the maternal macrophages were spindle shaped. By immunohistochemistry, macrophages were identified by a strong staining with the lysosomal marker Lysosome‐associated membrane glycoprotein 1 (LAMP‐1), while myofibroblast in the maternal stroma was positive for alpha‐smooth muscle actin. We used the LAMP‐1 marker to compare the density of foetal stromal macrophages in placentas of cows with RFM and in controls, but no statistically significant difference was observed. RT‐PCR showed a higher expression of all studied genes in the maternal compartment of the placenta and generally a higher expression of M1‐, compared to M2‐associated genes. Our results indicated that at parturition placental macrophages predominantly show the pro‐inflammatory M1 polarization. The higher expression of all the target genes in the maternal compartment may denote that maternal macrophages in bovine term placenta are more frequent than foetal macrophages.

Utero-Placental Immune Milieu during Normal and Aglepristone-Induced Parturition in the Dog

“…In line with these observations in the dog, an increased infiltrate of macrophages in the feto-maternal interface has also been reported in humans, rats and cows [ 28 , 30 , 34 ]. However, the most prominent phenotypes of the invading macrophages in the dog appear to be mainly associated with tissue remodeling activities, contrasting with a higher prevalence of pro-inflammatory cells observed, e.g., in the cow [ 32 , 36 ], or humans, where cytokines related to M2 macrophages, such as IL10, are also downregulated [ 30 , 62 ].…”

“…In this regard, whereas macrophages with immunomodulatory and/or tissue remodeling activities (M2) are the predominant phenotype during the maintenance of pregnancy in humans, an increased presence of pro-inflammatory M1 macrophages (involved in Th1 response) appeared to be required for the initiation of parturition [ 30 ]. Similarly, in cattle, an increased utero-placental infiltrate of immune cells, involving M1 macrophages, neutrophils and T lymphocytes, is observed at the time of parturition [ 32 , 33 , 34 ]. Furthermore, an increased number of lymphocytes has been described in later stages of pregnancy in the interplacentomal epithelium of cows, ewes and deer [ 35 ].…”

Ultrastructural and Immunohistochemical Characterization of Maternal Myofibroblasts in the Bovine Placenta around Parturition

“…Formalin fixed paraffin embedded sections of all tissue samples were utilized for triple-colour IF staining, using first steps of a previously published immunohistochemistry procedure [ 51 ] followed by standard IF protocol [ 44 , 52 ]. Briefly, tissue was deparaffinized, rehydrated and washed under tap water for 5 min.…”

“…Accordingly, a previous study demonstrated that human placenta derived decidual stromal cells also show expression of VIM, α -SMA as well as representative ultrastructural similarities with myofibroblasts [ 7 ]. Similar to nuclear progesterone (P4) receptor (PGR) expressing decidual cells, which are described in invasive placentae, like in humans, rodents and dogs [ 39 , 40 , 41 , 42 , 43 ], there is also evidence of nuclear PGR expression in α -SMA positive cells in the caruncular stroma of bovine placenta throughout gestation and around parturition [ 44 , 45 ]. Altogether, it can be stated, that fibroblasts provide origin for different cells, including myofibroblasts and decidual cells in different species and placental types.…”

The Uterus as an Influencing Factor for Late Embryo/Early Fetal Loss—A Clinical Update

“…The precise mechanisms that lead to placental release are not well understood. Expulsion of fetal membranes involves multiple hormonal, physical and immunological changes [ 35 , 36 , 37 ]. Although retained placenta is a particularly predisposing factor for uterine infection [ 38 , 39 , 40 ], farm conditions along with cow factors of non-infectious cause and their interactions have been identified as main factors favoring this disorder [ 41 , 42 , 43 ].…”