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

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 microM ethanol or 20 microM 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.

Sex differences in developmental programming models

“…Cells derived from day 10.5 mouse embryos and grown in culture show similar patterns and rates of cell division irrespective of chromosomal sex but differ in their sensitivity to applied insults (e.g. ethanol) with female lineages showing higher rates of cell death (Penaloza et al 2009). …”

Sex redefined

“…"To tell you the truth, it's actually kind of surprising how big an effect of sex chromosomes we've been able to see, " says Arnold. He and his colleagues have shown 17 that the dose of X chromosomes in a mouse's body can affect its metabolism, and studies in a lab dish suggest 18 …”

Nutritional developmental epigenomics: immediate and long-lasting effects

“…However, this proposal does not take into account the many important effects of perinatal secondary sexual differentiation and may only be true for a minority of sex-related traits. Recently, it has been demonstrated that sexual dimorphism can be attributed also to the sex chromosomes (76) . Using cells that were harvested from embryonic mice before sexual differentiation on day 10 .…”