The expression of miRNA encoded by C19MC and miR-371-3 strongly varies among individual placentas but does not differ between spontaneous and induced abortions

Abstract

miRNAs of the largest human miRNA gene cluster at all, i.e., C19MC, are almost exclusively expressed in the placenta. Nevertheless, only little is known about the interindividual variation of their expression and even about possible influence of gestational age, conflicting data is reported as well as for miRNAs of the much smaller miR-371-3 cluster. Our present study aims at the analyses of the expression of miRNAs from both clusters at different times of pregnancy, possible differences between placenta samples obtained from spontaneous or induced abortions in the first trimester, and the possible variation of miRNA expression at different sites within same placentas. miR-371a-3p, miR-372-3p, miR-373-3p, miR-517a-3p, and miR-520c-3p were quantified in 85 samples and miR-371a-3p was quantified in maternal serum samples taken immediately before delivery. While for miRNA-517a-3p and miR-520c-3p the expression increased with increasing gestational age, the present study revealed strong interindividual differences in the expression of miR-371-3 in full-term placental tissue as well as for miRNAs of the C19MC cluster, where the levels differed to a much lesser extent than for the former microRNAs. Also, strong interindividual differences were noted between the serum samples but differences related to the site of the placenta where the sample has been taken from were excluded. For neither of the data from placental tissue, the study revealed differences between the spontaneous and induced abortion group. Thus, the differences do not in general seem to be related to first trimester abortion. It remains to be elucidated whether or not they affect other prenatal processes.

The role of miRNA molecules in the miscarriage process

“…There was a 20-fold increase in miR-517a , which partly coincided with the study by Gottlieb et al [55, 121]. Furthermore, Wang et al showed elevated expression of miR-517a-3p in the decidual tissue and chorion of the trophoblast in women with multiple miscarriages, which was similar to the results by Gottlieb et al [55, 122].…”

“…C19MC miRNAs are among the most highly expressed miRNAs in the human placenta and the serum of pregnant women [114, 115]. The study by Gottlieb et al investigated if the occurrence of miscarriage is affected by miR-371-3 cluster, which crosses the maternal–fetal barrier [55]. Unfortunately, there was no confirmation of this hypothesis, and significant differences in the expression of any of the miRNA molecules tested, including miR-371-3 cluster, could not be obtained.…”

“…Furthermore, whether miR-371-3 cluster and C19MC affect other fundamental processes in prenatal life was also not clarified. The miR-371-3 cluster was singled out for its involvement in stem cell formation and maintenance and cell differentiation, which likely plays a role in trophoblast differentiation [55, 118, 119]. However, in their study, Gu et al observed a decrease in the levels of miR-371-3 and miR-520c in the placental tissue, mainly during the third trimester of pregnancy [120].…”

“…Gottlieb et al., in their study, analyzed placental tissues from women with miscarriage to evaluate the C19MC cluster (Chromosome 19 microRNA cluster) and five miRNA molecules: miR-373-3p (lowest expression), miR-371a-3p , miR-372-3p , miR-520c-3p , and miR-517a-3p (highest expression) [ 55 , 114 ]. The C19MC is a microRNA cluster consisting of 46 genes, which in turn encodes 59 mature miRNAs [ 115 , 116 ].…”

Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia

“…In primary trophoblasts isolated from normal term placentas, 41 out of the 46 C19MC miRNA genes were expressed and they represented the majority of miRNAs expressed in these cells as well as in the exosomes secreted by them ( Luo et al, 2009 ; Donker et al, 2012 ; Lee et al, 2016 ). Temporally, studies have shown that C19MC miRNAs exhibit a dynamic gestational expression profile ( Gottlieb et al, 2021 ); however, there are inconsistencies among different reports. One study showed that 46 mature C19MC miRNAs were higher in third trimester villous trophoblasts compared to first trimester cells ( Donker et al, 2012 ; Morales-Prieto et al, 2012 ), while another study showed that the expression of some C19MC members were higher in first trimester samples (ranged 6–10 weeks) than in second trimester ones (ranged 11–23 weeks) ( Smith et al, 2021 ).…”