Decidualization in the post-partum uterus of the mouse

Brandon, Janet M.

doi:10.1530/jrf.0.0880151

Cited by 10 publications

(9 citation statements)

References 10 publications

(16 reference statements)

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“…1). Further, implantation of embryos in subsequent pregnancies will not occur in the vicinity of nodule cells, which are also associated with a reduced decidualization response (49). Interestingly, induction of in vivo decidualization was associated with enhanced expression of macrophage and lymphocyte chemoattractants Csf1 and Cxcl12 , along with the Cxcl12 receptor Cxcr4 (Fig.…”

Section: Resultsmentioning

confidence: 99%

RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss

Strug

Kim

et al. 2018

FASEB j.

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Unexplained recurrent pregnancy loss (uRPL) is associated with repeated embryo loss and endometrial repair with elevated endometrial expression of inflammatory cytokines, including IFN-γ. Notch signaling through its transcription factor recombination signal binding protein Jκ (RBPJ) regulates mechanisms including the immune response and repair after tissue injury. Initially, null mutation of RBPJ in the mouse uterus ( PgrRbpj; Rbpj c-KO) results in subfertility, but we have found that these mice become infertile after pregnancy as a result of dysfunctional postpartum uterine repair, including delayed endometrial epithelial and myometrial regeneration. RNA sequencing of postpartum uterine repair sites revealed global up-regulation of inflammatory pathways, including IFN signaling. Consistent with elevated IFN-γ, macrophages were recruited and polarized toward an M1-cytotoxic phenotype, which is associated with preventing repair and promoting further tissue injury. Through embryo transfer experiments, we show that dysfunctional postpartum repair directly impairs future embryo implantation in Rbpj c-KO mice. Last, we clinically correlated our findings from the Rbpj c-KO mouse in women diagnosed with uRPL. Reduced RBPJ in women with uRPL was associated with increased levels of IFN-γ. The data, taken together, indicate that RBPJ regulates inflammation during endometrial repair, which is essential for future pregnancy potential, and its dysregulation may serve as an unidentified contributor to uRPL in women.-Strug, M. R., Su, R.-W., Kim, T. H., Mauriello, A., Ticconi, C., Lessey, B. A., Young, S. L., Lim, J. M., Jeong, J.-W., Fazleabas, A. T. RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss.

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Section: Resultsmentioning

confidence: 99%

RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss

Strug

Kim

et al. 2018

FASEB j.

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“…Importantly, most wounds heal with scarring, whereas endometrial repair occurs without scarring, which otherwise occurs only during fetal development. However, in one study in the postpartum mouse [61] endometrial 'nodules' have been reported.…”

Section: Discussionmentioning

confidence: 96%

Matrix Metalloproteinases in Endometrial Breakdown and Repair: Functional Significance in a Mouse Model1

Kaitu'u

Shen²,

Zhang³

et al. 2005

Biology of Reproduction

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Considerable correlative evidence suggests an important role for matrix metalloproteinases (MMPs) in menstruation, a process which occurs naturally in very few species. In this study, MMP expression was examined in a mouse model of endometrial breakdown and repair and the functional importance of MMPs determined. In the model, progesterone support was withdrawn from mice in which endometrial decidualization had been induced; 24 h later, endometrial breakdown was complete, and the entire decidual zone had been shed. Re-epithelialization had occurred by 36 h, and the endometrium had undergone extensive restoration toward a predecidualized state by 48 h. Immunoreactive MMP9 and MMP7 colocalized with leukocyte subsets, particularly neutrophils, whereas MMP13 staining was always extracellular. MMP3 and MMP7 were abundant during re-epithelialization in close proximity to newly reforming epithelium. The functional importance of MMPs in these processes was examined using two MMP inhibitors, doxycycline and batimistat. Both inhibitors effectively reduced MMP activity, as assessed by in situ zymography, but did not have significant effects on endometrial breakdown or repair. This study demonstrates that although MMPs are present in abundance during endometrial breakdown and repair in this mouse model, they are not the key mediators of these processes.

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“…On day 4 postcoitus, artificial decidualization with separated deciduoma was induced with a modified protocol by infusion of 1 μl of sesame oil (the previous standard protocol used 10 μl of oil (17)) into one uterine lumen, whereas the contralateral horn without any treatment served as control. The oil-induced deciduoma were detected on day 6 by the blue dye method as described above.…”

Section: Methodsmentioning

confidence: 99%

Transient β2-Adrenoceptor Activation Confers Pregnancy Loss by Disrupting Embryo Spacing at Implantation

Chen

Zhang

Peng

et al. 2011

Journal of Biological Chemistry

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Pregnancy loss is a serious social and medical issue, with one important cause associated with aberrant embryo implantation during early pregnancy. However, whether and how the process of embryo implantation is affected by environmental factors such as stress-induced sympathetic activation remained elusive. Here we report an unexpected, transient effect of β2-adrenoreceptor (β2-AR) activation (day 4 postcoitus) in disrupting embryo spacing at implantation, leading to substantially increased midterm pregnancy loss. The abnormal embryo spacing could be prevented by pretreatment of β2-AR antagonist or genetic ablation of β-AR. Similar β2-AR activation at day 5 postcoitus, when implantation sites have been established, did not affect embryo spacing or pregnancy outcome, indicating that the adverse effect of β2-AR activation is limited to the preimplantation period before embryo attachment. In vitro and in vivo studies demonstrated that the transient β2-AR activation abolished normal preimplantation uterine contractility without adversely affecting blastocyst quality. The contractility inhibition is mediated by activation of the cAMP-PKA pathway and accompanied by specific down-regulation of lpa3, a gene previously found to be critical for uterine contraction and embryo spacing. These results indicated that normal uterine contraction-mediated correct intrauterine embryo distribution is crucial for successful ongoing pregnancy. Abnormal β2-AR activation at early pregnancy provided a molecular clue in explaining how maternal stress at early stages could adversely affect the pregnancy outcome.

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Decidualization in the post-partum uterus of the mouse

Cited by 10 publications

References 10 publications

RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss

RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss

Matrix Metalloproteinases in Endometrial Breakdown and Repair: Functional Significance in a Mouse Model1

Transient β2-Adrenoceptor Activation Confers Pregnancy Loss by Disrupting Embryo Spacing at Implantation

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