Obesity associated advanced glycation end products within the human uterine cavity adversely impact endometrial function and embryo implantation competence.

STUDY QUESTION: Do obese levels of advanced glycation end products (AGEs) within the uterine cavity detrimentally alter tissue function in embryo implantation and placental development? SUMMARY ANSWER: Obese levels of AGEs activate inflammatory signaling (p65 NF?B) within endometrial epithelial cells and alter their function, cause endoplasmic reticulum (ER) stress in endometrial stromal cells and impair decidualization, compromise implantation of blastocyst mimics and inhibit trophoblast invasion. WHAT IS KNOWN ALREADY: Obese women experience a higher incidence of infertility, recurrent miscarriage and pregnancy complications compared with lean women. Oocyte donation cycles suggest a detrimental uterine environment plays a role in these outcomes. STUDY DESIGN, SIZE, DURATION: Uterine lavage and tissues from lean (BMI 19.524.9, n = 17) and obese (BMI > 30, n = 16) women examined. Cell culture experiments utilizing human endometrial epithelial, trophectoderm and trophoblast cell lines and primary human stromal cells used to examine the functional impact of obese levels of AGEs. PARTICIPANTS/MATERIALS, SETTING, METHODS: Levels of AGEs examined within uterine lavage assessed by ELISA to determine differences between lean and obese women. Expression and localization of AGEs, receptor for AGEs (RAGE) and NF?B within endometrial tissues obtained from lean and obese women determined by immunohistochemistry. Endometrial epithelial cells (ECC-1), primary human stromal cells and trophoblast cells (HTR8-SVneo) treated with lean (2000 nmol/mol lysine) or obese (8000 nmol/mol lysine) uterine levels of AGEs and p65 NF?B (western immunoblot), real-time adhesion, proliferation migration and invasion (xCelligence real-time cell function analysis), decidualization (cell morphology and prolactin release), ER stress (western immunoblot for p-PERK) determined. Co-cultures of endometrial epithelial cells and blastocyst mimics (trophectoderm spheroids) similarly treated with lean or obese