**2.4. Placenta microRNAs in pregnancy**

**2.3. Term labor and gene expression**

32 Placenta

**Species Placenta and** 

Human 5–10 min before

Human Preterm

Human Term (38–

Human Term (34 weeks) with vaginal (laboring) delivery or cesarean (non-laboring)

Human Term and term nonlaboring cesarean deliveries

**gestational age**

delivery (preterm labor or not)

(26–36 weeks) Term (>37 weeks) all with suspicion of preterm labor

42 weeks) with vaginal delivery or cesarean

The molecular mechanisms regulating the initiation of labor are still poorly understood. The key role of genes involved in prostaglandin synthesis and inflammatory responses in cervix, myometrium and chorio-membranes has been reported in laboring women as compared with non-laboring women [24]. **Table 3** summarized the studies evaluating placenta gene expression from preterm versus term labor with vaginal or cesarean deliveries. The commonly modulated genes are involved in immune response and apoptosis. Oros et al. showed a balance of immune modulators with an increased expression of tumor necrosis factor (TNF) and interleukin (IL)-6 and a decrease in interferon (IFN)-γ expression [26]. These results are likely related with cytokine production of at term placentas [30] and M1 polarization shift of macrophages [31]. Another study showed that gene expression associated with oxidative stress is elevated [25]. It has been previously observed that oxidative stress in placenta explants

**Technique Results References**

cell surface receptor-linked signal transduction, regulation of transcription, immune system process, blood vessel development, death, cell-adhesion, cell-cell signaling, coagulation and oxygen and reactive oxygen species metabolism

• Decreased expression of IFN-γ and VEGFR1 • Term delivery after suspicion of preterm labor

• Preterm delivery after suspicion of preterm labor

involved in angiogenic regulators, immune response, inflammatory response and apoptosis

laboring placentas compared to no-laboring

• FOS, FOSb and GNGT1 are down-modulated in laboring placentas compared to non-laboring

homeostasis are up-modulated such as fibronectin

[25]

[26]

[27]

[28]

[29]

Microarray • Functional ontology analysis response to stress,

qRT-PCR • Increased expression of TNF, IL-6 and PGF

shows decreased VEGFA

shows decreased VEGFB

Microarray • Up-regulated genes in placenta by labor are

Microarray • 92 genes down- and 94 up-regulated genes in

Microarray • Labor is associated with up-modulated expression of MMP-1 gene in chorionic villus tissue • Genes involved in the extracellular matrix

placentas

placentas

**Table 3.** Transcriptomic analysis of uncomplicated pregnancies from preterm or term labor.

1 and collagen XVII

process

MicroRNAs are small non-coding 20–24 nucleotides that target and regulate numerous genes [35]. They are expressed by tissues and cells but can also circulate in blood. They can be used as biomarkers [36]. It has been reported that more than 500 microRNAs are produced by the human placenta and a part of them are placenta specific [37]. Their expression varies with the gestational stages; 191 microRNAs are differentially modulated in placentas from first versus third trimester [38]. During the first trimester, microRNAs are associated with angiogenesis, anti-apoptosis and oncogenesis categories, whereas microRNAs from third trimester are related to cell differentiation and tumor suppression categories. Luo et al. found that miR-378a-5p is up-modulated in first and second trimesters but not in third trimester in placenta tissue [39]. The variations of microRNAs expression during different gestational ages suggest that they may regulate specific functions during pregnancy. However, the studies investigating microRNAs in total tissue in normal pregnancy are scarce and further investigations are necessary to better characterize microRNA signature and their temporal expression pattern in the placenta at different ages of gestation.
