In my lab, we use exclusively female mice to study Sjogren's disease because in humans it is a female-predominant disease but also because only female mice developed a strong enough salivary gland phenotype to reliably study. This is despite many researchers looking into female biochemistry such as hormones and the estrous cycle trying to explain this phenomenon and coming up empty. Additionally, this female predominance is consistent among many of Sjogren's models where male mice just don't develop a reliable phenotype. So despite not being exclusive to females in humans and mice, we have to use female mice to efficiently study the salivary gland component of Sjogren's disease. Conversely, we also study oral cancer which we use only males because it has a slight bias towards males in humans but also we can make use of all the males generated and not used in our Sjogren's research. The latter is slightly problematic because many researchers believe that the slight male bias of oral cancer is due to behavioral differences between male and female humans such as male men smoking and drinking more (on average) than female women.

Thank you very much for your insight Kevin Muñoz Forti I have read several articles in oral cancer as well as colon cancer where they have chosen female mice over male without giving any specific reason as to why they did so

Hello V H Krishna Prasad

Yes, you are right. Sometimes scientists deliberately choose male mice, because they worry that the cycling reproductive hormones in female animals might make it harder to interpret the results. It also appears that males are sometimes favored because that's simply the conventional thing to do.

Now, choosing male or female mice will depend on your protocol and the disease you may want to study. For instance, if you may want to test any particular treatment for a female-related disease, then you will have to use female mice. While choosing male or female you need to bear in mind the different hormones that are at play in male mice and female mice, and whether these hormones could influence your experimental endpoint.

As far as colon cancer is concerned, a higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival.

This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling.

For more information you may refer to the article attached below.

https://www.frontiersin.org/articles/10.3389/fonc.2020.607909/full

There is a large body of literature on sexual dimorphism in a wide number of cancers, the majority of which show male predominance with notable exceptions of breast and thyroid cancer, which are female dominant.

Some studies have used animal models to test the effect of testosterone on CRC tumorigenesis. For instance, rat harboring an Apc non-sense mutation in heterozygosis leads to spontaneous colonic tumors. These tumors occur in greater numbers in male compared to female rats, mimicking the human sexual dimorphism. Males also develop a larger number of adenomas in the AOM mouse in which the mutagenic agent azoxymethane induces spontaneous colonic carcinogenesis. Castration decreases the number of developed colonic adenomas in both, the rat harboring an Apc non-sense mutation as well as in the AOM mouse models.

As far as oral cancer is concerned, I agree with Kevin Muñoz Forti . The oral cavity and oropharyngeal cancers are twice as common in men than in women. This might be because men have been more likely to use tobacco and alcohol in the past. Also, HPV-related oropharyngeal cancers are also seen more often in men.

Best.

Thank you very much for this information Malcolm Nobre , However I don't still get why certain well established studies on oral cancer, like the ones published in Nature (https://www.nature.com/articles/s41467-019-13471-0#Sec8) selected female mice over male, while it is evident that oral cancer is more common in males than in females.

Hello V H Krishna Prasad

You are right, many researchers still avoid using female animals. As discussed here, it's important to consider how frequent a condition is in each sex. In 2015 NIH released a policy about considering sex as a biological variable, but still, it hasn't reached the same level. I'll attach some papers s you can follow the discussion on the inclusion of female animals in animal sciences.

Article Battle of the sexes: who is more variable, and does it really matter?

Article Impaired discriminative avoidance and increased plasma corti...

Article Inclusion of females does not increase variability in rodent...

Article Female rats are not more variable than male rats: A meta-ana...

Article O viés de gênero na neurociência comportamental

Article Breaking the Cycle: Estrous Variation Does Not Require Incre...

Article Sex Bias in Neuroscience and Biomedical Research

Article Males still dominate animal studies

Article Mouse spontaneous behavior reflects individual variation rat...

Article Pervasive Neglect of Sex Differences in Biomedical Research

Thank you very much for sharing this Marcela Becegato