The maternal womb

Abstract

The dramatic rise in worldwide prevalence of obesity has necessitated the search for more efficacious anti-obesity strategies to counter the increased cancer risks in overweight and obese individuals. The mechanistic pathways linking obesity status with adult chronic diseases such as cancer remain incompletely understood. A growing body of evidence suggests that novel approaches and interventional agents to disrupt the feed-forward cycle of maternal to offspring obesity transfer that is initiated in utero, will be important for stemming both the obesity pandemic and the associated increase in cancer incidence. The convergence of multiple research areas including those encompassing the insulin and insulin-like growth factor (IGF) systems, epigenetics, and stem cell biology is providing insights into the potential for cancer prevention in adult offspring previously exposed to the intrauterine environment of overweight/obese mothers. Here, we review the current state of this nascent research field, with a focus on three major cancers namely breast, colorectal and liver, and suggest some possible future directions to optimize its impact for the health of future generations.

Maternal pre-pregnancy and gestational diabetes, obesity, gestational weight gain, and risk of cancer in young children: a population-based study in California

“…Consequently, though pre-pregnancy and gestational diabetes both result in maternal hyperglycemia, their impact on fetal development is dependent on the management of these conditions [51]. Maternal hyperglycemia increases fetal growth, alters fetal metabolism, and induces oxidative stress and epigenetic changes [28, 52, 53]. The pathways linking maternal diabetes to childhood cancer risk are not fully understood, but the associations we observed are likely explained by a combination of these factors, which may explain why we did not find a consistently higher risk for all childhood cancers that have been associated with accelerated fetal growth.…”

Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice

“…Indeed, studies in mouse models have demonstrated causality between maternal obesity and offspring’s compromised cardiovascular health and increased cancer risks (Blackmore HL et al , 2014; Simmen & Simmen, 2011). While consumption of a high-fat diet does not necessarily result in obesity, there is a growing consensus that maternal dietary intake of high-fat mimicking a typical ‘Western diet’, similar to maternal obesity, elicits metabolic dysfunctions in progeny through early changes in metabolome due in part to deregulated insulin signaling (Cox et al , 2009; Montales et al , 2014; Vogt et al , 2014).…”

“…Moreover, increasing evidence supports a possible link between metabolic syndrome and breast cancer (Simmen & Simmen, 2011; Hauner & Hauner, 2014). A recent study from our group (Montales et al , 2014) provided a proof of this concept by using the Wnt1-Transgenic (Tg) mouse model of human breast cancer (Li et al , 2000).…”

Effects of obesity on hormonally driven cancer in women

“…All the current data suggest that maternal obesity is linked to other cancer outcomes through secondary mechanisms. For example, a recent review proposed that maternal obesity influences obesity and weight gain in offspring and therefore predisposes offspring to colorectal cancer (30). This is founded on the observation that obesity of the patient at diagnosis and weight gain in adult life are risk factors for colorectal cancer (30).…”