Steroid hormone control of myometrial contractility and parturition

Mesiano, Sam; Welsh, Toni

doi:10.1016/j.semcdb.2007.05.003

Cited by 122 publications

(90 citation statements)

References 105 publications

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“…Several studies demonstrated that progesterone promotes myometrial relaxation. [43][44][45] Our finding that the absence of C5aR prevents PTD in the mouse models has important therapeutic implications. Blocking the complement cascade at C5a and CaR interaction inhibits mediators and effectors of cervical remodeling and prevents PTD, suggesting that complement might be a good target for therapy in women with PTD.…”

Section: Discussionmentioning

confidence: 90%

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

González

Franzke

Yang

et al. 2011

The American Journal of Pathology

157

177

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Inflammation is frequently linked to preterm delivery (PTD). Here, we tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS) and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophages infiltration and increased serum C3adesArg and C5adesArg levels were observed in both models when compared to gestational age matched controls. A significant increase in collagen degradation, matrix metalloproteinase 9 (MMP-9) activity and tissue distensibility was observed in the cervix in both models. Mice deficient in complement receptor C5a did not show increased MMP-9 activity and cervical remodeling and did not deliver preterm in response to LPS or RU486, suggesting a role for C5aR in the cervical changes that precede PTD. In vitro studies show that macrophages release MMP-9 in response to C5a. Progesterone diminished the amount of C5aR on the macrophages surface, inhibited the release of MMP-9 and prevented PTD. In addition, macrophages depletion also prevented cervical remodeling and PTD in LPS-treated mice. Our studies show that C5a-C5aR interaction is required for MMP-9 release from macrophages, and the cervical remodeling that leads to PTD. Complement inhibition and supplementation with progesterone may be good therapeutic options to prevent this serious pregnancy complication. Premature birth/delivery (PTD) is one of the most significant causes of perinatal mortality and morbidity in developed countries. Preterm infants suffer morbidities including respiratory distress, intraventricular hemorrhage, and cerebral palsy, among other serious diseases.1 These outcomes can have a life-long impact and more than $25 billion is spent each year to take care of these infants. Investigations to define the causes of PTD remain a challenge in the obstetrical field. Preterm labor is a multistage biochemical and biophysical process, during which changes in the myometrium and the cervix occur.The uterine cervix is a complex organ that undergoes extensive changes through gestation and parturition. These changes are a common first step in preterm parturition.2 As a gatekeeper for pregnancy, the cervix is a structural barrier that keeps the fetus inside the uterus until the end of gestation. Collagens, elastin, proteoglycans, and hyaluronate are responsible for the full tensile strength of the cervix.2 Ripening of the cervix is an important biological and clinical event required for a normal parturition. The process is gradual during pregnancy, with a fast final remodeling of the cervix before parturition. Increased collagen degradation and synthesis, and high activity of collagenases have been observed in the human cervix during final ripening.

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Section: Discussionmentioning

confidence: 90%

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

González

Franzke

Yang

et al. 2011

The American Journal of Pathology

157

177

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“…The observed decrease in fEM and fPM concentrations towards end of pregnancy, during week 18-19, should reflect the change in status of the foetal-maternal interface, which consequently initialises parturition (Audus et al 2002;Mesiano et al 2002;Mesiano and Welsh 2007). The average pregnancy length of 128 days determined is comparable to the 121 and 133 days described by Doyle et al (1971) and Lipschitz (1996), using observational data and the presence of spermatozoa in vaginal smears, but far less than the 141 days mentioned in studies using external parameters for determining pregnancy length (reviewed in Nekaris and Bearder 2007), indicating that using only behavioural or physical cues might result in inaccurate determination of pregnancy length for G. moholi.…”

Section: Discussionmentioning

confidence: 98%

Female reproductive activity and its endocrine correlates in the African lesser bushbaby, Galago moholi

et al. 2015

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Steroid hormones play an important role in female reproductive physiology and behaviour and are often used to monitor important female reproductive events. However, such studies are often attempted on captive populations alone, delivering limited data. One such example is the African lesser bushbaby, Galago moholi, for which contradicting observational data exist between captive and free-ranging populations, while hormonal analyses have only been obtained from a single captive population. To extend and rectify the limited information, we monitored faecal progestagen and oestrogen metabolite levels across various important life history stages of both captive and free-ranging G. moholi. We additionally recorded changes 2 in vaginal state as well as the occurrence of reproductive and aggressive behaviour throughout the study. Data from our captive population revealed an ovarian cycle length of 33.44 ± 0.59 days (mean ± SD), with follicular and luteal phases of 14.2 ± 1.0 and 19.1 ± 1.5 days, respectively, and an average pregnancy length of 128 ± 3.3 days. The initiation of female reproductive activity was closely linked to an oestrus-related increase in faecal oestrogen metabolite levels. Four of the seven captive females monitored in our study conceived during the May mating period, with one additional female fertilised in September, supporting the idea that the September mating period functions as a back-up for female G. moholi. Identified benchmark faecal progestagen metabolite levels (non-pregnant: > 1 µg/g dry weight (DW), pregnant: > 9 µg/g DW) should help researchers to determine pregnancy-status of randomly wild-caught females in even a cross-sectional study set-up.

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“…In mice, the gestation length is about 20 d when counted from the day of vaginal plug formation (day 1). The main biological events occurred within the uteri are embryo implantation, decidualization, placentation and labor [19][20][21], which mainly under the influence of ovarian progesterone and estrogen [22]. A preovulatory estrogen surge induces remarkable proliferation of uterine epithelial cells on day 1 [23,24], while rising levels of progesterone together with preimplantation estrogen secreted on the morning of day 4 induce stromal cell proliferation to establish an optimal milieu for blastocyst attach-ment to the uterine lining [25].…”

Section: Uterine Physiological Role In Normal Reproductive Eventsmentioning

confidence: 99%

Determinants of uterine aging: lessons from rodent models

Kong

Zhang

Chen

et al. 2012

Sci. China Life Sci.

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The uterus is an indispensable organ for the development of a new life in eutherian mammals. The female mammalian reproductive capacity diminishes with age. In this respect, the senescence of uterine endometrium is convinced to contribute to this failure. This review focuses on the physiological function of the uterus and the related influence of aging mainly in rodent models. A better understanding of the underlying mechanisms governing the process of uterine aging is hoped to generate new strategies to prolong the reproductive lifespan in humans. . More importantly, this phenomenon of continuous decline of fecundity with age has also been confirmed in women over 35 years old [10][11][12]. The success of reproduction in eutherian mammals requires the uterus, a unique organ in the viviparity compared to other organisms ensuring full development of the new life in the maternal body [13]. The endometrial environment of uteri is proved to be one of the critical aspects to determine the reproductive capacity [14] and uterine factor has been proved to be critical for the decline of fecundity in both rodents and humans [4,15]. Most of the available information on uterine aging derives from studies on rats and mice [16]. In these species, life span is short and aging animal model can be easily established. This review focuses on the physiological function of the uterus and the related influence of aging mainly in rodent models. determinants, uterine aging, rodent models

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Steroid hormone control of myometrial contractility and parturition

Cited by 122 publications

References 105 publications

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

Female reproductive activity and its endocrine correlates in the African lesser bushbaby, Galago moholi

Determinants of uterine aging: lessons from rodent models

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