Sexually Dimorphic Transcriptomic Changes of Developing Fetal Brain Reveal Signaling Pathways and Marker Genes of Brain Cells in Domestic Pigs

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Sep 28

PMID 34572090

Citations 3

Authors

Monica Strawn

Joao G N Moraes

Timothy J Safranski

Susanta K Behura

Affiliations

Soon will be listed here.

Abstract

In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.

Citing Articles

Incidence of alternative splicing associated with sex and opioid effects in the axon guidance pathway.

Southey B, Sunderland G, Gomez A, Bhamidi S, Rodriguez-Zas S Gene. 2025; 942:149215.

PMID: 39756548 PMC: 11863264. DOI: 10.1016/j.gene.2025.149215.

Sex-bias metabolism of fetal organs, and their relationship to the regulation of fetal brain-placental axis.

Poudel S, Behura S Metabolomics. 2024; 20(6):126.

PMID: 39495316 DOI: 10.1007/s11306-024-02189-w.

Porcine Astrocytes and Their Relevance for Translational Neurotrauma Research.

Purvis E, Fedorczak N, Prah A, Han D, ODonnell J Biomedicines. 2023; 11(9).

PMID: 37760829 PMC: 10525191. DOI: 10.3390/biomedicines11092388.

Role of caveolin-1 in metabolic programming of fetal brain.

Islam M, Behura S iScience. 2023; 26(10):107710.

PMID: 37720105 PMC: 10500482. DOI: 10.1016/j.isci.2023.107710.

References

Zeltser L, Leibel R . Roles of the placenta in fetal brain development. Proc Natl Acad Sci U S A. 2011; 108(38):15667-8. PMC: 3179106. DOI: 10.1073/pnas.1112239108. View

Holland P, Takahashi T . The evolution of homeobox genes: Implications for the study of brain development. Brain Res Bull. 2005; 66(4-6):484-90. DOI: 10.1016/j.brainresbull.2005.06.003. View

Vom Saal F . Sexual differentiation in litter-bearing mammals: influence of sex of adjacent fetuses in utero. J Anim Sci. 1989; 67(7):1824-40. DOI: 10.2527/jas1989.6771824x. View

Hosoya K, Tachikawa M . Roles of organic anion/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol. 2011; 15(4):478-85. DOI: 10.1007/s10157-011-0460-y. View

Horvath S . DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14(10):R115. PMC: 4015143. DOI: 10.1186/gb-2013-14-10-r115. View

Jang Y, Ma Y, Lindemann M . Intrauterine position affects fetal weight and crown-rump length throughout gestation. J Anim Sci. 2014; 92(10):4400-6. DOI: 10.2527/jas.2014-7762. View

Meyer P, Lafitte F, Bontempi G . minet: A R/Bioconductor package for inferring large transcriptional networks using mutual information. BMC Bioinformatics. 2008; 9:461. PMC: 2630331. DOI: 10.1186/1471-2105-9-461. View

Monzon-Sandoval J, Castillo-Morales A, Urrutia A, Gutierrez H . Modular reorganization of the global network of gene regulatory interactions during perinatal human brain development. BMC Dev Biol. 2016; 16:13. PMC: 4866393. DOI: 10.1186/s12861-016-0111-3. View

Wickens M, Bangasser D, Briand L . Sex Differences in Psychiatric Disease: A Focus on the Glutamate System. Front Mol Neurosci. 2018; 11:197. PMC: 5996114. DOI: 10.3389/fnmol.2018.00197. View

10.

Zhao J, Tian Y, Zhang H, Qu L, Chen Y, Liu Q . p53 Mutant p53 Induces Neural Tube Defects in Female Embryos. Int J Biol Sci. 2019; 15(9):2006-2015. PMC: 6743294. DOI: 10.7150/ijbs.31451. View

11.

Steuer R, Kurths J, Daub C, Weise J, Selbig J . The mutual information: detecting and evaluating dependencies between variables. Bioinformatics. 2002; 18 Suppl 2:S231-40. DOI: 10.1093/bioinformatics/18.suppl_2.s231. View

12.

Wozniak D, Dikranian K, Ishimaru M, Nardi A, Corso T, Tenkova T . Disseminated corticolimbic neuronal degeneration induced in rat brain by MK-801: potential relevance to Alzheimer's disease. Neurobiol Dis. 1999; 5(5):305-22. DOI: 10.1006/nbdi.1998.0206. View

13.

De Lacoste M, Horvath D, Woodward D . Possible sex differences in the developing human fetal brain. J Clin Exp Neuropsychol. 1991; 13(6):831-46. DOI: 10.1080/01688639108405101. View

14.

Ryan B, Vandenbergh J . Intrauterine position effects. Neurosci Biobehav Rev. 2002; 26(6):665-78. DOI: 10.1016/s0149-7634(02)00038-6. View

15.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

16.

Vodicka P, Smetana Jr K, Dvorankova B, Emerick T, Xu Y, Ourednik J . The miniature pig as an animal model in biomedical research. Ann N Y Acad Sci. 2005; 1049:161-71. DOI: 10.1196/annals.1334.015. View

17.

Zhang Y, Chen K, Sloan S, Bennett M, Scholze A, OKeeffe S . An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014; 34(36):11929-47. PMC: 4152602. DOI: 10.1523/JNEUROSCI.1860-14.2014. View

18.

Monteagudo A, Timor-Tritsch I . Normal sonographic development of the central nervous system from the second trimester onwards using 2D, 3D and transvaginal sonography. Prenat Diagn. 2008; 29(4):326-39. DOI: 10.1002/pd.2146. View

19.

McCarthy M . Multifaceted origins of sex differences in the brain. Philos Trans R Soc Lond B Biol Sci. 2016; 371(1688):20150106. PMC: 4785894. DOI: 10.1098/rstb.2015.0106. View

20.

Goggolidou P, Soneji S, Powles-Glover N, Williams D, Sethi S, Baban D . A chronological expression profile of gene activity during embryonic mouse brain development. Mamm Genome. 2013; 24(11-12):459-72. PMC: 3843766. DOI: 10.1007/s00335-013-9486-7. View