Biomaterial Database

Modeling circadian regulation of ovulation timing: age-related disruption of estrous cyclicity. 2020

Takayuki Ohara, and Takahiro J Nakamura, and Wataru Nakamura, and Isao T Tokuda

Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany. ohara@fbn-dummerstorf.de.

The circadian clocks within the hypothalamic-pituitary-gonadal axis control estrous cycles in female rodents. The suprachiasmatic nucleus (SCN), where the central clock is located, generates daily signals to trigger surge release of luteinizing hormone (LH), which in turn induces ovulation. It has been observed in aged rodents that output from the SCN such as neuronal firing activity is declined, and estrous cycles become irregular and finally stop. Circadian clock mutants display accelerated reproductive aging, suggesting the complicated interplay between the circadian system and the endocrine system. To investigate such circadian regulation of estrous cycles, we construct a mathematical model that describes dynamics of key hormones such as LH and of circadian clocks in the SCN and in the ovary, and simulate estrous cycles for various parameter values. Our simulation results demonstrate that reduction of the amplitude of the SCN signal, which is a symptom of aging, makes estrous cycles irregular. We also show that variation in the phase of the SCN signal and changes in the period of ovarian circadian clocks exacerbates the aging effect on estrous cyclicity. Our study suggests that misalignment between the SCN and ovarian circadian oscillations is one of the primary causes of the irregular estrous cycles.

UI	MeSH Term	Description	Entries
D008962	Models, Theoretical	Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.	Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010060	Ovulation	The discharge of an OVUM from a rupturing follicle in the OVARY.	Ovulations
D002940	Circadian Rhythm	The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli.	Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D056950	Period Circadian Proteins	Circadian rhythm signaling proteins that influence circadian clock by interacting with other circadian regulatory proteins and transporting them into the CELL NUCLEUS.	Circadian Clock Protein Period,Circadian Clock Protein Period 1,Circadian Clock Protein Period 2,Circadian Clock Protein Period 3,Circadian Pacemaker Protein Rigui,Period Circadian Protein 1,Period Circadian Protein 2,Period Circadian Protein 3,Period Proteins
D057906	Circadian Clocks	Biological mechanism that controls CIRCADIAN RHYTHM. Circadian clocks exist in the simplest form in cyanobacteria and as more complex systems in fungi, plants, and animals. In humans the system includes photoresponsive RETINAL GANGLION CELLS and the SUPRACHIASMATIC NUCLEUS that acts as the central oscillator.	Circadian Clock System,Circadian Timing System,Circadian Clock,Circadian Clock Systems,Circadian Timing Systems,Clock System, Circadian,Clock Systems, Circadian,Clock, Circadian,Clocks, Circadian,System, Circadian Clock,System, Circadian Timing,Systems, Circadian Clock,Systems, Circadian Timing,Timing System, Circadian,Timing Systems, Circadian
D030762	Estrous Cycle	The period of cyclic physiological and behavior changes in non-primate female mammals that exhibit ESTRUS. The estrous cycle generally consists of 4 or 5 distinct periods corresponding to the endocrine status (PROESTRUS; ESTRUS; METESTRUS; DIESTRUS; and ANESTRUS).	Cycle, Estrous,Cycles, Estrous,Estrous Cycles