Residency and Activation of Myeloid Cells During Remodeling of the Prepartum Murine Cervix1

Payne, Kimberly J.; Clyde, Lindsey A.; Weldon, Abby J.; Milford, Terry‐Ann; Yellon, Steven M.

doi:10.1095/biolreprod.112.101840

Cited by 66 publications

(51 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Granulocytes, monocytes and some T cells infiltrate the human cervix during late gestation [32]. Monocytes seem to participate in the cervical remodeling before the onset of labor [33], granulocytes seem to play a key role at the postpartum period [34,35]; however, the T cell function is unclear. Recently, we demonstrated that T cells infiltrate the cervical zone of the fetal membranes during normal labor and that these cells are associated with MMP-9 [36,37], which also participates in surrounding tissue remodeling [38].…”

Section: Discussionmentioning

confidence: 99%

Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

Gomez‐Lopez

Tanaka

Zaeem

et al. 2013

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

Gomez‐Lopez

Tanaka

Zaeem

et al. 2013

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

show abstract

“…The BM-8 (F4/80) antibody was specific for macrophages because reports of cross-reactivity with other immune cells are not a consideration due to their absence or rare present in the murine cervix. 27 Brightfield scans of sections were taken (Aperio ImageScope). In a snapshot of a calibrated fields of view for each section (approximately 1.251×10 6 μm 3 ), cell nuclei and macrophages were counted.…”

Section: Methodsmentioning

confidence: 99%

Prevention of preterm birth by progestational agents: what are the molecular mechanisms?

Nold¹,

Maubert²,

Anton³

et al. 2013

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

OBJECTIVE Clinically, vaginal progesterone (VP) and 17 alpha-hydroxyprogestreone caproate (17P) have been shown to prevent preterm birth (PTB) in high risk populations. We hypothesize treatment with these agents may prevent PTB by altering molecular pathways involved in uterine contractility or cervical remodeling. STUDY DESIGN Using a mouse model, on days E14-E17 CD-1 pregnant mice were treated with either 1) 0.1cc of 25 mg/ml of 17P subcutaneously, 2) 0.1cc of castor oil subcutaneously, 3) 0.1 cc of 10 mg/ml of progesterone in Replens vaginally, or 4) 0.1cc of Replens vaginally, with four dams per treatment group. Mice were sacrificed six hours after treatment on E17.5. Cervices and uteri were collected for molecular analysis. RESULTS Exposure to VP significantly increased the expression of Defensin 1 compared to Replens (p<0.01) on E17.5. Neither VP nor 17P altered the expression of uterine contraction-associated proteins, progesterone mediated regulators of uterine quiescence, microRNAs involved in uterine contractility, or pathways involved in cervical remodeling. In addition, neither agent had an effect on immune cell trafficking or collagen content in the cervix. CONCLUSION Neither VP nor 17P had any effect on the studied pathways known to be involved in uterine contractility or quiescence. In the cervix, neither VP nor 17P altered pathways demonstrated to be involved in cervical remodeling. Administration of VP was noted to increase the expression of the antimicrobial protein Defensin 1. Whether this molecular change from VP results in a functional effect and is a key mechanism by which VP prevents PTB requires further study.

show abstract

“…31,51 During pregnancy at term, but before the onset of labor, women with a ripened cervix were found to have greater numbers of cervical macrophages in comparison to women who were not undergoing cervical ripening. 51 A murine model similarly found an increased proportion of macrophages in the cervix the day before birth (18 dpc) in comparison to mid/late gestation (15 dpc).…”

Section: Innate Immune Cells In Term and Preterm Labormentioning

confidence: 99%

Immune cells in term and preterm labor

et al. 2014

View full text Add to dashboard Cite

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm.

show abstract

Residency and Activation of Myeloid Cells During Remodeling of the Prepartum Murine Cervix1

Cited by 66 publications

References 42 publications

Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

Prevention of preterm birth by progestational agents: what are the molecular mechanisms?

Immune cells in term and preterm labor

Contact Info

Product

Resources

About