Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Semi-naturalistic Conditions

Abstract

Biological rhythms in core body temperature (CBT) provide informative markers of adolescent development under controlled laboratory conditions. However, it is unknown whether these markers are preserved under more variable, semi-naturalistic conditions, and whether CBT may therefore prove useful in a real-world setting. To evaluate this possibility, we examined fecal steroid concentrations and CBT rhythms from pre-adolescence (p26) through early adulthood (p76) in intact male and female Wistar rats under natural light and climate at the Stephen Glickman Field Station for the Study of Behavior, Ecology and Reproduction. Despite greater environmental variability, CBT markers of pubertal onset and its rhythmic progression were comparable with those previously reported in laboratory conditions in female rats and extend actigraphy-based findings in males. Specifically, sex differences emerged in CBT circadian rhythm (CR) power and amplitude prior to pubertal onset and persisted into early adulthood, with females exhibiting elevated CBT and decreased CR power compared with males. Within-day (ultradian rhythm [UR]) patterns also exhibited a pronounced sex difference associated with estrous cyclicity. Pubertal onset, defined by vaginal opening, preputial separation, and sex steroid concentrations, occurred later than previously reported under lab conditions for both sexes. Vaginal opening and increased fecal estradiol concentrations were closely tied to the commencement of 4-day oscillations in CBT and UR power. By contrast, preputial separation and the first rise in testosterone concentration were not associated with adolescent changes to CBT rhythms in male rats. Together, males and females exhibited unique temporal patterning of CBT and sex steroids across pubertal development, with tractable associations between hormonal concentrations, external development, and temporal structure in females. The preservation of these features outside the laboratory supports CBT as a strong candidate for translational pubertal monitoring under semi-naturalistic conditions in females.

Crosstalk between circadian clocks and pathogen niche

“…These changes are multi-oscillatory and follow seasonal, ovulatory, and circadian cycles and are mediated through both the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes, where communication is bidirectional [119][120][121]. Importantly, sex differences can contribute to variance of rhythms, for instance, in body temperature [122] and pubertal development [123], which should encourage inclusion of sex as a biological variable in circadian experiments.…”

Neural substrates underlying rhythmic coupling of female reproductive and thermoregulatory circuits

“…Conversely, their pattern of activity can be rescued, in part, by phytoestrogen-rich food (e.g., black cohosh) and by direct estradiol replacement ( Opas et al, 2004 ; Hui et al, 2012 ). Notably, although temperature level is commonly reduced by these interventions, effects on ultradian temperature patterning are more variable, suggesting that tonic administration of estrogens can impact temperature setpoint and ultradian patterning differentially ( Opas et al, 2004 ; Grant et al, 2022 ). It is likely that temporal patterns of sex-steroid receptor expression are altered at hormone-responsive thermoregulatory loci, leading to changes in ultradian patterning, a possibility requiring further investigation.…”