Predictors and consequences of maternal-origin microchimerism: A study of women in the Philippines

Abstract

Microchimerism (Mc) refers to the presence of a small number of cells or DNA from a genetically distinct individual. This phenomenon occurs naturally with bidirectional maternal-fetal exchange during pregnancy, and Mc can persist for decades after delivery. Past research on Mc has largely focused on the long term health of mothers and immune disorders that affect young children. However, each life stage (gestation, infancy, childhood, adolescence, and adulthood) faces different tradeoffs in immune function. This dissertation leverages data from a multigenerational, longitudinal health study and introduces Mc as a mediating factor in immune tradeoffs throughout the life course. Mc is thought to influence host immune function by: 1) directly contributing stem cells that differentiate and develop into functional immune cells and 2) expressing foreign antigens that trigger host immune system responses. However, there are considerable gaps in our understanding of the basic biology of Mc, including what determines why some individuals have more Mc than others and how these differences might impact reproductive fitness. This dissertation attempts to fill these gaps by reporting investigations with the following specific aims: 1) evaluate predictors of maternal-origin Mc in young adult women, 2) assess whether Mc is associated with lower risk of early life infection, and 3) determine whether adult women with Mc from their mothers have lower risk of adverse pregnancy outcomes when they have offspring of their own. Results indicate that participants who were breastfed as infants have diminished maternal-origin Mc compared to those who were never breastfed. There was no evidence of a relationship between Mc and early life infection or third generation offspring birth weight, but financial and technological limitations may have obscured my ability to detect the true relationship.