Male or Female? Why a Cell's Sex Matters

Male or Female? Why a Cell's Sex Matters
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It may surprise you to learn that -- like humans -- cells can be male or female. The distinction is more subtle at the cellular level, but it can actually affect how cells react in a variety of experiments. Still, many scientists don't take into account the sex of their cells. According to a new review published in the

A good chunk of scientific research is performed in vitro. These experiments are undertaken using components of an organism rather than the whole organism, itself. For example, if a researcher has a disease treatment or biological theory they'd like to examine, they'll often start by testing it on lines of cells; they won't simply jump into animal tests.

Each cell line is derived from a single donor, and like every cell in the human body, each of the acquired cells contains 23 pairs of coiled DNA, called chromosomes. Included in this group are the two sex chromosomes: simply dubbed X and Y. Cells in women's bodies have two X chromosomes (XX), while cells in men's bodies have one X and one Y (XY). Thus, we get our male and female cells. Approximately 5% of the human genome resides on these chromosomes -- 1,846 genes on the X and 454 on the Y. This means that male and female cells are fundamentally dissimilar on a genetic level.

The scientists behind the new review, Kalpit Shah, Charles McCormack, and Neil Bradbury, all professors at Chicago Medical School of Rosalind Franklin University, say that these differences are often ignored, despite the fact that genes expressed on sex chromosomes can impact cell function and how they react to all sorts of stimuli.

Previous research has made this clear. Cultured female neurons uptake dopamine -- a neurotransmitter that helps regulate feelings of pain and pleasure -- twice as quickly as male neurons. Female neurons and kidney cells are also more susceptible to chemical agents that lead to programmed cell death. And female liver cells contain more of the gene CYP3A. This last difference is especially crucial, as the actions of CYP3A account for how over half the drugs on the market today are metabolized!

"Thus, for 50% of prescription drugs, the effectiveness of a particular drug dosage... may be quite different in females compared to males," the authors explain. Consider this possible side effect: women are 50 to 75 percent more likely than men to experience an adverse drug reaction. This is caused by a wide range of factors, chiefly because females weigh less, but cellular mechanisms undoubtedly contribute to it.

Such a statistic makes it clear than researchers should consider the sex of their cell lines when testing drugs in vitro, as the effects on male and female lines may not be the same. But it may be even more important when it comes to stem cells, as male and female varieties are decidedly not created equal.

"Female muscle-derived stem cells are less sensitive to oxidative stress and regenerate skeletal muscle much more efficiently than muscle-derived stem cells from their male counterparts," the authors write. "[This] is likely to have a big impact upon other stem cell mediated therapies, should the findings be replicated for other diseases.

Over the years, differences in disease rates and drug effects among males and females have often been attributed to variations in hormone levels. But it's entirely possible that many of these dissimilarities result from underlying differences at the cellular level. Like people, cells are also male and female, and they are plainly not the same. Their unique characteristics must be accounted for in scientific research.

Souce: Kalpit Shah, Charles E McCormack, Neil A Bradbury. "Do you know the sex of your cells?" American Journal of Physiology - Cell Physiology. Published 6 November 2013. Vol. no. DOI: 10.1152/ajpcell.00281.2013

(Image: Cell Culture via Shutterstock)

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