BMS seminar at CSRL: Advanced Glycation End Products: a new player in obesity related infertility, Jennifer Hutchinson, Hudson Institute of Medical Research, Australia
Abstract: Obesity is a global pandemic: In England, 64% of the population is overweight or obese, critically ~30% of women of reproductive age are obese (NHS Digital). Obesity reduces both natural and IVF pregnancy success, and increases miscarriage & preeclampsia risk. ‘Toxic’ Advanced Glycation End-Products (AGEs), formed when reducing sugars react with the free amino group on proteins, a spontaneous process which happens endogenously within the body, and also during food preparation. AGEs are four-fold elevated in the uterine cavity of obese, infertile women versus lean. AGEs equimolar to the obese uterine cavity negatively impact the development of the preimplantation embryo. When exposed to elevated AGEs, fewer blastocysts hatch from the zona pellucida, a critical step to allow embryo adhesion and implantation to the maternal endometrium. By day five of development, these embryos also have fewer trophectoderm cells- critical for adhesion, implantation, and ultimately placentation- and exhibit reduced implantation competence. Furthermore, the maternal endometrium is significantly affected by elevated AGEs, with all cell types showing compromised functions. Obesity related AGEs provide a critical link between obesity and reduced fertility, and preconception reduction of these AGEs may improve fertility outcomes for these women.