Preterm labor: One syndrome, many causes

Romero, Roberto; Dey, Sudhansu K.; Fisher, Susan J.

doi:10.1126/science.1251816

Cited by 1,511 publications

(1,403 citation statements)

References 71 publications

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“…Breakdown in immune tolerance has been linked to rejection, which in pregnancy can have variable consequences depending on the gestation: recurrent miscarriages (Kuon et al 2015), PTL (Romero et al 2014a) and pre-eclampsia (Dietl 2000). Tolerance is maintained via factors produced at the implantation site, one such promoter of tolerance is IL-10, an anti-inflammatory cytokine (Thaxton & Sharma 2010).…”

Section: :3mentioning

confidence: 99%

“…Haemorrhage Decidual haemorrhage is associated with PTL (Romero et al 2014a) and it complicates 0.5-2% of all pregnancies (Buhimschi et al 2010). Decidual haemorrhage was generally accepted as an acute event; however, histological evaluation of the vasculopathy accompanying decidual haemorrhage provides compelling evidence that the damage is frequently chronic (Salafia et al 1995, Elsasser et al 2010.…”

Section: Figurementioning

confidence: 99%

“…These microorganisms and their products are typically identified by pattern recognition receptors such as toll-like receptors, which induce the production of chemokines (IL-8, IL-1, CCL-2) and cytokines (IL-1β, TNF-α) (Romero et al 2014a). With regard to periodontitis pathogens it is likely that their effect is triggered by translocation of bacterial products, such as LPS, which can trigger common parturition pathway via inflammatory mediators such as IL-6 and TNF-α (Parthiban 2015).…”

Section: Pathologymentioning

confidence: 99%

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Myometrial cytokines and their role in the onset of labour

Sivarajasingam

Imami

Johnson

2016

Journal of Endocrinology

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Human labour is an inflammatory event, physiologically driven by an interaction between hormonal and mechanical factors and pathologically associated with infection, bleeding and excessive uterine stretch. The initiation and communicators of inflammation is still not completely understood; however, a key role for cytokines has been implicated. We summarise the current understanding of the nature and role of cytokines, chemokines and hormones and their involvement in signalling within the myometrium particularly during labour.

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Section: :3mentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Pathologymentioning

confidence: 99%

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Myometrial cytokines and their role in the onset of labour

Sivarajasingam

Imami

Johnson

2016

Journal of Endocrinology

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“…Approximately 25% of preterm births are associated with occult microbial invasion of the amniotic cavity (5). Evidence suggests that the most common source of invading microbes is the host microbiota.…”

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confidence: 99%

Temporal and spatial variation of the human microbiota during pregnancy

DiGiulio

Callahan

McMurdie

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

895

966

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Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/ gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.16S rRNA gene | pregnancy | preterm birth | microbiome | premature labor

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“…Inflammation is an important component of the parturition process in eutherian mammals, and infection can cause preterm labor (68,69). In wallabies, inflammatory prostaglandins are sufficient to induce parturition behavior, and blocking prostaglandin activity late in gestation results in the extension of pregnancy (70,71).…”

Section: Evolution and Function Of The Attachment Reaction During Thementioning

confidence: 99%

Embryo implantation evolved from an ancestral inflammatory attachment reaction

Griffith

Chavan

Protopapas

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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177

141

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The molecular changes that support implantation in eutherian mammals are necessary to establish pregnancy. In marsupials, pregnancy is relatively short, and although a placenta does form, it is present for only a few days before parturition. However, morphological changes in the uterus of marsupials at term mimic those that occur during implantation in humans and mice. We investigated the molecular similarity between term pregnancy in the marsupials and implantation in eutherian mammals using the gray short-tailed opossum (Monodelphis domestica) as a model. Transcriptomic analysis shows that term pregnancy in the opossum is characterized by an inflammatory response consistent with implantation in humans and mice. This immune response is temporally correlated with the loss of the eggshell, and we used immunohistochemistry to report that this reaction occurs at the materno-fetal interface. We demonstrate that key markers of implantation, including Heparin binding EGF-like growth factor and Mucin 1, exhibit expression and localization profiles consistent with the pattern observed during implantation in eutherian mammals. Finally, we show that there are transcriptome-wide similarities between the opossum attachment reaction and implantation in rabbits and humans. Our data suggest that the implantation reaction that occurs in eutherians is derived from an attachment reaction in the ancestral therian mammal which, in the opossum, leads directly to parturition. Finally, we argue that the ability to shift from an inflammatory attachment reaction to a noninflammatory period of pregnancy was a key innovation in eutherian mammals that allowed an extended period of intimate placentation.placenta | marsupial | inflammation | pregnancy | evolution I n eutherian (so-called "placental") mammals, pregnancy begins when the blastocyst attaches to the uterine wall, followed by the establishment of a stable fetal-maternal interface. Implantation involves the apposition, attachment, and, in many species, the invasion of the blastocyst into the uterus (1). In particular, structural and molecular changes occur in the luminal epithelia that allow the embryo to attach and invade the uterus (2). Epithelial changes are followed by remodeling of the endometrial stroma, generally known as "decidualization," i.e., the transformation of endometrial stromal fibroblasts into decidual stromal cells, as well as modifications of the endometrial vascular bed (3). When these changes do not occur or occur incompletely, blastocysts fail to implant, resulting in early pregnancy failure (4, 5). In humans, 75% of unsuccessful pregnancies are the result of failures of implantation, and implantation failure is the limiting factor for in vitro fertilization treatment. Furthermore, decades of research have failed to produce clinically effective treatments that increase uterine receptivity to implantation (6-8). Given the magnitude of this problem, extensive efforts have been made to characterize the endometrium for signatures of receptivity (9, 10).Implantati...

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Preterm labor: One syndrome, many causes

Cited by 1,511 publications

References 71 publications

Myometrial cytokines and their role in the onset of labour

Myometrial cytokines and their role in the onset of labour

Temporal and spatial variation of the human microbiota during pregnancy

Embryo implantation evolved from an ancestral inflammatory attachment reaction

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