Modelling female physiology from head to Toe: Impact of sex hormones, menstrual cycle, and pregnancy

Abo, Stéphanie M C; Smith, Delaney; Stadt, Melissa

doi:10.1016/j.jtbi.2022.111074

Cited by 18 publications

(22 citation statements)

References 289 publications

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“…Additionally, pregnancy is known to alter K + regulation, leading to K + retention, to deliver sufficient K + to the rapidly developing fetus [47–50]. Female-specific mathematical models may be used to study the unique physiological state of pregnancy [51]. Another unique state of K + retention is in neonates and early childhood [52, 53].…”

Section: Discussionmentioning

confidence: 99%

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A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls

Stadt

Leete

Devinyak

2022

Preprint

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Maintaining normal potassium (K+) concentration in the extra- and intracellular fluid is critical for cell function. K+ homeostasis is achieved by ensuring proper distribution between extra- and intracellular fluid compartments and by matching K+ excretion with intake. The Na+-K+-ATPase pump facilitates K+ uptake into the skeletal muscle, where most K+ is stored. Na+-K+-ATPase activity is stimulated by insulin and aldosterone. The kidneys regulate long term K+ regulation by controlling the amount of K+ excreted through urine. Renal handling of K+ is mediated by a number of regulatory mechanisms, including an aldosterone-mediated feedback control, in which high extracellular K+ concentration stimulates aldosterone secretion which enhances urine K+ excretion, and a gastrointestinal feedforward control mechanism, in which dietary K+ intake increases K+ excretion. Recently, a muscle-kidney cross talk signal has been hypothesized, where the K+ concentration in skeletal muscle cells directly affects urine K+ excretion, without changes in extracellular K+ concentration. To understand how these mechanisms coordinate under different K+ challenges, we have developed a compartmental model of whole-body K+ regulation. The model represents the intra- and extracellular fluid compartments in a human (male) as well as a detailed kidney compartment. We included (i) the gastrointestinal feedforward control mechanism, (ii) the effect of insulin, and (iii) aldosterone on Na+-K+-ATPase K+ uptake, and (iv) aldosterone stimulation of renal K+ secretion. We used this model to investigate the impact of regulatory mechanisms on K+ homeostasis. Model predictions showed how the regulatory mechanisms synthesize to ensure that the extra- and intracellular fluid K+ concentrations remain in normal range in times of K+ loading and fasting. Additionally, we predict that without the hypothesized muscle-kidney cross talk signal, the model was unable to predict a return to normal extracellular K+ concentration after a period of high K+ loading or depletion.

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Section: Discussionmentioning

confidence: 99%

“…Female-specific mathematical models may be used to study the unique physiological state of pregnancy [51]. Another unique state of K + retention is in neonates and early childhood [52,53].…”

Section: Model Limitations and Future Workmentioning

confidence: 99%

A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls

Stadt

Leete

Devinyak

2022

Preprint

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“…Both adrenocorticotropic hormone (ACTH) and free cortisol levels have been reported to increase twice as much in men as in women in response to a psychosocial stress task, though results may depend on the specific stressor studied ( 69 ). Some studies have suggested that women's monthly hormonal fluctuations sensitize the HPA-axis ( 73 , 74 ). This may be one reason why women, more than men, risk developing stress-and-trauma-related disorders.…”

Section: Sex-based Theoriesmentioning

confidence: 99%

Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness

2022

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Sex differences are prevalent in multiple mental disorders. Internalizing disorders are more commonly diagnosed in women, whereas externalizing and neurodevelopmental disorders are more often diagnosed in men. Significant sex/gender differences are reported in prevalence, symptom profile, age of onset, comorbidities, functional impairment, prognosis, as well as in responses to various treatments. In this conceptual article, we discuss theories and empirical studies of sex- and gender-related influences in mental health, by focusing on three examples: autism spectrum disorder (ASD), acknowledged as a disorder whose roots are mainly biological; eating disorders, whose origins are considered to be mainly psychosocial, and posttraumatic stress disorder (PTSD), an environmentally caused disorder with both psychosocial and biological underpinnings. We examine the ways in which sex differences emerge, from conception through adulthood. We also examine how gender dichotomies in exposures, expectations, role assumptions, and cultural traditions impact the expression of our three selected mental illnesses. We are especially interested in how sex-based influences and gender-based influences interact with one another to affect mental illness. We suggest that sex and gender are multi-faceted and complex phenomena that result in variations, not only between men and women, but also within each sex and gender through alterations in genes, hormone levels, self-perceptions, trauma experiences, and interpersonal relationships. Finally, we propose a conceptual diatheses-stress model, depicting how sex and gender come together to result in multiple sex/gender differences across mental disorders. In our model, we categorize diatheses into several categories: biological, intrapersonal, interpersonal, and environmental. These diatheses interact with exposure to stressors, ranging from relatively minor to traumatic, which allows for the sometimes bidirectional influences of acute and long-term stress responses. Sex and gender are discussed at every level of the model, thereby providing a framework for understanding and predicting sex/gender differences in expression, prevalence and treatment response of mental disorders. We encourage more research into this important field of study.

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“…Major physiological changes happen in nearly all tissues and organs in the maternal body. 33,34 Indeed, pregnancy also affects the eyes. 35,36 Some of these changes include changes in corneal thickness and curvature as well as increases in sensation that may cause sensitivity to contact lenses.…”

Section: Pregnancymentioning

confidence: 99%

“…The parameters for Equation (33) and Equation (34) have been determined in previous model development for each of the nephron segments. 2,4…”

mentioning

confidence: 99%

From your kidneys to your eyes: lessons from computational kidney models

Stadt¹

2022

MAIO

Self Cite

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Purpose: The purpose of this review is to describe computational models that have been developed for studying kidney function and howthese models may be adapted to study the eyes. Methods: We derive equations for modeling solute andwater transport across epithelial cell membranes in the kidney. These equations describe mass conservation, as well membrane transport via cotransporters, exchangers, and primary active transport. Results: Wedescribe howcomputational models of renal transport have been applied to investigate kidney function in physiological and pathophysiological conditions. Conclusion: The computational models herein described for the kidney may be adapted to study ocular functions and dysfunction.

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Modelling female physiology from head to Toe: Impact of sex hormones, menstrual cycle, and pregnancy

Cited by 18 publications

References 289 publications

A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls

A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls

Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness

From your kidneys to your eyes: lessons from computational kidney models

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