Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition

Condon, Jennifer C.; Jeyasuria, Pancharatnam; Faust, Julie M.; Mendelson, Carole R.

doi:10.1073/pnas.0401124101

Cited by 321 publications

(296 citation statements)

References 53 publications

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“…According to the findings of an experimental study, SP-A in the amniotic fluid potentially regulates the duration of pregnancy, as implicated by the fact that its concentration levels increase strikingly as gestation proceeds toward term labor; moreover, a high concentration of SP-A was shown to induce proinflammatory cytokine expression in macrophages in vitro (25). However, in our study, the polymorphisms of SFTPA1 and SFTPA2 did not show any association with SPTB.…”

Section: Articlescontrasting

confidence: 55%

A study of collectin genes in spontaneous preterm birth reveals an association with a common surfactant protein D gene polymorphism

et al. 2011

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ArticlesClinical Investigation nature publishing group INTRODUCTION: Preterm birth is the major cause of mortality and morbidity in neonates. Intrauterine infection and/or inflammatory response are evident in 60-70% of spontaneous preterm births (sPTBs). Genetic factors significantly increase this risk. however, the genetic background associated with sPTB is poorly understood. surfactant protein (sP) a, sP-D, and mannose-binding lectin (MBL) are structurally and functionally related collectins that bind pathogen-associated molecular patterns, and mostly suppress innate immune responses. RESULTS:We detected an overrepresentation of the methionine allele of the SFTPD gene (encoding sP-D) Met31Thr polymorphism in preterm infants as compared to term infants. This association was highly significant in infants of families with recurrent sPTBs (P = 0.001, odds ratio = 1.65, 95% confidence interval = 1.22-2.22); however, there was no such association with SFTPD in the mothers of these infants. Polymorphism of the genes encoding sP-a and MBL did not influence the risk of sPTB. DISCUSSION: Our results suggest that the fetal SFTPD Met31Thr polymorphism plays a significant role in genetic predisposition to sPTB. We propose that fetal immune responses influence sensitivity to preterm labor-inducing signals. METHODS: Genes encoding sP-a, sP-D, and MBL were investigated as potential candidates for association with sPTB in a population of preterm singleton infants (n = 406) and their mothers (n = 308), and in mothers with term deliveries (n = 201) and their infants (n = 201), all originating from northern Finland.

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Section: Articlescontrasting

confidence: 55%

A study of collectin genes in spontaneous preterm birth reveals an association with a common surfactant protein D gene polymorphism

et al. 2011

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“…Based on investigations from our laboratory and others, we postulate that the timing of parturition is mediated by integrated signaling pathways from both the mother and maturing fetus (25). These culminate in an inflammatory response within the uterus and cervix, which leads to a reduction in PR function (2, 3), exacerbated inflammatory signaling, cervical ripening, and activation of contraction-associated genes within the myometrium.…”

Section: Discussionmentioning

confidence: 99%

miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor

Renthal

Chen²,

Williams

et al. 2010

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

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Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, whereas spontaneous labor is initiated/facilitated by a concerted series of biochemical events that activate inflammatory pathways and have a negative impact on PR function. In this study, we uncovered a previously undescribed regulatory pathway whereby micro-RNAs (miRNAs) serve as hormonally modulated and conserved mediators of contraction-associated genes in the pregnant uterus in the mouse and human. Using miRNA and gene expression microarray analyses of uterine tissues, we identified a conserved family of miRNAs, the miR-200 family, that is highly induced at term in both mice and humans as well as two coordinately downregulated targets, zinc finger E-box binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors. We also observed up-regulation of the miR-200 family and down-regulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly up-regulated by the action of progesterone (P 4 )/PR at the ZEB1 promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of the contractionassociated genes, oxytocin receptor and connexin-43, and block oxytocin-induced contractility in human myometrial cells. Together, these findings implicate the miR-200 family and their targets, ZEB1 and ZEB2, as unique P 4 /PR-mediated regulators of uterine quiescence and contractility during pregnancy and labor and shed light on the molecular mechanisms involved in preterm birth.A lthough premature labor is the leading cause of neonatal morbidity and mortality in developed countries, the signaling mechanisms that maintain uterine quiescence during pregnancy and promote increased uterine contractility leading to labor at term and preterm remain incompletely defined (1). In mammalian pregnancy, uterine quiescence is maintained by elevated circulating progesterone (P 4 ) acting via the progesterone receptor (PR). Conversely, parturition is associated with a decline in maternal circulating P 4 and/or a decrease in the function of the PR, termed "functional P 4 withdrawal," (2, 3) and an increased inflammatory response within the uterus and cervix (4). Studies from a number of laboratories, including our own, suggest that P 4 and PR maintain uterine quiescence until term by inhibiting expression of contraction-associated genes [e.g., connexin-43 (CXN-43), oxytocin receptor (OXTR), cyclooxygenase 2 (COX-2)] in the myometrium, in part, via anti-inflammatory actions. For example, P 4 and PR inhibit activation of COX-2 expression in myometrial cells through direct interaction of PR with NF-κB p65 (5) and by P 4 -induced expression of the NF-κB inhibitor, IκB-α (6).Recently, it has been shown that micro-RNAs (miRNAs) play especially powerful roles in vascular smooth muscle cells and in female reproduction, wherein they have been implicated in proliferation, differentiation, and hormone responsiveness (7-9). The identification o...

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“…The action of TNF-a on human decidua may be mediated by an autocrine or paracrine mechanism, where it is released by DMs on exposure to LPS and may induce stimulation of PGF 2a production by macrophages, thereby precipitating preterm labour (Norwitz et al 1992). Macrophages isolated from the amniotic fluid of pregnant mice respond to fetal surfactant protein A (SP-A) by increasing IL-1b and NF-kB production, and this may trigger uterine activation and labour (Condon et al 2004). SP-A levels increase sharply in human amniotic fluid towards term (Miyamura et al 1994) and it would be of interest to study its effect on human DMs.…”

Section: Discussionmentioning

confidence: 99%

Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

Singh¹,

Nicholson²,

Urban³

et al. 2005

Reproduction

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Our aim was to investigate the contribution of decidual macrophages, which constitute an important immune component of the decidua in late gestation, to intrauterine defence mechanisms. Using flow cytometry we examined the ability of decidual macrophages, isolated from term decidua, to bind and phagocytose fluorescence-labelled bacterial and yeast bioparticles. We also assessed their ability to generate superoxide radicals and tumour necrosis factor-a following lipopolysaccharide challenge. Decidual macrophages bound bacterial and yeast particles in a dose-dependent manner, which subsequently led to phagocytosis. These macrophages also produced superoxide radicals and the pro-inflammatory cytokine TNF-a when challenged with bacterial lipopolysaccharides. These results suggest a role for decidual macrophages in pathogen recognition and clearance during pregnancy, and, therefore, they are likely to protect the fetus against intrauterine infections which might otherwise lead to preterm labour.

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Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition

Cited by 321 publications

References 53 publications

A study of collectin genes in spontaneous preterm birth reveals an association with a common surfactant protein D gene polymorphism

A study of collectin genes in spontaneous preterm birth reveals an association with a common surfactant protein D gene polymorphism

miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor

Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

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