Melissa Stadt | Applied Mathematics, University of Waterloo
Mathematical modelling of calcium homeostasis: Impact of sex, pregnancy, and lactation
Calcium is an essential electrolyte that plays a role in many biological functions such as skeletal mineralization, muscle contractions, blood clotting, and cell signalling. While extracellular calcium makes up less than 1% of total body calcium, it is tightly regulated since too high or too low extracellular calcium concentration can have dangerous effects on the body. Given the multitude of physiological processes involved in calcium regulation, its study well-suited for investigation via mathematical modelling. While mathematical models have been developed to study calcium homeostasis in males, none have been used to fully investigate known sex differences in hormone levels nor the unique physiological states of pregnancy and lactation. Calcitriol, the active form of vitamin D, plays a key role in intestinal calcium absorption, renal calcium reabsorption, and bone remodeling. It has been shown that when compared to age-matched rats, females have significantly lower calcitriol levels than males. In this study we first seek to investigate the impact of this difference as well as other known sex differences on calcium homeostasis using mathematical modelling. Despite having a similar additional calcium demand, maternal adaptations in pregnancy and lactation differ. During pregnancy, intestinal absorption of calcium is massively increased in the mother’s body to meet the needs of the developing fetus. However, during lactation, intestinal absorption returns to normal levels and the calcium needs of breastmilk are met by increased bone resorption and renal calcium reabsorption. Given these observations, the goal of this project is to develop the first sex-, pregnancy-, and lactation-specific mathematical models of calcium regulation. The resulting models represent (1) how sex-differences impact calcium homeostasis in females vs. males and (2) how a female body adapts to support the excess demands brought on by pregnancy and lactation.