Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

Rosaria Varì,Beatrice Scazzocchio,Tiziana Filardi,Carmela Santangelo,Roberta Masella,Anna Citarella,Maria Bellenghi

doi:10.3390/biomedicines9111509

Rosaria Varì, Beatrice Scazzocchio + Show 5 more

Open Access

https://doi.org/10.3390/biomedicines9111509

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Abstract

In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders.

Highlights

Results showed that among the 18 miRNAs changed in GDM-amniotic fluid (AF), a significant increase in miR-378a-3p, miR-885-5p, and miR-7-1-3p was observed in AF samples from female offspring, whereas only miR-199a-3p increased in the male ones
The overexpression of the abovementioned miRNAs reduced the expression of the target genes ABCA1, PAK4, and INSR involved in cholesterol delivery in the liver and placenta, in hepatocyte proliferation, and fetal growth, respectively
This review is focused on the presence, expression, and function of noncoding RNAs (ncRNAs) in relation to placental function, fetal development, and maternal pregnancy-related diseases, considering possible clinical differences depending on the sex of the fetus

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Noncoding RNAs modulate different biological processes due their capability to regulate gene expression at both the transcriptional and post-transcriptional level [17] They modulate cell differentiation and sex differentiation and sex-specific tissue development and/or function, as well as initiation and progression of multiple diseases [17,18] (Figure 1). LncRNAs modulate a wide variety of biological processes, such as cellular differentiation, maintenance of stem cell pluripotency, and development of tissues and organs, contributing to the onset of human diseases [17,43] They are implicated in different pregnancy-related complications, including preeclampsia [44], GDM [45], intrauterine growth restriction (IUGR) [46], and missed abortions [47]. The increasing knowledge about the association between ncRNA profiles and human pregnancy-related conditions suggests that these classes of RNAs might act as feasible and useful biomarkers for several diseases (Figure 2)

The Importance of Sexual Dimorphism in Placental ncRNAs Expression

Sex-Based ncRNAs Expression in Fetal Development

Conclusions