Biomedical researchers have long relied more heavily on male animals and cell lines than female ones, and even some clinical studies have overlooked the effects of drugs or other medical interventions on women. Earlier this year, an analysis of more than 2,000 research papers from five surgical journals documented this bias.
“Women make up half the population, but in surgical literature, 80 percent of the studies only use males,” study coauthor Melina Kibbe of Northwestern Medicine said in an August press release.
In response, editors of the journals in question said that they would require study authors to indicate the sex of animals and cell lines used in their experiments, and to provide a legitimate rationale for studies that use only one sex.
This disparity has also spurred policy changes at the US National Institutes of Health (NIH). In May, NIH director Francis Collins and associate director of Research on Women’s Health Janine Clayton announced that grant applicants would soon be required to consider both sexes in preclinical research proposals. In September, the NIH publicized $10 million in grant funding to support the study of sex differences in areas such as drug addiction, immunology, and cardiovascular health.
Meanwhile, new research has implicated the male-specific Y chromosome in a range of activities—not all related to sexual development. Two studies published in Nature earlier this year compared the sex chromosomes among a related variety of animals. Although the Y chromosome maintains only 3 percent of its ancestral genes, many of these genes participate in key regulatory functions, the researchers found.
Indeed, scientists examining data from longitudinal studies of more than 6,000 men found that cigarette smoking was associated with loss of the Y chromosome in blood cells, which increased the risk for various types of cancer. While the mechanistic relationship between Y chromosome loss and cancer is still unclear, the results could explain why men tend to have higher rates of lung and other cancers than women.
On the other hand, Alzheimer’s disease is more common among women. In a study published earlier this year in the Annals of Neurology, researchers analyzing genetic data from more than 8,000 people found that a genetic variant at APOE had a greater effect on the risk of Alzheimer’s in women than in men. This disparity may result from a connection between APOE genotype and estrogen activity.
Another genetic study of children with autism and their families hinted at resilience in the female brain. Researchers found that girls with autism harbored more copy number variations and single-nucleotide polymorphisms than their male counterparts. The result suggested that “there’s something that’s protecting [female] brain development,” study coauthor Sébastien Jacquemont from the University Hospital of Lausanne in Switzerland told New Scientist.
Scientists examining mating behavior in a small winged insect from Brazil, Neotrogla, discovered an unusual sex reversal in the animals’ genitals: The female penetrates a chamber inside the male with an “elaborate penis-like organ” dubbed a “gynosome.” This penetration keeps the pair together during days of copulation, in which the female receives a nutrient-packed seminal gift.
Another female-driven reproductive process may occur within the oviducts of pigs, researchers reported this May in BMC Genomics. The scientists introduced only X-chromosome-carrying sperm cells into one oviduct of a sow and Y-chromosome-carrying sperm into the other oviduct. Gene expression profiles of the two oviducts showed that 501 genes were differentially expressed. While intriguing, the experiment included just four animals, and the results didn’t indicate whether the female oviduct exerts any selection on sperm cells.
Clarification (December 29): This article has been updated from a previous version to clarify that the NIH issued a Request for Information on considering both sexes in preclinical research proposals, which closed in October. No new guidelines have yet been set.