Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development

Frontiers in Genetics

Dawn L. DeMeo¹  Carrie A. Vyhlidal²  Katerina Kechris³  Cheyret Wood³  Cuining Liu³  Ivana V. Yang⁴  Shuyu Ye⁶  Vong L. Smith⁶  Nancy W. Lin⁶  Margaret H. Cruse⁶  Sunita Sharma⁶  Lisa A. Maier⁷ 

[1] Channing Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United States;Children’s Mercy Hospital and Clinics, Kansas City, MO, United States;Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, United States;Division of Bioinformatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States;Division of Environmental and Occupational Health, National Jewish Health, Denver, CO, United States;Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States;Environmental and Occupational Health, Colorado School of Public Health, Aurora, CO, United States;

关键词: microRNA;    lung development;    pulmonary disease;    sex-specific;    gene expression;    human;   

DOI  :  10.3389/fgene.2022.762834

来源: DOAJ

【 摘 要 】

Background: Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differences in prevalence. The developmental origins of health and disease hypothesis suggests that these sex-specific differences in fetal lung development may influence disease susceptibility later in life. In this study, we performed miRNA sequencing on human fetal lung tissue samples to investigate differential expression of miRNAs between males and females in the pseudoglandular stage of lung development. We hypothesized that differences in miRNA expression are present between sexes in early human lung development and may contribute to the sex-specific differences seen in pulmonary diseases later in life.Methods: RNA was isolated from human fetal lung tissue samples for miRNA sequencing. The count of each miRNA was modeled by sex using negative binomial regression models in DESeq2, adjusting for post-conception age, age2, smoke exposure, batch, and RUV factors. We tested for differential expression of miRNAs by sex, and for the presence of sex-by-age interactions to determine if miRNA expression levels by age were distinct between males and females.Results: miRNA expression profiles were generated on 298 samples (166 males and 132 females). Of the 809 miRNAs expressed in human fetal lung tissue during the pseudoglandular stage of lung development, we identified 93 autosomal miRNAs that were significantly differentially expressed by sex and 129 miRNAs with a sex-specific pattern of miRNA expression across the course of the pseudoglandular period.Conclusion: Our study demonstrates differential expression of numerous autosomal miRNAs between the male and female developing human lung. Additionally, the expression of some miRNAs are modified by age across the pseudoglandular stage in a sex-specific way. Some of these differences in miRNA expression may impact susceptibility to pulmonary disease later in life. Our results suggest that sex-specific miRNA expression during human lung development may be a potential mechanism to explain sex-specific differences in lung development and may impact subsequent disease susceptibility.

【 授权许可】

Unknown