A proteomic profile of postpartum cervical repair in mice

Abstract

A timely and complete uterine cervical tissue repair postpartum is of necessity to prevent obstetrical complications, such as cervicitis, ectropion, hemorrhage, repeated miscarriages or abortions and possibly preterm labor and malignancies. We recently characterized the morphological alterations, as well as changes in angiogenic expression profile in a mice uterine cervix during the immediate postpartum period. Here, we build on this previous study using a proteomic analysis to profile postpartum tissue changes in mice cervix during the same period, the first 48 h of postpartum. The current proteomics data reveal a variable expression of several intermediate filaments, cytoskeletal modulators and proteins with immune and/or wound-healing properties. We conclude that postpartum cervical repair involves a rapid and tightly regulated balance between a host of biological factors, notably between anti- and pro-inflammatory factors, executed by the M1 and M2 macrophage cells, as revealed by proteomics and verified by confocal immunofluorescence. Future studies will assess the suitability of some of the key proteins identified in this study as potential markers for determining the phase of postpartum cervical repair in obstetrical complications, such as cervical lacerations.

Immunobiology of Cervix Ripening

“…Recovery during phase 4 of remodeling is essential for restoration of the barrier function of the cervix. This nonscaring process occurs rapidly in rodents within 2 days of birth in preparation for a postpartum estrus and the next pregnancy (112). Expression of message for molecules in the cervix during this period are associated with inflammatory and wound-healing functions.…”

Evidence of macrophage modulation in the mouse pubic symphysis remodeling during the end of first pregnancy and postpartum

“…As suggested by integrated data from gene and protein expression studies of cervical modifications at pregnancy and postpartum 51,52 , these similar essays may also help us to understand the immunological processes involved in mouse PS complex ECM remodeling at first pregnancy. Previous data 36,42 , along with our morphological analysis, support that immune system processes are statistically significant along with IpL remodeling by the enrichment analysis of microarray and proteomic experiments.…”

Mechanobiology of mice cervix: expression profile of mechano-related molecules during pregnancy

“…This speculation is supported by our recent proteomic findings revealing that mechano-related proteins are the most abundantly expressed of all proteins in the mouse cervix. This is particularly notable as fetal-induced forces exerted on the cervix increase during pregnancy and their (mechanical-related molecules) levels revert back after births, following removal of fetal force (Schwabe et al 2014, Stanley et al 2018).…”

“…i) Tissue Processing: Harvested tissues were immediately fixed in 10% formalin for 48 h, dehydrated and embedded in paraffin wax. The embedded tissues were later sectioned at 5 m, and the sections were processed for confocal immunofluorescence, as described previously (Donnelly et al, 2013, Stanley et al, 2015, 2018.…”

“…Cervical remodeling (CR) is a complex biological process involving multiple factors (Jorge et al 2014, Mahendroo 2012, Holt et al 2011, Timmons et al 2010. Most of our previous studies of CR regulation have focused on chemical cues, such as sex steroid hormones and growth factors (Stanley et al 2015, 2018, Zhao et al 2013, Donnelly et al 2013. However, more recently we used a proteome-wide technology to provide the first evidence of the presence and expression profile of mechanorelated signaling molecules in the mouse cervix during pregnancy and cervical repair (Schwabe et al 2014, Stanley et al 2018.…”