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Sex differences in gene expression of developing fetal brain in pig

ABSTRACT: In this study, gene expression was profiled by RNA-seq to examine whole transcriptome of the male and female fetal brain of domesticated pig on the three gestation days 45, 60 and 90. Gene expression in fetal brain was distinct on day 90 compared to days 45 and 60. The homeobox genes were consistently upregulated in the brain of females compared to males during development. The sex of adjacent fetuses influenced gene expression of fetal brain. Extensive exon-level expression changes in the developing brains was observed. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in female brain only whereas receptor mediated signaling pathways were enriched in the male brain alone. Genes that are known markers of neurons and astrocytes were differentially regulated in male and female brain during development. The study further suggests that regulation of ion transportation via placental matrotrophy may play a role in fetal brain development.

ORGANISM(S): Sus scrofa

PROVIDER: GSE178970 | GEO | 2021/09/29

REPOSITORIES: GEO

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Project description:Purpose: Next generation bulk RNA sequencing of a large group (37 individuals) of matched tissues (fetal brain and fetal placenta) from human fetuses collected via elective termination at 72-82 days post conception (d.p.c.), a timeframe that closely matches the embryonic developmental window used in our mouse studies (14.5-16.5) Methods: Human placenta (maternal decidua separated from fetal placenta) and fetal brain tissues were obtained from the NIH-supported Laboratory of Developmental Biology at the University of Washington between the years 1999 and 2010 and used under a protocol approved by the Duke University Institutional Review Board (Pro00014066). Tissue specimens were stored at -80°C until required for RNA or protein extraction. Prior to collection, informed consent was obtained from all individuals undergoing the elective termination. RNA from human tissue was prepared for sequencing using an Illumina TrueSeq RNA Exome kit and sequenced on an Illumina NovaSeq 6000 configured for a S2 flow cell at 50bp PE. Results: PCR for the Y chromosome (SRY) identified 17 male and 20 female fetal tissue sets, with the average age of 78.2 d.p.c. for both sexes. No maternal data were available, so we assessed decidual triglyceride accumulation to use as a proxy for maternal weight, given that women with overweight/obesity exhibit triglyceride accumulation in the placenta. Triglyceride levels trended higher in pregnancies with female fetuses, but there was no significant difference between triglyceride accumulation in decidua associated with male or female pregnancies. Pearson's Correlation of gene expression with maternal triglyceride accumulation from bulk RNA-seq from 16 matched male and 19 matched female brain and placenta samples revealed a strong dimorphic trend in gene expression. In male pregnancies, differentially correlated genes were predominantly over-expressed with increasing maternal weight (i.e. gene expression increased as maternal triglycerides increased); the opposite effect was seen in female pregnancies. In the male brain, only 45 genes significantly correlated with maternal triglyceride accumulation (either positive or negative), whereas 781 genes were significantly correlated in females.

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Sex differences in gene expression of developing fetal brain in pig

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