Social Isolation Influences Endocrine and Metabolic Parameters in Female Mice Depending on Estrous State

Abstract

Social distancing is a critical public health strategy employed to reduce the transmission of respiratory illnesses, such as COVID‐19. Studies conducted throughout the pandemic suggest that social distancing measures, including staying at home, simultaneously lead to an increased experience of isolation and loneliness. Social isolation is of potential concern because previous research in both humans and non‐human animals demonstrates that reduced social interaction has detrimental effects on mental and physical wellness, including an increase in mortality rate. Despite this background, less is known about how social isolation affects physiological parameters in a comprehensive manner, especially in females. We therefore conducted this study to investigate the extent to which social isolation simultaneously impacts multiple physiological and behavioral variables related to stress, metabolism, and reproduction. To do this, we housed three‐week‐old female Swiss‐Webster mice individually or in groups of three for five weeks. We measured body weight and food consumption each week of the experiment. During the last two weeks of treatment, we tracked the estrous cycle, using vaginal cytology to determine estrous states. After four weeks of housing treatment, we used closed system respirometry to measure oxygen consumption rate as an approximation of whole‐body metabolic rate. At the conclusion of the study, we collected blood in order to measure leukocyte counts, blood glucose concentration, and serum estrogen and progesterone concentrations. Individually housed females consistently consumed more food compared to group‐housed females. While there was no effect of social isolation on the length or proportion of time spent in the different estrous phases, the effects of isolation on other physiological variables depended on estrous state. Our preliminary results suggest that body weight, oxygen consumption rate, number of large lymphocytes, blood glucose concentration, and serum progesterone concentration were higher in individually housed females in diestrus, compared to group‐housed females in diestrus. In contrast, serum estrogen concentration was lower in individually housed females in diestrus, compared to group‐housed females in diestrus. Taken together, these findings suggest that social isolation has a substantial body‐wide effect on physiology and health in females, potentially mediated through a direct effect on ovarian hormone secretion. Furthermore, these findings highlight the importance of studying how stressors impact female physiology in naturally cycling animals.