MMP‐2 expression precedes the final ripening process of the bovine cervix

Engelen, E. van; Breeveld-Dwarkasing, V.N.A.; Taverne, M.A.M.; Everts, M. E.; Weijden, G.C. van der; Rutten, Victor P.M.G.

doi:10.1002/mrd.20908

Cited by 18 publications

(14 citation statements)

References 41 publications

(62 reference statements)

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“…370 Increases in MMP-2 expression/activity have also been observed in the final ripening stages and collagen denaturation of the cervix during late pregnancy. 371 MMP-2 and MMP-9 have also been detected in the bovine endometrium and myometrium during pregnancy. 28,103,366 We have shown an upregulation of MMP-2 and MMP-9 in the myometrium of late pregnant rats, and suggested a role of MMPs in pregnancy-related uterine remodeling.…”

Section: Mmps and Uterine Contraction During Pregnancy And Labormentioning

confidence: 97%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

228

168

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Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy. MMP expression/activity may be altered during complications of pregnancy. Decreased vascular MMP-2 and MMP-9 may lead to decreased vasodilation, increased vasoconstriction, hypertensive pregnancy and preeclampsia. Abnormal expression of uteroplacental integrins, cytokines and MMPs may lead to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate remodeling of spiral arteries, and reduced uterine perfusion pressure (RUPP). RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, or stimulate the release of inflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could target MMPs in the extracellular matrix as well as endothelial and vascular smooth muscle cells, causing generalized vascular dysfunction, increased vasoconstriction and hypertension in pregnancy. MMP activity can also be altered by endogenous tissue inhibitors of metalloproteinases (TIMPs) and changes in the MMP/TIMP ratio. In addition to their vascular effects, decreases in expression/activity of MMP-2 and MMP-9 in the uterus could impede uterine growth and expansion and lead to premature labor. Understanding the role of MMPs in uteroplacental and vascular remodeling and function could help design new approaches for prediction and management of preeclampsia and premature labor.

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Section: Mmps and Uterine Contraction During Pregnancy And Labormentioning

confidence: 97%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

228

168

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“…Premature shortening of the cervix is the strongest clinical predictor of premature birth 10 . It is also critically important for making term delivery possible in humans 10 , mice 8 , sheep 12 , cow 13, 14 . How cervical remodeling is regulated is one of the major unanswered questions in female reproductive biology and critical for research on the prevention of prematurity 15 .…”

Section: Introductionmentioning

confidence: 99%

Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical ripening

Wagner

Nnamani

Chavan

et al. 2017

Sci Rep

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The uterine cervix is the boundary structure between the uterus and the vagina and is key for the maintenance of pregnancy and timing of parturition. Here we report on a comparative transcriptomic study of the cervix of four placental mammals, mouse, guinea pig, rabbit and armadillo, and one marsupial, opossum. Our aim is to investigate the evolution of cervical gene expression as related to putative mechanisms for functional progesterone withdrawal. Our findings are: 1) The patterns of gene expression in eutherian (placental) mammals are consistent with the notion that an increase in the E/P4 signaling ratio is critical for cervical ripening. How the increased E/P4 ratio is achieved, however, is variable between species. 2) None of the genes related to steroid signaling, that are modulated in eutherian species, change expression during opossum gestation. 3) A tendency for decreased expression of progesterone receptor co-activators (NCOA1, -2 and -3, and CREBBP) towards term is a shared derived feature of eutherians. This suggests that parturition is associated with broad scale histone de-acetylation. Western-blotting on mouse cervix confirmed large scale histone de-acetylation in labor. This finding may have important implications for the control of premature cervical ripening and prevention of preterm birth in humans.

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“…2003b), expression of inducible nitric oxide synthase (iNOS; Aalberts et al. 2007), matrix metallo‐proteinases (MMP’s; Van Engelen et al. 2008a) and several cytokines (Van Engelen et al.…”

Section: Introductionmentioning

confidence: 99%

Parturition in Domestic Animals: Targets for Future Research

Taverne

Weijden

2008

Reprod Domestic Animals

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Contents Compared with other parts of the reproductive cycle, the parturition process of domestic animals has received relatively little attention from researchers during the last two decades. Yet, interventions during parturition, either by the owner or the veterinarian, are frequently judged necessary and perinatal losses in most of the domestic species are (still) rather high. The present paper focuses on the birth process in three domestic species, the dog, pig and cow, mainly because most of the experimental and research work of the authors themselves was dealing with these three species. Against the background of specific clinical problems, breeding circumstances and economic performance, selected topics and questions are addressed to identify areas for future research. These are, among others, related to the mechanisms that trigger the birth process (are the foetuses involved in the dog and sow?), the role of hormones and cytokines during ripening of the cervix (activation and/or de-activation of specific matrix metallo-proteinases and their local inhibitors), the functional significance of fetal body movements to prepare the foetus for expulsion, and the exact time course of events involved in the transportation of an individual foetus from its intrauterine location, via the pelvic canal, to the outside world. Research on some of these topics, such as the ripening of the cervix in cows, might also contribute to resolve clinical problems in human obstetrics.

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MMP‐2 expression precedes the final ripening process of the bovine cervix

Cited by 18 publications

References 41 publications

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical ripening

Parturition in Domestic Animals: Targets for Future Research

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