A role for menstruation in preconditioning the uterus for successful pregnancy

Brosens, Jan J.; Parker, Malcolm G.; McIndoe, Angus; Pijnenborg, Robert; Brosens, Ivo

doi:10.1016/j.ajog.2008.11.037

Cited by 136 publications

(98 citation statements)

References 51 publications

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“…Though a majority of studies of the pathogenesis of pre-eclampsia have focused on abnormal EVT function or survival, some authors have pointed to the likelihood that alterations in the uterine environment are important in pregnancy pathology. 54 We anticipate that these findings will open up new avenues for investigation to decipher the involvement of decidual immune cells in insufficient vascular remodeling and trophoblast invasion.…”

Section: Discussionmentioning

confidence: 95%

Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy

Smith

Dunk

Aplin

et al. 2009

The American Journal of Pathology

410

381

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Decidual artery remodeling is essential for a healthy pregnancy. This process involves loss of vascular smooth muscle cells and endothelium, which are replaced by endovascular trophoblasts (vEVTs) embedded in fibrinoid. Remodeling is impaired during preeclampsia, a disease of pregnancy that results in maternal and fetal mortality and morbidity. Early vascular changes occur in the absence of vEVTs, suggesting that another cell type is involved; evidence from animal models indicates that decidual leukocytes play a role. We hypothesized that leukocytes participate in remodeling through the triggering of apoptosis or extracellular matrix degradation. Decidua basalis samples (8 to 12 weeks gestation) were examined by immunohistochemistry to elucidate associations between leukocytes, vEVTs, and key remodeling events. Trophoblast-independent and -dependent phases of remodeling were identified. Based on a combination of morphological attributes, vessel profiles were classified into a putative temporal series of four stages. In early stages of remodeling, vascular smooth muscle cells showed dramatic disruption and disorganization before vEVT presence. Leukocytes (identified as uterine natural killer cells and macrophages) were apparent infiltrating vascular smooth muscle cells layers and were matrix metalloproteinase-7 and -9 immunopositive. A proportion of vascular smooth muscle cells and endothelial cells were terminal deoxynucleotidyl transferase dUTP nick-end labeling positive, suggesting remodeling involves apoptosis. We thus confirm that vascular remodeling occurs in distinct trophoblast-independent and -dependent stages and provide the first evidence of decidual leukocyte involvement in trophoblastindependent stages.

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Section: Discussionmentioning

confidence: 95%

Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy

Smith

Dunk

Aplin

et al. 2009

The American Journal of Pathology

410

381

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“…Third, it is important to realise that the uterus cannot be viewed as an organ a priori designed to carry a pregnancy to term. For example, it is increasingly apparent that cyclic waves of spontaneous decidualisation, menstruation and endometrial regeneration play an important role in embryo selection at implantation and in the preconditioning of the vasculature prior to deep trophoblast invasion [46].…”

Section: Challenges To Uterine Functions In Pregnancy After Human Utementioning

confidence: 99%

The risk of obstetrical syndromes after solid organ transplantation

Brosens

Benagiano

2014

Best Practice & Research Clinical Obstetrics & Gynaecol

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“…These studies focused on the functionalis response to ovarian steroids, its receptivity to blastocyst implantation, and the development of endometriosis and endometrial cancer, but none addressed the differences between functionalis and basalis. Moreover, menstruation was rarely investigated (10) despite its increasingly recognized importance (11). Analysis of total tissue extracts obscures local regulatory networks between glands and stromal cells that trigger degradation and repair of the functionalis while preserving the basalis.…”

mentioning

confidence: 99%

Spatiotemporal Coupling of Focal Extracellular Matrix Degradation and Reconstruction in the Menstrual Human Endometrium

et al. 2009

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Coupling of focal degradation and renewal of the functional layer of menstrual endometrium is a key event of the female reproductive biology. The precise mechanisms by which the various endometrial cell populations control extracellular matrix (ECM) degradation in the functionalis while preserving the basalis and the respective contribution of basalis and functionalis in endometrium regeneration are still unclear. We therefore compared the transcriptome of stromal and glandular cells isolated by laser capture microdissection from the basalis as well as degraded and preserved areas of the functionalis in menstrual endometria. Data were validated by in situ hybridization. Expression profile of selected genes was further analyzed throughout the menstrual cycle, and their response to ovarian steroids withdrawal was studied in a mouse xenograft model. Immunohistochemistry confirmed the results at the protein level. Algorithms for sample clustering segregated biological samples according to cell type and tissue depth, indicating distinct gene expression profiles. Pairwise comparisons identified the greatest numbers of differentially expressed genes in the lysed functionalis when compared with the basalis. Strikingly, in addition to genes products associated with tissue degradation (matrix metalloproteinase and plasmin systems) and apoptosis, superficial lysed stroma was enriched in gene products associated with ECM biosynthesis (collagens and their processing enzymes). These results support the hypothesis that fragments of the functionalis participate in endometrial regeneration during late menstruation. Moreover, menstrual reflux of lysed fragments overexpressing ECM components and adhesion molecules could easily facilitate implantation of endometriotic lesions.

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A role for menstruation in preconditioning the uterus for successful pregnancy

Cited by 136 publications

References 51 publications

Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy

Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy

The risk of obstetrical syndromes after solid organ transplantation

Spatiotemporal Coupling of Focal Extracellular Matrix Degradation and Reconstruction in the Menstrual Human Endometrium

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