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

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.

Grant, Azure D., Linda Wilbrecht, and Lance J. Kriegsfeld,  Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Semi-Naturalistic Conditions, Journal of Biological Rhythms, (May 2022). https://doi.org/10.1177/07487304221092715

Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Semi-Naturalistic Conditions2022-06-18T20:34:48+00:00

Adolescent Development of Biological Rhythms: Estradiol Dependence and Effects of Combined Contraceptives

Purpose Adolescence is a period of continuous development, including the maturation of endogenous rhythms across systems and timescales. Although these dynamic changes are well recognized, their continuous structure and hormonal dependence have not been systematically characterized. Given the well-established link between core body temperature (CBT) and reproductive hormones in adults, we hypothesized that high-resolution CBT can be applied to passively monitor pubertal development and disruption with high fidelity.

Methods To examine this possibility, we used signal processing to investigate the trajectory of CBT rhythms at the within-day (ultradian), daily (circadian), and ovulatory timescales, their dependence on estradiol, and the effects of hormonal contraceptives.

Results Puberty onset was marked by a rise in fecal estradiol (fE2), followed by an elevation in CBT and circadian power. This time period marked the commencement of 4-day rhythmicity in fE2, CBT, and ultradian power marking the onset of the estrous cycle. The rise in circadian amplitude was accelerated by E2 treatment, indicating a role for this hormone in rhythmic development. Contraceptive administration in later adolescence reduced CBT and circadian power and resulted in disruption to 4-day cycles that persisted after discontinuation.

Conclusions Our data reveal with precise temporal resolution how biological rhythms change across adolescence and demonstrate a role for E2 in the emergence and preservation of multiscale rhythmicity. These findings also demonstrate how hormones delivered exogenously in a non-rhythmic pattern can disrupt rhythmic development. These data lay the groundwork for a future in which temperature metrics provide an inexpensive, convenient method for monitoring pubertal maturation and support the development of hormone therapies that better mimic and support human chronobiology.

Azure D. Grant, Linda Wilbrecht, Lance J. Kriegsfeld, Adolescent Development of Biological Rhythms: Estradiol Dependence and Effects of Combined Contraceptives, Frontiers in Physiology, Nov. 5, 2021, https://www.frontiersin.org/articles/10.3389/fphys.2021.752363/full

Adolescent Development of Biological Rhythms: Estradiol Dependence and Effects of Combined Contraceptives2022-06-18T14:39:17+00:00