ERRγ1 Might Regulate Aromatase mRNA Variant Expression in Human Placental Tissues from Term Deliveries of Large for Gestational Age (LGA) Newborns Deliveries

MARCOS PALLIGAS, BIOCHEMIST, CRISTINA NEMER, MD, CLAUDIA CANNIZZARO, MD, MARIA BAQUEDANO, BSC, PHD, ALICIA BELGOROSKY, MD, PHD ; NORA SARACO

Congreso; ENDO 2019; 2019

Estrogens play important role in the placenta throughout the gestation. Human placenta (PL) expresses high levels of ERRγ type 1 isoform as well as Aromatase (Aro).ERRγ1has also be described as possibly implicated in the regulation of theenergy metabolism in PL, however its physiological role is not yet clear.Aro is the key enzyme for estrogen biosynthesis from androgens and in human placenta is expressed exclusively in syncytiotrophoblast. It has been described that ERRγ serves as an oxygen-responsive transcription factor that regulates Aro gene expression in PL.We have previously described splicing variants of AromRNA(1-2). Our aim was to analyze ERRγ1 mRNA expression and Aro mRNA active variant expression in PL from term LGA and preterm (PT) (<35 weeks) compared to term adequate for gestational age (AGA) newborns. We propose that ERRγ1 expression in PL is involved in aromatase activity regulation and hence intrauterine estrogen-androgen balance. Total RNA was isolated from PL of PT (GA: 30-35 weeks,n=4), LGA (GA: 39-41 w,n=8) and two subgroups of AGA: AGA1 (GA: 37-38 w,n=8) and AGA2 (39-40 w, n=10). ERRγ1 mRNA and Aro mRNA variants were analyzed by Real-time RT-PCR with primers for total (TotAro, Ex2-Ex3), and active (ActAro, Ex9-Ex10)Aro. Cyclophilin (PPIA) was used as housekeeping gene. Statistics (Student test) were performed on ΔCt data. ERRγ1 mRNA was higher in LGA vs AGA2 (GA:39-40w), 8.66 ± 2.57 vs 2.84 ± 0.61 AU,mean ± SE, p<0.05. While not significant difference was found in ERRγ1 mRNA from PT compare to AGA1 (GA:37-38w), 1.13 ± 0.26 vs 1.11 ± 0.25 AU,mean ± SE.Total Aro was higher in PT vs AGA (8.91±3.35 vs 1.74±0.41AU,mean ± SE),while was lower in LGA vs AGA (0.81±0.36 vs 2.29±0.68), p<0.05. Analysis of Active transcript variant related to total Aro showed that ActAro/TotAro ratio was higher in PT (2.26±0.26 vs AGA: 0.70±0.23) and in LGA (2.42±0.31 vs AGA: 1.47 ± 0.28), p<0.05. We have found a higher expression of ERRγ1 as well as ActAro/TotAro ratio in PL from LGA compare to AGA2. On the other hand, in PT no significant difference in ERRγ1 expression compare to AGA1 was found, although there is a significant higher TotAro mRNA expression and ActAro/TotAro ratio. These results suggest that ERRγ1 is involved in the regulation of Active Aro variant expression in PL from LGA newborns but it would not be involved in PT. Taken together these results it could be suggested that the interplay between ERRγ1 and estrogen production in human PL might be involved in the regulation of fetal programming in LGA newborns.