Redução da o-glicosilação com n-acetilglucosamina no tecido placentário acarreta em prejuízo no desenvolvimento placentário e fetal frente a desordens hipertensivas da gestação

Abstract

Pregnancy upon hypertension condition is related to complications of placental function, reduced blood flow in this organ and the transfer of nutrients and oxygen, which can result in consequences for gestational and fetal development. O-glycosylation with Nacetylglucosamine (O-GlcNAc) is a post-translational modification (MPT) modulating several signaling pathways. Studies demonstrate that O-GlcNAc is essential for mammalian embryogenesis, involved in the formation of the blastocyst and metabolic differentiation during the implantation period. The increase in this MPT leads to a decrease in cell proliferation and a reduction in the formation of the blastocyst, playing a critical role in the early stages of fetal development. However, few studies are evaluating the expression of O-GlcNAc in placental tissue at different stages of hypertensive pregnancy and its relationship with changes in gestational and fetal parameters. This study aimed to characterize maternal and fetal gestational parameters and the profile of placental O-GlcNAc in spontaneously hypertensive rats (SHR) and pregnant Wistar rats with 14 and 20 days of pregnancy. Upon approval of the ethics committee on animal experimentation (23108.038471/2019-14 (CEUA-UFMT) female SHR and Wistar rats (12 to 14 weeks), from the UFMT Experimental Animal Maintenance Center, were divided into hypertensive and normotensive groups with gestational periods of 14 [SHR (n = 6) and Wistar (n = 6)] and 20 days [SHR (n = 6) and Wistar (n = 6)] of pregnancy. After measuring systolic blood pressure (SBP), both groups underwent mating and monitoring of gestational weight gain after confirmation of pregnancy. At the end of the established gestational periods, the rats were killed for the evaluation of gestational and fetal parameters, and Western Blot was performed to quantify O-GlcNAc in the placenta. The results were expressed using mean ± SEM, and for statistical analysis, t-test Student or analysis of variance ANOVA One-Way. Hypertensive rats presented high levels of SBP [mmHg (180 ± 3 vs. 127 ± 5 normotensive group) p<0,0001] and reduced O-GlcNAc expression in placental tissue at 14 [(1,10 ± 0,15 vs. 2,67 ± 0,4 normotensive group) p= 0,0032] and 20 days [(2,18 ± 0,1 vs. 3,20 ± 0,4 normotensive group) p = 0.0254], compared to normotensive rats. The hypertensive group had lower gestational weight gain at 14 and 20 days, lower fetal weight at 14 [(g) 0,12 ± 0,007 vs. 0,15 ± 0,004 normotensive group (p = 0.0282)] and 20 days [(g) 3,41 ± 0,06 vs. 5,07 ± 0,07 normotensive group (p <0.0001)], reduced placental efficiency [(g) 6,13 ± 0,22 vs. 10,56 ± 0,2 normotensive group (p < 0.0001)] and increased placental weight [(g) 0,57 ± 0,02 vs. 0,48 ± 0,01 normotensive group (p = 0.0065) in 20 days and increased pre-implantation losses in 14 [3,8 ± 0,7 vs. 1,2 ± 0,4 normotensive group (p= 0,0135)] and 20 days [4,33 ± 1,7 vs. 0,33 ± 0,2 normotensive group (p= 0,0461)]. Given the above, the present work shows that reduced placenta levels of O-GlcNAc are involved with changes in fetal-placental development in a pregnancy affected by hypertensive conditions.