Sex of the cell dictates its response: Differential gene expression and sensitivity to cell death inducing stress in male and female cells

Carlos Penaloza, Brian Estevez, Shari Orlanski, Marianna Sikorska, Roy Walker, Catherine Smith, Brandon Smith, Richard A. Lockshin, Zahra Zakeri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Sexual dimorphisms are typically attributed to the hormonal differences arising once sex differentiation has occurred. However, in some sexually dimorphic diseases that differ in frequency but not severity, the differences cannot be logically connected to the sex hormones. Therefore, we asked whether any aspect of sexual dimorphism could be attributed to chromosomal rather than hormonal differences. Cells taken from mice at d 10.5 postconception (PC) before sexual differentiation, at d 17.5 PC after the first embryonic assertion of sexual hormones, and at postnatal day 17 (puberty) were cultured and exposed to 400 μM ethanol or 20 μM camptothecin or to infection with influenza A virus (multiplicity of infection of 5). The results showed that untreated male and female cells of the same age grew at similar rates and manifested similar morphology. However, they responded differently to the applied stressors, even before the production of fetal sex hormones. Furthermore, microarray and qPCR analyses of the whole 10.5 PC embryos also revealed differences in gene expression between male and female tissues. Likewise, the exposure of cells isolated from fetuses and adolescent mice to the stressors and/or sex hormones yielded expression patterns that reflected chromosomal sex, with ethanol feminizing male cells and masculinizing female cells. We conclude that cells differ innately according to sex irrespective of their history of exposure to sex hormones. These differences may have consequences in the course of sexually dimorphic diseases and their therapy.

Original languageAmerican English
Pages (from-to)1869-1879
Number of pages11
JournalFASEB Journal
Volume23
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Estrogen
  • Ethanol
  • Gender
  • Testosterone

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