Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles

Abstract

Embryo–endometrial communication plays a critical role in embryo implantation and the establishment of a successful pregnancy. Successful pregnancy outcomes involve maternal immune modulation during embryo implantation. The endometrium is usually primed and immunomodulated by steroid hormones and embryo signals for subsequent embryo implantation and the maintenance of pregnancy. The roles of extracellular vesicles (EVs) and microRNAs for the embryo–maternal interactions have been elucidated recently. New evidence shows that endometrial EVs and trophectoderm-originated EV cargo, including microRNAs, proteins, and lipids in the physiological microenvironment, regulate maternal immunomodulation for embryo implantation and subsequent pregnancy. On the other hand, trophoblast-derived EVs also control the cross-communication between the trophoblasts and immune cells. The exploration of EV functions and mechanisms in the processes of embryo implantation and pregnancy will shed light on a practical tool for the diagnostic or therapeutic approaches to reproductive medicine and infertility.

The Premetastatic Lymph Node Niche in Gynecologic Cancer

“…These data will add valuable information to the recently expanding field of gynecological oncoimmunology. Immunotherapy can now be used in microsatellite-unstable endometrial cancer patients regardless of the PD-L1 status and in cervical cancer patients in association with the PD-L1 status, while the important role of the immune microenvironment is constantly expanding in several gynecological conditions [ 19 , 20 , 21 , 22 ].…”

Preterm birth, a consequence of immune deviation mediated hyperinflammation

“…A healthy full-term pregnancy represents a notably feat, as it presents a formidable challenge to the maternal immune system. Extensive reviews have underscored that the maternal immune response commences as early as sperm entry into the vagina [ 21 , [23] , [24] , [25] ], marking the onset of an intricate journey characterized by immune activation, tolerance, and subsequent reactivation ( Fig. 1 ).…”

A Lifelong Impact on Endometriosis: Pathophysiology and Pharmacological Treatment

“…Alterations of the intrafollicular microenvironment and aberrant steroidogenesis impair folliculogenesis and oocyte competence [ 118 , 119 ]. Dysregulation of immune and inflammatory profiles plays an essential role in recurrent implantation failure and early pregnancy loss [ 49 , 120 , 121 ]. Adenomyosis, characterized by the defective junctional zone and perturbed uterine peristalsis, is strongly associated with primary infertility and adverse in vitro fertilization (IVF) outcomes [ 122 , 123 ].…”