Abstract
BackgroundParturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift.MethodsTissues and blood were collected from pregnant Long-Evans rats on gestational days (GD) 17, 20 and 22 (term gestation). We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays.ResultsWe found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif) ligand 2 (Ccl2) gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif) ligand 1/CXCL1, and CXCL10) were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22.ConclusionMaternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.
Highlights
Parturition has been widely described as an immunological response; it is unknown how this is triggered
Among the most relevant we will mention three of them: chemokine (C-C motif) ligand 2 (CCL2) or monocyte chemotactic protein-1 (MCP-1) that participates in the monocyte recruitment, chemokine (C-X-C motif) ligand 1 (CXCL1) or neutrophil-activating protein 3 (NAP-3) that participates in the neutrophil recruitment, and CXCL10 or interferon gamma-induced protein 10 (IP-10) that participates in the T-cell recruitment [7,11]
We investigated the onset of peripheral leukocyte migration or chemotaxis during gestation in response to uterine and cervical extracts obtained at term (GD22)
Summary
Parturition has been widely described as an immunological response; it is unknown how this is triggered. Among the most relevant we will mention three of them: chemokine (C-C motif) ligand 2 (CCL2) or monocyte chemotactic protein-1 (MCP-1) that participates in the monocyte recruitment, chemokine (C-X-C motif) ligand 1 (CXCL1) or neutrophil-activating protein 3 (NAP-3) that participates in the neutrophil recruitment, and CXCL10 or interferon gamma-induced protein 10 (IP-10) that participates in the T-cell recruitment [7,11] Infiltrated leukocytes create this particular inflammatory stage, and along with maternal-fetal tissues, secrete other inflammatory mediators, including pro-inflammatory cytokines, prostaglandins and corticotrophin releasing hormone, that stimulate expression of uterine activation proteins (UAPs) [13]. The influence of progesterone (P4) in maintaining pregnancy and suppressing inflammation wanes and estradiol-17b (E2) levels rise [18,19], thereby permitting and accelerating the changes leading to parturition
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