Alternate roles for immune regulators: establishing endometrial receptivity for implantation

Abstract

Many immune regulators are now identified as having key roles at the embryo–maternal interface. Importantly, a cohort of cytokines, chemokines and growth factors are produced by the endometrial glands and secreted into the uterine cavity where they act both on the blastocyst and on the endometrial surface, changing adhesive capacity, modifying blastocyst development and outgrowth and providing chemoattraction, in addition to their previously known functions in immune regulation. As implantation progresses to highly controlled invasion of the trophoblast through the maternal decidua, similar factors produced by glands, decidual cells and cells of the innate immune system are critical for guiding the trophoblast to the maternal vasculature and establishing a functional placenta. Disturbance to production or action of such mediators can result in loss of uterine receptivity (manifesting as infertility) or disorders of early pregnancy including recurrent miscarriage and preeclampsia.

Keywords::

• blastocyst
• chemokine
• cytokine
• endometrium
• fertility
• implantation
• infertility
• innate immune system
• receptive endometrium
• uterine fluid

Financial & competing interests disclosure

Work in the Salamonsen Laboratory is funded by an NHMRC Program grant (#494802) and a grant from the Monash IVF Research Fund. Lois A Salamonsen is supported by an NHMRC Fellowship (#388901), Natalie J Hannan by an NHMRC Australian Postdoctoral training Fellowship (#628927) and Jemma Evans by a Lalor Foundation Fellowship. The authors also acknowledge infrastructure support from the Victorian Government’s Operational Infrastructure Support Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

NK: Natural killer.

Data taken from [124,125].