Transcriptome interrogation of human myometrium identifies differentially expressed sense-antisense pairs of protein-coding and long non-coding RNA genes in spontaneous labor at term

Romero, Roberto; Tarca, Adi L.; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Jia, Hui; Hassan, Sonia S.; Kalita, Cynthia A; Cai, Juan; Yeo, Lami; Lipovich, Leonard

doi:10.3109/14767058.2013.860963

Cited by 23 publications

(12 citation statements)

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“…This is consistent with the idea that baseline inflammation can blunt responses to stimuli (61). In fact, this could be entirely consistent with the inflammatory signatures identified in earlier studies (5,(17)(18)(19)(20)(21)(22)(23)(24), all of which were performed in the absence of an exogenous stimulus.…”

Section: Discussionsupporting

confidence: 91%

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Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

et al. 2020

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Specific causes of preterm birth remain unclear. Several recent studies have suggested that immune changes during pregnancy are associated with the timing of delivery, yet few studies have been performed in low-income country settings where the rates of preterm birth are the highest. We conducted a retrospective nested case-control evaluation within a longitudinal study among HIV-uninfected pregnant Kenyan women. To characterize immune function in these women, we evaluated unstimulated and stimulated peripheral blood mononuclear cells in vitro with the A/California/2009 strain of influenza to understand the influenza-induced immune response. We then evaluated transcript expression profiles using the Affymetrix Human GeneChip Transcriptome Array 2.0. Transcriptional profiles of sufficient quality for analysis were obtained from 54 women; 19 of these women delivered <34 weeks and were defined as preterm cases and 35 controls delivered >37 weeks. The median time to birth from sample collection was 13 weeks. No transcripts were significantly associated with preterm birth in a case-control study of matched term and preterm birth (n = 42 women). In the influenza-stimulated samples, expression of IFNL1 was associated with longer time to delivery-the amount of time between sample collection and delivery (n = 54 women). A qPCR analysis confirmed that influenza-induced IFNL expression was associated with longer time to delivery. These data indicate that during pregnancy, ex vivo influenza stimulation results in altered transcriptional response and is associated with time to delivery in cohort of women residing in an area with high preterm birth prevalence.

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Section: Discussionsupporting

confidence: 91%

“…Transcriptomic evaluation of the uterus and fundus during labor in term and preterm birth have identified inflammatory signatures associated with labor and preterm birth (19)(20)(21)(22). Several additional studies have identified transcriptional signatures of inflammation in the placentas of women who undergo preterm delivery (23,24).…”

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confidence: 99%

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

et al. 2020

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“…Changes to the transcriptome of human myometrium have been demonstrated at the time of spontaneous labor, signaling a specific environment different from non-laboring myometrium. 20 Our use of wild-type mice to assess uterine contractility minimized any genetic variation that may have affected human myometrial contractility in our exploratory study. The variability in estrous phase of the mice at the time of contractility testing is a potential confounder.…”

Section: Resultsmentioning

confidence: 99%

Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model

et al. 2015

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We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2a-hydroxyprogesterone, 6b-hydroxyprogesterone (6b-OHP), 16a-hydroxyprogesterone (16a-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10 À9 to 10 À6 mol/L. Uterine horns were exposed to progestins (10 À6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocininduced contractile frequency was decreased by 16a-OHP (P ¼ .03) and increased by 6b-OHP (P ¼ .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P ¼ .02 and P ¼ .04, respectively) and frequency (P ¼ .02 and P ¼ .03, respectively). Only progesterone decreased spontaneous contractile force (P ¼ .02). Production of 16a-OHP and 6b-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility.

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“…Despite its frequency and importance, there are major gaps in knowledge about the diagnosis, pathogenesis, microbiology, maternal and fetal immune response, and short-and-long term consequences of clinical chorioamnionitis, as well as optimal treatment. Systems biology can help us make major gains in the understanding of this important condition [211–228]. …”

Section: Discussionmentioning

confidence: 99%

Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques

Romero¹,

Miranda²,

Kusanovic³

et al. 2015

Journal of Perinatal Medicine

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209

216

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Introduction The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection. Methods The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration ≥ 2.6ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations. Results 1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive formicroorganisms in 59% (27/46) – combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2) Ureaplasma urealyticum (n = 8) and Gardnerella vaginalis (n = 10) were the microorganisms most frequently identified by cultivation and PCR/ESI-MS, respectively. 3) When combining the results of AF culture, PCR/ESI-MS and AF IL-6 concentrations, 15% (7/46) of patients did not have intra-amniotic inflammation or infection, 6.5% (3/46) had only MIAC, 54% (25/46) had microbial-associated intra-amniotic inflammation, and 24% (11/46) had intra-amniotic inflammation without detectable microorganisms. 4) Placental lesions consistent with acute AF infection were significantly more frequent in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [70.8% (17/24) vs. 28.6% (2/7); P = 0.04]. Conclusion Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.

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Transcriptome interrogation of human myometrium identifies differentially expressed sense-antisense pairs of protein-coding and long non-coding RNA genes in spontaneous labor at term

Cited by 23 publications

References 173 publications

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model

Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques

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