The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

The kidneys contribute to glucose homeostasis by gluconeogenesis and glucose reabsorption. Herein, we identified previously unknown fasting-induced, glucagon-mediated inhibitory effect of the circadian clock gene basic helix-loop-helix ARNT like 1 (Bmal1) on the expression of the main proximal tubule glucose transporter solute carrier family 5 member 2 (Sglt2) in mice. During fasting, glucagon induces Bmal1, which increases expression of nuclear receptor subfamily 1, group D, member 1 (Rev-erbα). Rev-erbα represses nuclear respiratory factor 1, a transcriptional activator of Sglt2, and diminishes Sglt2 expression and thereby kidney glucose reabsorption capacity. During refeeding (lower glucagon) this process is attenuated, thereby inducing glucose reabsorption. The physiological role of this mechanism appears to ensure optimal temporal retrieval of filtered glucose during fasting/refeeding. Thus, this study demonstrates that during fasting and refeeding, glucagon regulates renal glucose reabsorption by utilizing the local cellular circadian machinery.

Background: Alzheimer’s Disease (AD) incidence is almost double in women, suggesting sex‐specific risk genes for AD remain to be uncovered.Method: To identify AD risk genes in smaller cohorts of only male or only female subjects we designed a machine learning case‐control study of genome variant differences that included a functional importance score as a feature. The method robustly finds genes in smaller cohorts, enabling us to analyze men and women separately.Result: We found AD‐associated risk genes men‐only, women‐only, or combined subjects. These genes were consistent with a) prior AD GWAS; b) expression in AD patients brain regions; c) transcriptome analyses; d) and in vivo experiments in fly models of Amyloid beta and Tau neurodegeneration. Notably, the sex‐specific genes implicate pathways that are differentially altered in each sex – a stress response pathway unique to AD affected men and cell‐cycle/DNA quality control pathways unique to AD affected women.Conclusion: A machine learning combined with an evolution‐based training feature for variant impact identified common as well as sex‐specific AD‐associated genes and mechanisms of potential value for pre‐symptomatic risk assessment and drug targeting.