Global players with local impact: Novel biomarkers for fertility

Worldwide, over 48.5 million couples are experiencing infertility and, given the obesity pandemic, this number is expected to further increase. Patients attending fertility clinics are often overweight, characteristic that have been associated with lower success rates of natural and assisted reproduction. Oocytes from overweight/obese women are frequently of lower quality and number, and this may be due to an altered composition of the natural environment of the oocyte, the ovarian follicular fluid (FF). FF is a mix of locally produced and blood-derived components, and changes in its composition impact oocyte development. Interestingly, increasing BMI alters FF composition indirectly by inducing changes in systemic metabolism. Therefore, female metabolic health likely influences oocyte quality via FF. Nonetheless, the relationship between systemic metabolism, FF composition and oocyte quality has been insufficiently investigated. Therefore, the present thesis examined the presence of three novel, “global” players in systemic metabolism in human FF: bile acids (crucial in fat digestion and glucose, lipid and energy metabolism), high density lipoprotein (HDL) function (main carrier of cholesterol in FF; in cardiology, HDL has been shown to have anti-oxidative and anti-inflammatory properties) and trimethylamine-N-oxide (TMAO, produced by the gut bacteria and emerging as a player in cardiometabolic disease). These components are present in FF and likely originate from blood. Importantly, the bile acid ursodeoxycholic acid, HDL anti-inflammatory function and TMAO are related to embryo quality and may server as novel biomarkers for fertility. In the future, targeting these components of blood and FF through lifestyle interventions may help decrease infertility.