Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond

PROBLEM: The peri-conceptual environment influences the early embryo to impart long-term consequences for the fetus and neonate; however, the underlying mechanisms are not well defined. METHOD OF STUDY: We argue that the cytokine network acting in the female reproductive tract during the pre- and peri-implantation period integrates environmental information to program the embryo and fine-tune the maternal immune response and endometrial remodelling to determine implantation success. RESULTS: As well as sex steroid hormones and male seminal fluid factors, female tract cytokines are influenced by agents signalling via the Toll-like receptors including the microbiome and a plethora of metabolic, chemical and other stressors. In mouse models, an altered peri-conceptual cytokine environment induced by cytokine deficiency, inflammatory insults or dysregulated seminal fluid signalling is associated with adverse effects on embryo development, pregnancy viability and reproductive outcome. CONCLUSION: The cytokine network provides a pivotal mechanism through which environmental factors influence both embryo development and receptivity of the uterus.