Inflammatory Bowel Disease: Influence and Implications in Reproduction

Abstract

The incidence and prevalence of inflammatory bowel disease (IBD) continues to rise with time, signifying its emergence as a global disease. Clinical onset of IBD, comprising Crohn's disease and ulcerative colitis, typically occurs before or at peak reproductive age. Although active disease in female patients is associated with reduced fertility and adverse obstetric outcomes in pregnancy, the molecular mechanisms underlying this altered reproductive course, and its impact on IBD transmission to offspring, remain poorly understood. Clinical and experimental studies have now begun to elucidate the hormonal, environmental, and microbial factors that modulate immune-reproductive cross talk in IBD and define their impact on maternal health, fetal development, and heritability of disease risk. Evolving insight into maternal-fetal imprinting in IBD has important implications for patient counseling and disease management during pregnancy and may help predict clinical outcomes for both mother and child.

Figure 1

IBD, pregnancy and maternal disease transmission. Active IBD during pregnancy increases the risk of adverse obstetric outcomes. Maternal IBD-associated factors that are thought to contribute to this risk include vitamin D deficiency and overproduction of proinflammatory mediators such as TNF. Evidence from mouse models indicates that maternal environment markedly impacts fetal immune and metabolic development, fetal epigenomic programming and gut colonization, and fetal exposure to maternal microbes or microbial components likely shapes mucosal immune development and tolerance. Symptomatic maternal disease during pregnancy may therefore also influence the life-long IBD susceptibility of offspring. Conversely, pregnancy-elicited hormonal surges and placental-derived immunomodulatory pregnancy glycoproteins can modulate disease though altered immune and barrier cell function.