BRCA1 Gene Mutation Linked To Breast Cancer Risk May Also Increase Sense Of Smell And Fertility

Sense of smell
A new study may have found the BRCA1 mutation linked to breast cancer may be beneficial when it comes to fertility. Dennis Wong, CC BY 2.0

Is there an advantage to having the BRCA1 mutation — a mutation known to increase the risk of developing breast and ovarian cancer? It may be hard to believe, but researchers from the University of Southern California-Los Angeles and University College London have found that mice carriers of the mutation experience greater olfactory gene expression. In other words, mice with the mutation have a greater sense of the smell, and it may positively impact fertility.

Let's back up: BRCA1 mutations are the mice equivalent of human BRCA1 mutations, and the mutations remain the greatest risk factor for hereditary tumors, researchers said. But the estrous cycle — the menstrual cycle in humans — remains the greatest risk factor for sporadic tumors, or the tumors that develop with little or no family history of cancer. Since prior research has shown female mice with the mutation, although fertile, endure the proestrus phase of their cycle even longer than their post-estrus phase (pre-ovulation), researchers set out to see how the mutation influences cycle regulation.

They used a total of four mice, two of which carried the mutation and two that did not. Each mouse was inoculated with 5 IU of pregnant mare serum so that their estrous cycles were in-sync; then, both ovaries were collected and pooled from each mouse. In order to compare this to humans, researchers collected ovarian granulosa cells of in vitro fertilization procedures, with the eggs eventually being removed under microscopic inspection; the same was done in mice following ovary extraction.

In mice, reserachers found that "several of the genes that were upregulated in both mutant animals belong to the olfactory receptor family." These receptors are also known as the smell receptors, and they detect odor molecules. Put it another way: Mice carrying the BRCA1 mutation in their ovarian granulosa cells were more responsive to smells than mice that did not have the mutation.

The advantage of mice having this mutation slash sense of smell was seen when isolated female mice were reintroduced to an environment also housing male mice. Female mice's ovarian tissue revealed that when in this mixed environment, male scent led to more intense activity in female's protein levels, suggesting the possibility that carrying the BRCA1 mutation makes women more responsive to sexual pheromones; olfactory receptors belong to the G-protein-couple receptor family.

"While the possibility remains that this increase is due to activation of another G-protein-couple receptive…the data are compatible with the idea that absence of an active BRCA1 protein in ovarian granulose cells leads to increase olfactory receptor signaling in these cells," researchers said.

That said, researchers pointed out that "granulosa cells are not the site of original of the cancers that typically developing in BRCA1 mutation carriers, even in those who develop BRCA1-associated malignancies."

"We suggested earlier that the BRCA1 mutation carrier state in humans, in spite of its association with increased cancer risk, might confer some phenotypic advantages such as reduce predisposition to bone fractures due to increase estrogen exposure," they added. "Our results point to yet another potential benefit of the BRCA1 mutation carrier state, that of increase responsive to olfactory stimuli possibly impacting fertility, which may have contribute to maintain such mutations in the human gene pool."

Researchers concluded that if their data is applicable to humans, it would suggest that "the menstrual cycle is especially sensitive to olfactory ligands in BRCA1 mutation carriers." It would also raise important questions of "whether or not interference with specific olfactory agents could be an effective means of reducing cancer risk in young individuals with germline BRCA1 mutations who wish to postpone risk-reducing surgery in order to preserve their fertility."

Source: Liu Y, Pike MC, Wu N, Lin YG, Mucowski S, Punj V, et al. (2015) Brca1 Mutations Enhance Mouse Reproductive Functions by Increasing Responsiveness to Male-Derived Scent. PLOS ONE. 2015.

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