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Sex of the cell dictates its response: differential gene expression and sensitivity to cell death inducing stress in male and female cells
Author(s) -
Penaloza Carlos,
Estevez Brian,
Orlanski Shari,
Sikorska Marianna,
Walker Roy,
Smith Catherine,
Smith Brandon,
Lockshin Richard A.,
Zakeri Zahra
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-119388
Subject(s) - sexual dimorphism , biology , hormone , sexual differentiation , sex characteristics , endocrinology , gene expression , medicine , fetus , physiology , andrology , gene , pregnancy , genetics
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.—Penaloza, C.,Estevez, B., Orlanski, S., Sikorska, M.,Walker, R., Smith, C., Smith, B., Lockshin R.A., Zakeri, Z. Sex of the cell dictates its response: differential gene expression and sensitivity to cell death inducing stress in male and female cells. FASEB J. 23, 1869–1879 (2009)