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

Abstract

Citation Robertson SA, Chin PY, Glynn DJ, Thompson JG. Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond. Am J Reprod Immunol 2011; 66 (Suppl. 1): 2–10Problem 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.

Female Tract Cytokines and Developmental Programming in Embryos

“…We argue that maternal tract cytokines are well-suited to provide a pathway through which inflammatory, infectious and chemical insults can converge and integrate, since all of these factors alter cytokine expression in the reproductive tract (Robertson et al 2011). We predict that cytokines operate together with availability of nutrients (amino acids, pyruvate, lactate, hexose sugars and lipids) and physiochemical parameters including oxygen, ionic composition and ammonia (Thompson et al 2005) to provide the signals through which embryos sense the prevailing environment and adjust their developmental program accordingly.…”

Human Trophoblast Cells Modulate Endometrial Cells Nuclear Factor κB Response to Flagellin In Vitro

“…Uterine receptivity to the embryo is clearly influenced by the hormones, growth factors and cytokines present in the uterine environment during the window of implantation. This cytokine network is extremely sensitive to systemic and local changes and needs to be kept in balance for a successful implantation [6], [7]. One of the main regulators of the immune response is the Toll-like receptor family (TLR).…”

The actors of human implantation: gametes, embryo and endometrium

“…Implantation failure would come from an inadequate gamete/embryo quality, an erroneous cross-talk at the implantation site or an inadequate peri-conceptual environment. As recently demonstrated by Robertson et al, the peri-conceptual period and environment are critical for pregnancy success: the local cytokine network of the reproductive tract integrates environmental information and provides a signaling system programming both maternal receptivity and embryo development (Robertson et al, 2011). On the other hand, data from Kashiwagi (Kashiwagi et al, 2007) and from Bauersachs (Bauersachs et al, 2009) evidence that both embryo and endometrium are closely related and are actively influenced by each other, in order to favor pregnancy or, at contrary, to reject it.…”

“…Despite extensive research in this field, the implantation process remains the black box of the reproduction, even in 2012. An important wastage of embryos is observed since the majority of blastocysts will perish before or around implantation (Macklon et al, 2002;Robertson et al, 2011;Teklenburg et al, 2010a). Implantation failure would come from an inadequate gamete/embryo quality, an erroneous cross-talk at the implantation site or an inadequate peri-conceptual environment.…”