Preterm labor is a distinct process from term labor following computational analysis of human myometrium

Abstract

BACKGROUND:The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor. OBJECTIVE: This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures. STUDY DESIGN: Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n¼31), term labor (n¼13), preterm not in labor (n¼21), preterm labor with acute clinical chorioamnionitis (n¼6), preterm labor with no acute clinical chorioamnionitis (n¼9), twin preterm not in labor (n¼8), and twin preterm labor with no acute clinical chorioamnionitis (n¼5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis.RESULTS: Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term notin-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity. CONCLUSION: The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.

Assessing the Potency of the Novel Tocolytics 2-APB, Glycyl-H-1152, and HC-067047 in Pregnant Human Myometrium

“…Evidence suggests that PTL is a syndrome attributable to multiple pathological processes, including infection or inflammation, uterine overdistension, stress, ischemia or hemorrhage, endocrine disorders, immunologically mediated processes [ 55 ], and a gene expression pattern distinct from term labor [ 56 ]. Thus, PTL is a heterogeneous condition of multiple dysfunctions of preterm tissue that may lead to myometrial contractions, membrane/decidual activation, and/or cervical ripening.…”

“…Hence, it is unclear whether spontaneous PTL results from premature activation of the term labor process, or due to pathological insults initiating uterine transformation from quiescence to overt labor [ 57 ]. Although evidence indicates that preterm and term labor are distinct processes [ 56 ], the preterm and term labor ultimately converge at the level of the myometrial contractile proteins. In this regard, there are no data available reporting that the levels of contractile proteins relevant to this study (IP 3 R, TRPV4, L-type Ca 2+ channels, and ROCK) change between preterm and term human myometrium.…”

“…The study has only examined tocolytic potency against unstimulated (spontaneous) ex vivo contractions in term, NIL pregnant human myometrium. The authors acknowledge that there is increasing evidence that there are distinct differences between preterm and term labor [ 56 ], which may call into question the relevance of these data gleaned from term NIL myometrium. However, as previously mentioned, there are no data available indicating that levels of IP 3 R [ 99 – 101 ], TRPV4 [ 43 ], and ROCK [ 34 , 102 , 103 ] change between preterm and term pregnant human myometrium.…”

Different pathways for preterm birth between singleton and twin pregnancies: a population‐based registry study of 481 176 nulliparous women

“…Numerous maternal and fetal pregnancy‐related complications that may lead to preterm delivery, such as hypertensive disorders of pregnancy, congenital malformations and fetal demise, are more common in twin pregnancies than in singleton pregnancies 3,4 . Preterm birth is a complex syndrome, and the underlying mechanisms may differ between singleton and twin gestations 5–9 . The extent of obstetric complications leading to preterm birth in twin pregnancies compared with singleton pregnancies is not well understood and has not been extensively studied.…”

“… 3 , 4 Preterm birth is a complex syndrome, and the underlying mechanisms may differ between singleton and twin gestations. 5 , 6 , 7 , 8 , 9 The extent of obstetric complications leading to preterm birth in twin pregnancies compared with singleton pregnancies is not well understood and has not been extensively studied.…”