Variation of microRNA expression in the human placenta driven by population identity and sex of the newborn

• Type of Material: Article
• Authors: Song Guo, Skolkovo Institute of Science & Technology; Shuyun Huang, Chinese Academy of Sciences; Xi Jiang, Chinese Academy of Sciences; Haiyang Hu, Chinese Academy of Sciences; Dingding Han, Chinese Academy of Sciences; Carlos Moreno, Emory University; Genevieve L. Fairbrother, Obstet & Gynecol Atlanta; David A. Hughes, University of Bristol; Mark Stoneking, Max Planck Inst Evolutionary Anthropol; Philipp Khaitovich, Skolkovo Institute of Science & Technology
• Language: English
• Date: 2021-04-20
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s). 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12864-021-07542-0
• Title of Journal or Parent Work: BMC Genomics
• Volume: 22
• Issue: 1
• Start Page: 286
• End Page: 286
• Grant/Funding Information: D.A.H. and M.S. are grateful for the support of the Max Planck Society. D.A.H. is supported by the Wellcome Investigator Award (202802/Z/16/Z).; This work was financially supported by the National Natural Science Foundation of China (Grants 91331203 to P.K.) and the National One Thousand Foreign Experts Plan (Grant WQ20123100078 to P.K.)
• Keywords: Sexual dimorphism; Life Sciences & Biomedicine; Genetics & Heredity; Placenta; Selection; Human; Biotechnology & Applied Microbiology; Populations; Science & Technology; Newborn; Copy-number variation; Imprinting; Genomics; Gene expression; Impact; Patterns; Mirna expression; miRNA; Evolution
• Research Categories: Health Sciences, Nutrition; Health Sciences, Pathology; Health Sciences, Obstetrics and Gynecology; Biology, Genetics

Abstract

Background Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts. Here, we analyzed microRNA (miRNA) expression in human placental samples derived from 36 individuals representing four genetically distinct human populations: African Americans, European Americans, South Asians, and East Asians. All samples were collected at the same hospital following a unified protocol, thus minimizing potential biases that might influence the results. Results Sequence analysis of the miRNA fraction yielded 938 annotated and 70 novel miRNA transcripts expressed in the placenta. Of them, 82 (9%) of annotated and 11 (16%) of novel miRNAs displayed quantitative expression differences among populations, generally reflecting reported genetic and mRNA-expression-based distances. Several co-expressed miRNA clusters stood out from the rest of the population-associated differences in terms of miRNA evolutionary age, tissue-specificity, and disease-association characteristics. Among three non-environmental influenced demographic parameters, the second largest contributor to miRNA expression variation after population was the sex of the newborn, with 32 miRNAs (3% of detected) exhibiting significant expression differences depending on whether the newborn was male or female. Male-associated miRNAs were evolutionarily younger and correlated inversely with the expression of target mRNA involved in neuron-related functions. In contrast, both male and female-associated miRNAs appeared to mediate different types of hormonal responses. Demographic factors further affected reported imprinted expression of 66 placental miRNAs: the imprinting strength correlated with the mother’s weight, but not height. Conclusions Our results showed that among 12 assessed demographic variables, population affiliation and fetal sex had a substantial influence on miRNA expression variation among human placental samples. The effect of newborn-sex-associated miRNA differences further led to expression inhibition of the target genes clustering in specific functional pathways. By contrast, population-driven miRNA differences might mainly represent neutral changes with minimal functional impacts.