Before the widespread use of transgenic mice, reproductive physiologists had limited means of studying the effects of sex (or gender) on behavioral and physiological processes; most studies would remove an animal’s gonads, causing the (sex) hormonal environment to be somewhat ‘equal,’ and then would restore the circulation or do a swap replacement (androgens to females, estrogens to males). Nowadays, we have access to the four core genotype line (well, some of us do) in which the sex chromosome complement can oppose the gonadal phenotype, essentially creating mice with gender identity disorder–XX mice with testes and XY mice with ovaries. This is due to a spontaneous deletion of the Sry gene, which dictates the development of testes. I’ve discussed alcohol-related research in these mice prior.
Very recently, some West Coast circadian biologists examined circadian rhythms in this line at behavioral, physiological, and molecular levels. Although the differences were subtle, there were certain time points and circumstances wherein the influences of sex chromosomes or sex hormones were apparent. First, the mice were put on running wheels, and it was found that the mice with female sex chromosomes (XX males and XX females) were active longer during the night compared to mice with male sex chromosomes (XY females and XY males) when the animals were housed under constant darkness. This is interesting because wild-type females with circulating estrogens also have longer periods of nighttime activity under constant darkness, suggesting that this sex difference may be mediated by the sex chromosomes. The researchers also investigated how the animals would shift (delay) their rhythms of wheel running in response to light in the early part of the night. There were apparent differences in XX and XY females versus XX and XY males with intact gonads, with the females having larger phase-delays, but these differences completely disappeared when the gonads were removed. Under this circumstance, this would suggest that sex differences in response to light may be mediated by sex hormones.
The researchers also looked at in vitro rhythms of the master circadian clock (the SCN) and peripheral tissues (adrenals and liver). But this wasn’t in the transgenic mice, just regular wild-types. In summary, the males had higher rates of neuronal activity in a particular section of the SCN at midday and their genetic rhythms in the peripheral tissues peaked at different times. All in all, sex differences in the circadian system are evident and can be influenced by difference components of sexual makeup (chromosomal vs hormonal) even if the differences aren’t striking.
Kuljis, D., Loh, D., Truong, D., Vosko, A., Ong, M., McClusky, R., Arnold, A., & Colwell, C. (2013). Gonadal- and Sex-Chromosome-Dependent Sex Differences in the Circadian System Endocrinology, 154 (4), 1501-1512 DOI: 10.1210/en.2012-1921