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The contribution of the maternal immune system to the establishment of pregnancy in cattle.

Fair T - Front Immunol (2015)

Bottom Line: Immune cells play an integral role in affecting successful reproductive function.Key contributions of immune cell populations include granulocyte involvement in follicle differentiation and gamete transfer, monocyte invasion of the peri-ovulatory follicle and their subsequent role in corpus luteum formation and the pivotal roles of maternal macrophage and dendritic cells in key steps of the establishment of pregnancy, particularly, the maternal immune response to the embryo.These contributions are reviewed in detail below and key findings are discussed.

View Article: PubMed Central - PubMed

Affiliation: School of Agriculture and Food Sciences, University College Dublin , Dublin , Ireland.

ABSTRACT
Immune cells play an integral role in affecting successful reproductive function. Indeed, disturbed or aberrant immune function has been identified as primary mechanisms behind infertility. In contrast to the extensive body of literature that exists for human and mouse, studies detailing the immunological interaction between the embryo and the maternal endometrium are quite few in cattle. Nevertheless, by reviewing the existing studies and extrapolating from sheep, pig, mouse, and human data, we can draw a reasonably comprehensive picture. Key contributions of immune cell populations include granulocyte involvement in follicle differentiation and gamete transfer, monocyte invasion of the peri-ovulatory follicle and their subsequent role in corpus luteum formation and the pivotal roles of maternal macrophage and dendritic cells in key steps of the establishment of pregnancy, particularly, the maternal immune response to the embryo. These contributions are reviewed in detail below and key findings are discussed.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of dominant follicle differentiation and corpus luteum formation: follicle differentiation and luteinization appear to be characterized by three waves of immune cell infiltration. (A) Mast cell infiltration of the thecal cell layer (TC) triggered by increasing estradiol (E2) concentrations, note the intact basement membrane (BM) separating the follicle granulosa-cell layer (GC) and follicle contents [cumulus cell layer (CC), surrounding the oocyte (Oo), and the follicular fluid FF] from the ovarian stroma. (B) A peak in luteinizing hormone (LH) pulsatility triggers mast cell degranulation which stimulates the second wave through the direct and indirect actions of TNF-alpha (TNFA), a constituent of the granules. (C) The last wave is characterized by macrophage infiltration, possibly in response to E2 and other chemoattractants such as monocyte chemoattractant protein 1 (MCP1), acute phase proteins (APP), and GC derived oxidized low density lipoprotein (oxLDL). Note the expanded cumulus cells surrounding the metaphase II stage oocyte, there is a switch from E2 synthesis to progesterone synthesis as the follicular cells become luteinized. (D) Following ovulation, granulocytes, neutrophils, and eosinophils constitute the majority of immune cells within the developing corpus luteum (CL), with further infiltration of macrophages and endothelial cells as development and vascularization proceed. Macrophage derived tumor necrosis factor (TNF) is a potent stimulator of luteal prostaglandins (PG), including PGF2a, PGE2, and PG112, which in concert with TNF drive CL vascularization. Large luteal cells derived primarily from the granulosa cells produce the >80% of P4.
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Figure 1: Schematic diagram of dominant follicle differentiation and corpus luteum formation: follicle differentiation and luteinization appear to be characterized by three waves of immune cell infiltration. (A) Mast cell infiltration of the thecal cell layer (TC) triggered by increasing estradiol (E2) concentrations, note the intact basement membrane (BM) separating the follicle granulosa-cell layer (GC) and follicle contents [cumulus cell layer (CC), surrounding the oocyte (Oo), and the follicular fluid FF] from the ovarian stroma. (B) A peak in luteinizing hormone (LH) pulsatility triggers mast cell degranulation which stimulates the second wave through the direct and indirect actions of TNF-alpha (TNFA), a constituent of the granules. (C) The last wave is characterized by macrophage infiltration, possibly in response to E2 and other chemoattractants such as monocyte chemoattractant protein 1 (MCP1), acute phase proteins (APP), and GC derived oxidized low density lipoprotein (oxLDL). Note the expanded cumulus cells surrounding the metaphase II stage oocyte, there is a switch from E2 synthesis to progesterone synthesis as the follicular cells become luteinized. (D) Following ovulation, granulocytes, neutrophils, and eosinophils constitute the majority of immune cells within the developing corpus luteum (CL), with further infiltration of macrophages and endothelial cells as development and vascularization proceed. Macrophage derived tumor necrosis factor (TNF) is a potent stimulator of luteal prostaglandins (PG), including PGF2a, PGE2, and PG112, which in concert with TNF drive CL vascularization. Large luteal cells derived primarily from the granulosa cells produce the >80% of P4.

Mentions: Taken together, pre-ovulatory follicle differentiation and luteinization appear to be characterized by three phases of immune cell infiltration, which are illustrated in Figure 1: histological analysis of bovine dominant follicles shows that mast cell infiltration of the theca layer constitutes the first phase (5) (Figure 1A), luteinizing hormone (LH) triggered degranulation of the mast cells stimulates the second phase through the direct and indirect actions of TNF-alpha (TNFA), a constituent of the granules (Figure 1B). The second phase has been characterized in sheep and pigs as an influx of eosinophilic and neutrophilic granulocytes and T-lymphocytes (6, 7). The last phase of leukocyte migration consists of phagocytic monocytes (Mo); MΦ’s increase in the sow and ewe follicles at the time of ovulation (6, 7) (Figure 1C), possibly in response to peak estradiol concentrations (8). The temporal changes in the influx of leukocytes appear to occur in response to various chemoattractant cues produced by the developing follicle (9), indeed leukocyte chemoattractant activity has been demonstrated in bovine, ovine, and human follicular fluid of ovulatory follicles (10–12). Immunohistochemical characterization of the immune cell repertoire of the bovine ovary has largely focused on the formation and regression of the CL, which will be discussed later. In contrast, there are many reports detailing the transcriptomic profile of ovarian follicle development in cattle: (13–19). In particular, the deep sequencing analysis of bovine follicular theca and granulosa tissue during pre-ovulatory follicle development, revealed a profound effect of ovarian follicle stage on the expression of many genes within immune-related pathways in these tissues: during follicle differentiation, bovine thecal tissue was characterized by the expression of immune factors associated with vascularization, angiogenesis, and cellular proliferation (15, 20), processes which are carried out by MΦ’s in the theca layer during this time (21, 22). The bovine transcriptomic data also concurred with the histological findings described for sheep and pigs, as factors with known inflammatory/chemotactic properties such as AKT2, ARHGEF1, GNAI2, IL-1, IL-6, and IL-8b (23–25) were upregulated and pathways associated with MΦ and neutrophil function were overpopulated in differentiating thecal tissue (15).


The contribution of the maternal immune system to the establishment of pregnancy in cattle.

Fair T - Front Immunol (2015)

Schematic diagram of dominant follicle differentiation and corpus luteum formation: follicle differentiation and luteinization appear to be characterized by three waves of immune cell infiltration. (A) Mast cell infiltration of the thecal cell layer (TC) triggered by increasing estradiol (E2) concentrations, note the intact basement membrane (BM) separating the follicle granulosa-cell layer (GC) and follicle contents [cumulus cell layer (CC), surrounding the oocyte (Oo), and the follicular fluid FF] from the ovarian stroma. (B) A peak in luteinizing hormone (LH) pulsatility triggers mast cell degranulation which stimulates the second wave through the direct and indirect actions of TNF-alpha (TNFA), a constituent of the granules. (C) The last wave is characterized by macrophage infiltration, possibly in response to E2 and other chemoattractants such as monocyte chemoattractant protein 1 (MCP1), acute phase proteins (APP), and GC derived oxidized low density lipoprotein (oxLDL). Note the expanded cumulus cells surrounding the metaphase II stage oocyte, there is a switch from E2 synthesis to progesterone synthesis as the follicular cells become luteinized. (D) Following ovulation, granulocytes, neutrophils, and eosinophils constitute the majority of immune cells within the developing corpus luteum (CL), with further infiltration of macrophages and endothelial cells as development and vascularization proceed. Macrophage derived tumor necrosis factor (TNF) is a potent stimulator of luteal prostaglandins (PG), including PGF2a, PGE2, and PG112, which in concert with TNF drive CL vascularization. Large luteal cells derived primarily from the granulosa cells produce the >80% of P4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309202&req=5

Figure 1: Schematic diagram of dominant follicle differentiation and corpus luteum formation: follicle differentiation and luteinization appear to be characterized by three waves of immune cell infiltration. (A) Mast cell infiltration of the thecal cell layer (TC) triggered by increasing estradiol (E2) concentrations, note the intact basement membrane (BM) separating the follicle granulosa-cell layer (GC) and follicle contents [cumulus cell layer (CC), surrounding the oocyte (Oo), and the follicular fluid FF] from the ovarian stroma. (B) A peak in luteinizing hormone (LH) pulsatility triggers mast cell degranulation which stimulates the second wave through the direct and indirect actions of TNF-alpha (TNFA), a constituent of the granules. (C) The last wave is characterized by macrophage infiltration, possibly in response to E2 and other chemoattractants such as monocyte chemoattractant protein 1 (MCP1), acute phase proteins (APP), and GC derived oxidized low density lipoprotein (oxLDL). Note the expanded cumulus cells surrounding the metaphase II stage oocyte, there is a switch from E2 synthesis to progesterone synthesis as the follicular cells become luteinized. (D) Following ovulation, granulocytes, neutrophils, and eosinophils constitute the majority of immune cells within the developing corpus luteum (CL), with further infiltration of macrophages and endothelial cells as development and vascularization proceed. Macrophage derived tumor necrosis factor (TNF) is a potent stimulator of luteal prostaglandins (PG), including PGF2a, PGE2, and PG112, which in concert with TNF drive CL vascularization. Large luteal cells derived primarily from the granulosa cells produce the >80% of P4.
Mentions: Taken together, pre-ovulatory follicle differentiation and luteinization appear to be characterized by three phases of immune cell infiltration, which are illustrated in Figure 1: histological analysis of bovine dominant follicles shows that mast cell infiltration of the theca layer constitutes the first phase (5) (Figure 1A), luteinizing hormone (LH) triggered degranulation of the mast cells stimulates the second phase through the direct and indirect actions of TNF-alpha (TNFA), a constituent of the granules (Figure 1B). The second phase has been characterized in sheep and pigs as an influx of eosinophilic and neutrophilic granulocytes and T-lymphocytes (6, 7). The last phase of leukocyte migration consists of phagocytic monocytes (Mo); MΦ’s increase in the sow and ewe follicles at the time of ovulation (6, 7) (Figure 1C), possibly in response to peak estradiol concentrations (8). The temporal changes in the influx of leukocytes appear to occur in response to various chemoattractant cues produced by the developing follicle (9), indeed leukocyte chemoattractant activity has been demonstrated in bovine, ovine, and human follicular fluid of ovulatory follicles (10–12). Immunohistochemical characterization of the immune cell repertoire of the bovine ovary has largely focused on the formation and regression of the CL, which will be discussed later. In contrast, there are many reports detailing the transcriptomic profile of ovarian follicle development in cattle: (13–19). In particular, the deep sequencing analysis of bovine follicular theca and granulosa tissue during pre-ovulatory follicle development, revealed a profound effect of ovarian follicle stage on the expression of many genes within immune-related pathways in these tissues: during follicle differentiation, bovine thecal tissue was characterized by the expression of immune factors associated with vascularization, angiogenesis, and cellular proliferation (15, 20), processes which are carried out by MΦ’s in the theca layer during this time (21, 22). The bovine transcriptomic data also concurred with the histological findings described for sheep and pigs, as factors with known inflammatory/chemotactic properties such as AKT2, ARHGEF1, GNAI2, IL-1, IL-6, and IL-8b (23–25) were upregulated and pathways associated with MΦ and neutrophil function were overpopulated in differentiating thecal tissue (15).

Bottom Line: Immune cells play an integral role in affecting successful reproductive function.Key contributions of immune cell populations include granulocyte involvement in follicle differentiation and gamete transfer, monocyte invasion of the peri-ovulatory follicle and their subsequent role in corpus luteum formation and the pivotal roles of maternal macrophage and dendritic cells in key steps of the establishment of pregnancy, particularly, the maternal immune response to the embryo.These contributions are reviewed in detail below and key findings are discussed.

View Article: PubMed Central - PubMed

Affiliation: School of Agriculture and Food Sciences, University College Dublin , Dublin , Ireland.

ABSTRACT
Immune cells play an integral role in affecting successful reproductive function. Indeed, disturbed or aberrant immune function has been identified as primary mechanisms behind infertility. In contrast to the extensive body of literature that exists for human and mouse, studies detailing the immunological interaction between the embryo and the maternal endometrium are quite few in cattle. Nevertheless, by reviewing the existing studies and extrapolating from sheep, pig, mouse, and human data, we can draw a reasonably comprehensive picture. Key contributions of immune cell populations include granulocyte involvement in follicle differentiation and gamete transfer, monocyte invasion of the peri-ovulatory follicle and their subsequent role in corpus luteum formation and the pivotal roles of maternal macrophage and dendritic cells in key steps of the establishment of pregnancy, particularly, the maternal immune response to the embryo. These contributions are reviewed in detail below and key findings are discussed.

No MeSH data available.


Related in: MedlinePlus