Connecting Female Infertility to Obesity, Inflammation, and Maternal Gut Dysbiosis.

Abstract

The prevalence of obesity has reached alarming proportions globally, and continues to rise in both developed and developing countries. At least 2.8 million people each year die as a result of being overweight or obese. According to the estimates by the World Health Organization in 2008 more than 1.4 billion adults were overweight in 2008, and more than half a billion were obese, and the number of overweight and obese adults is projected to increase to 2.2 billion and 1.1 billion, respectively, by 2030. As the numbers of obese women increases the associated comorbidities like type 2 diabetes, coronary heart disease, cancers and reproductive disorders will also increase. Women with obesity have a number of reproductive disorders including problems with ovulation, decreased rates of conception, infertility, early pregnancy loss, birth defects, and reduced assisted reproductive technology success (1, 2). The increased incidence of miscarriages and assisted reproductive technology failure in obese women (3, 4) is attributed in large part to poor oocyte quality manifest as impaired oocyte maturation and disrupted spindle morphology. A number of investigators provide evidence of metabolic perturbations in oocytes from obese mothers including high levels of intracellular lipid (5), elevated endoplasmic reticulum (6), and oxidative stress (7, 8), increased accumulation of oocyte mRNA (9), and mitochondrial dysfunction (1, 7). These obesity-induced alterations in ovarian follicle development and oocyte quality are associated with activation of systemic or local inflammatory pathways (10–12). In this issue of Endocrinology, Xie et al (13) find that obesity-dependent increases in proinflammatory signaling regulates the abundance of oocyte specific mRNAs (Figure 1). This journey began when this group found that a subset of maternal RNAs, including maternal effect genes, are elevated in oocytes from mature obese mice (9) and women with metabolic dysfunction (14). These observations are important because the increased abundance of maternal effect genes is known to interfere with normal embryonic development (15, 16). In the present study, to induce the obese phenotype the investigators fed young adult female mice normal rodent chow or a high-fat diet containing 45% or 60% of its calories from fat. The highfat diet induced increases in adipose tissue and whole body