MS07 - OTHE-1
Griffin West Ballroom (#2133) in The Ohio Union

Modeling sex differences in health and disease

Thursday, July 20 at 04:00pm

SMB2023 SMB2023 Follow Thursday during the "MS07" time block.
Room assignment: Griffin West Ballroom (#2133) in The Ohio Union.
Note: this minisymposia has multiple sessions. The other session is MS06-OTHE-1 (click here).

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Melissa Stadt


Sex hormones affect most, if not all, physiological systems. Historically, most physiological and biomedical research has largely been centered around males. In recent years, more sex-specific research has been conducted, revealing key structural and morphological differences in most organ systems between the sexes. Female physiology is complicated by the varied hormone levels that occur during the menstrual cycle as well as the massive changes during pregnancy/lactation or menopause. As we move towards precision medicine, to capture our diverse population we must attain a comprehensive understanding of the effects of sex-differences as well as the varied reproductive states in females on physiological function. Mathematical models have great potential to enhance our understanding of the effects of sex and reproductive states on physiological processes. By providing a quantitative framework for simulation and hypothesis testing, mathematical modeling and analysis can help untangle the complicated interactions of sexual dimorphisms or the impacts of varied reproductive states in anatomy, sex hormones, and physiological processes. In this mini-symposium speakers will present research using mathematical modeling to understand problems in health and disease related to sex differences or women’s health.

Melissa M. Stadt

University of Waterloo (Applied Mathematics)
"Maternal calcium homeostasis: A mathematical analysis of the differential impacts of pregnancy and lactation"
Calcium plays an essential role in many physiological functions such as skeletal mineralization, muscle contractions, blood clotting, and cell signaling. While extracellular calcium makes up less than 1% of total body calcium, it is tightly regulated since too high or too low calcium levels can have dangerous effects on the body. During pregnancy and lactation, there is excess demand on the maternal body due to the needs of the fetus or milk, therefore major adaptations must occur. 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, calcium is resorbed from the bones to meet the needs of milk production. The goal of this project is to develop the first pregnancy- and lactation-specific mathematical models of calcium regulation. Model analysis reveals how both differential adaptations support the calcium demands of the fetus or milk while maintaining normal calcium ranges in the maternal body. 
Additional authors: Anita T. Layton, University of Waterloo, Department of Applied Mathematics, Cheriton School of Computer Science, Department of Pharmacy, Department of Biology

Karin Leiderman

University of North Carolina at Chapel Hill (Mathematics, Computational Medicine)
"Mathematical modeling to understand the effects of estrogen on platelet activation"
Activated platelets are essential for hemostasis and blood clotting. The activation process is a coordinated sequence of events that begins at the platelet membrane where ligands bind receptors and initiate internal signaling pathways. Estrogen has been observed to both reduce and enhance platelet responsiveness in the literature, with varying estrogen concentrations having potentially different effects. It is not yet known if these observed changes are due to estrogen receptor signaling only, or if there are other mechanisms also at play. One idea is that estrogen could induce changes in membrane properties that alter the signaling pathways leading to platelet activation. It is known that signal transduction is partially regulated by membrane properties like fluidity and lipid rafts, and that steroid hormones directly affect these types of membrane properties. We developed a mathematical model that considers both possibilities. First, it considers the downstream signaling effects that estrogen binding to estrogen receptors have on platelet activation. Second, we also assume that high levels of estrogen alter the fluidity of platelet membranes, which affects the binding dynamics of the collagen receptor, glycoprotein VI, and ultimately platelet activation. Our model qualitatively captures flow cytometry data showing similar dose response curves for platelet activation due to collagen related peptides and similar biphasic responses whereby platelet activation increases with low levels of estrogen but then decreases sharply with high estrogen levels.
Additional authors: Helen Saville, University of Cambridge; Mehrshad Sadria, University of Waterloo; Xiaoyan Deng, University of Montreal; Fatema Saghafifar, University of British Columbia; Liam Yih, University of British Columbia; Linh Huynh, University of Utah; Keith Neeves, University of Colorado Denver

Tony Humphries

McGill University (Mathematics and Statistics)
"Sex Specific Mathematical Modelling of Erythropoiesis"
The human body produces more than 10^{11} blood cells per day, in a very dynamic process which can be affected by many factors including infection, hypoxia, blood loss and donation, and exogeneous drug administration. Blood cell production takes place in the bone marrow and is difficult to observe directly, while circulating concentrations of mature blood cells are easily measured. This makes hematopoiesis an interesting target for mathematical modelling which was already recognised in the 1970s, and there has been a wealth of mathematical modelling in the last 50 years. However, this modelling almost exclusively ignores sex-specific differences. In this talk we will describe the development of a sex-specific model of erythropoiesis. As well as the need to obtain parameter values for both sexes, the sex specific modelling provides the opportunity to explore some aspects of erythropoiesis which are less well understood, including the affects of male and female sex hormones. We apply our mathematical model to several situations including modelling blood donations for both sexes, while also incorporating the menstrual cycle in the female model. This collaboration started as a project at the 2023 Modelling Sex Differences in Physiology Workshop at the Banff International Research Station.
Additional authors: Edoardo Borgiani (KU Leuven); Liang Chen (Waterloo); Suzan Farhang Sardroodi (Manitoba/U Montreal); Laurence Ketchemen Tchouaga (McGill); Melissa Stadt (Waterloo); Erin Zhao (IUPUI)

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Annual Meeting for the Society for Mathematical Biology, 2023.