Parturition and Recruitment of Macrophages in Cervix of Mice Lacking the Prostaglandin F Receptor1

Yellon, Steven M.; Ebner, Charlotte A.; Sugimoto, Yukihiko

doi:10.1095/biolreprod.107.063404

Cited by 45 publications

(49 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present findings in Sham controls replicate our previous reports in both rats [5] and mice [32,40] for prepartum remodeling of cervix, in terms of hypertrophy, degradation of extracellular matrix, macrophage recruitment, and increased presence of nerve fibers. The function served by the pelvic nerve for some of these processes associated with parturition may differ from that mediated by the vagus nerve in innervation of the cervix.…”

Section: Discussionsupporting

confidence: 92%

“…With pregnancy, increased size of the cervix, indicated by reduced cell nuclei density, as well as reduced collagen content and structure, indicated by increased OD of birefringence from picrosirius red-stained sections, was the same in neurectomized rats as in Sham controls. Hypertrophy and reduced collagen matrix in the prepartum cervix in neurectomized rats that do not deliver on time is consistent with evidence that cervical remodeling occurs in PGF2a receptor-deficient mice, even though birth is delayed [40]. The finding that extracellular matrix degradation was not obstructed by neurectomy is also consistent with recent reports by Mackay et al [28] and Shi et al [35] who used light-induced autofluorescence to quantify collagen cross-linkage and evaluate cervical resistance to stretch.…”

Section: Discussionsupporting

confidence: 88%

“…Procedures used to stain cervical sections with picrosirius red for analysis of collagen content and structure, as well as to enumerate cell nuclei, macrophages, and nerve fibers, using immunohistochemistry and image analyses have been previously detailed [4,5,40]. Briefly, the optical density (OD) of polarized light from birefringence of type I collagen [13] from picrosirius red-stained sections of cervix was normalized to the number of cell nuclei/area for each rat, to account for the hypertrophy of tissue in pregnant rat cervix (less that of the extracellular matrix per field of view).…”

Section: Processing and Analysis Of Cervixmentioning

confidence: 99%

“…Photomicrographs of birefringent polarized light were converted to grayscale images. Regions of reduced collagen content and scattered fibrils were inversely related to OD as previously described [5,40] (details of NIH Image J analyses are in Materials and Methods). Compared to OD of nonpregnant controls, OD was significantly increased (less collagen content and structure) in cervix of prepartum [71] and postpartum (PP) groups (P , 0.05; ANOVA, F ¼ 5.984, df ¼ 11).…”

Section: Characteristics Of Remodeling Associated With Birthmentioning

confidence: 99%

See 3 more Smart Citations

Transection of the Pelvic or Vagus Nerve Forestalls Ripening of the Cervix and Delays Birth in Rats1

Clyde

Lechuga

Ebner

et al. 2011

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Innervation of the cervix is important for normal timing of birth because transection of the pelvic nerve forestalls birth and causes dystocia. To discover whether transection of the parasympathetic innervation of the cervix affects cervical ripening in the process of parturition was the objective of the present study. Rats on Day 16 of pregnancy had the pelvic nerve (PnX) or the vagus nerve (VnX) or both pathways (PnX+VnX) transected, sham-operated (Sham) or nonpregnant rats served as controls. Sections of fixed peripartum cervix were stained for collagen or processed by immunohistochemistry to identify macrophages and nerve fibers. All Sham controls delivered by the morning of Day 22 postbreeding, while births were delayed in more than 75% of neurectomized rats by more than 12 h. Dystocia was evident in more than 25% of the PnX and PnX+VnX rats. Moreover, on prepartum Day 21, serum progesterone was increased severalfold in neurectomized versus Sham rats. Assessments of cell nuclei counts indicated that the cervix of neurectomized rats and Sham controls had become equally hypertrophied compared to the unripe cervix in nonpregnant rats. Collagen content and structure were reduced in the cervix of all pregnant rats, whether neurectomized or Shams, versus that in nonpregnant rats. Stereological analysis of cervix sections found reduced numbers of resident macrophages in prepartum PnX and PnX+VnX rats on Day 21 postbreeding, as well as in VnX rats on Day 22 postbreeding compared to that in Sham controls. Finally, nerve transections blocked the prepartum increase in innervation that occurred in Sham rats on Day 21 postbreeding. These findings indicate that parasympathetic innervation of the cervix mediates local inflammatory processes, withdrawal of progesterone in circulation, and the normal timing of birth. Therefore, pelvic and vagal nerves regulate macrophage immigration and nerve fiber density but may not be involved in final remodeling of the extracellular matrix in the prepartum cervix. These findings support the contention that immigration of immune cells and enhanced innervation are involved in processes that remodel the cervix and time parturition.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Processing and Analysis Of Cervixmentioning

confidence: 99%

Section: Characteristics Of Remodeling Associated With Birthmentioning

confidence: 99%

See 2 more Smart Citations

Transection of the Pelvic or Vagus Nerve Forestalls Ripening of the Cervix and Delays Birth in Rats1

Clyde

Lechuga

Ebner

et al. 2011

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, in the cervix of prepartum PGR-BKO mice, collagenolytic processes that remodel the extracellular matrix of the cervix in preparation for birth were not affected by the lack of recruitment of neutrophils. These findings do not exclude the possibility that activation of a limited number of resident immune cells may drive increased production of prostaglandins, proinflammatory cytokines, and collagen degradation in the prepartum cervix at term [25,43,44] or are important for inflammation-induced preterm cervical remodeling [29,45]. Based upon the present findings in PGR-BKO mice, the PGR-B isoform is unlikely to be involved in such activational cascades that overcome the progestational protection of peak progesterone in circulation.…”

Section: Discussionmentioning

confidence: 56%

Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform

Yellon

Oshiro

Chhaya

et al. 2011

Biology of Reproduction

View full text Add to dashboard Cite

Withdrawal of progestational support for pregnancy is part of the final common pathways for parturition, but the role of nuclear progesterone receptor (PGR) isoforms in this process is not known. To determine if the PGR-B isoform participates in cervical remodeling at term, cervices were obtained from mice lacking PGR-B (PGR-BKO) and from wild-type (WT) controls before or after birth. PGR-BKO mice gave birth to viable pups at the same time as WT controls during the early morning of Day 19 postbreeding. Morphological analyses indicated that by the day before birth, cervices from PGR-BKO and WT mice had increased in size, with fewer cell nuclei/area as well as diminished collagen content and structure, as evidenced by optical density of picrosirius red-stained sections, compared to cervices from nonpregnant mice. Moreover, increased numbers of resident macrophages, but not neutrophils, were found in the prepartum cervix of PGR-BKO compared to nonpregnant mice, parallel to findings in WT mice. These results suggest that PGR-B does not contribute to the growth or degradation of the extracellular matrix or proinflammatory processes associated with recruitment of macrophages in the cervix leading up to birth. Rather, other receptors may contribute to the progesterone-dependent mechanism that promotes remodeling of the cervix during pregnancy and in the proinflammatory process associated with ripening before parturition.

show abstract

Differential outcomes of TLR2 engagement in inflammation-induced preterm birth

Cappelletti

Lawson

Chan

et al. 2017

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Preterm birth (PTB) is the leading cause of neonatal mortality worldwide. Infection and inflammation are considered main causes of PTB. Among multiple pathogens, Gram‐positive bacteria are commonly linked with induction of PTB. Although activation of innate immune responses, via TLR2 engagement, by Gram‐positive bacteria is a likely cause, whether induction of PTB depends on the potency of specific microbial components to induce Toll‐like receptor (TLR)2‐driven inflammation has not been elucidated. Here, we show that TLR2 activation by synthetic lipopeptides, Pam2Cys, and Pam3Cys specifically, variably influenced inflammation and subsequent induction of PTB. Pam2Cys challenge, compared to Pam3Cys, induced PTB and promoted significantly higher expression of inflammatory cytokines, specifically IL‐6 and IFN‐β, both in vivo and in vitro. Notably, antibody‐mediated neutralization of IL‐6 or genetic deletion of type I IFN receptor (IFNAR) was sufficient to protect from Pam2Cys‐driven PTB and to temper excessive proinflammatory cytokine production. Conversely, IFN‐β or IL‐6 was not sufficient to promote induction of PTB by Pam3Cys. In summary, our data implies a divergent function of TLR2‐activating lipopeptides in the magnitude and type of ligand‐driven inflammatory vigor in induction of PTB.

show abstract

Parturition and Recruitment of Macrophages in Cervix of Mice Lacking the Prostaglandin F Receptor1

Abstract: Parturition does not occur in transgenic mice lacking the prostaglandin F receptor (Ptgfr À/À

Cited by 45 publications

References 53 publications

Transection of the Pelvic or Vagus Nerve Forestalls Ripening of the Cervix and Delays Birth in Rats1

Transection of the Pelvic or Vagus Nerve Forestalls Ripening of the Cervix and Delays Birth in Rats1

Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform

Differential outcomes of TLR2 engagement in inflammation-induced preterm birth

Contact Info

Product

Resources

About