Human Endometrial Transcriptomics: Implications for Embryonic Implantation

Abstract

Human endometrium has been extensively investigated in the search for markers capable of predicting its receptive status. The completion of the Human Genome Project has triggered a rapid development of new fields in molecular biology, the "transcriptomics" being a major turning point in the knowledge acquisition of endometrial receptivity. Based on this, a customized Endometrial Receptivity Array (ERA) has been developed, which is capable of identifying the genomic signature of receptivity. This diagnostic tool showed that the window of implantation (WOI) is displaced in one out of four patients with implantation failure, allowing the identification of their personalized WOI. This strategy allows performing a personalized embryo transfer ( pET) on the day in which the endometrium is receptive. The combination of a systems biology approach and next-generation sequencing will overcome the limitations of microarrays, and will, in the future, allow elucidation of the mechanisms involved in embryo implantation.T he endometrium, which lines the inside of the uterine cavity, undergoes cyclic changes that are regulated by ovarian steroids. It can be subdivided into the basal layer that is responsible for its regenerative capacity, and the functional layer that undergoes proliferation, secretion, and tissue degeneration every month from menarche to menopause. Its aim is to prepare the optimal moment for embryonic implantation known as the window of implantation (WOI).The endometrial cycle comprises the menstrual, proliferative, and secretory phases. The proliferative phase, which corresponds to the ovarian follicular phase and increased production of estrogens, lasts until ovulation occurs. During this stage, the increasing estrogen levels cause the proliferation of the stromal cells as well as the elongation of the spiral arteries. After ovulation, with the appearance of progesterone secreted by the granulosa-luteal cells, the secretory phase begins. If implantation does not occur, the secretory phase ends, and the corpus luteum degenerates. Menstruation occurs owing to the drop of estrogen and progesterone, which resets the endometrium until pregnancy

ATP mediates the interaction between human blastocyst and endometrium

“…Impaired embryo implantation and decidualization results in pregnancy loss and infertility and may be the main cause of the lower implantation rate in assistive reproductive technology . Given the pervasiveness of this problem, many efforts have been made to study the receptivity of the endometrium for the blastocyst . However, the molecular mechanism underlying the crosstalk between the embryo and endometrium remains unclear.…”

“…4,5 Given the pervasiveness of this problem, many efforts have been made to study the receptivity of the endometrium for the blastocyst. 6,7 However, the molecular mechanism underlying the crosstalk between the embryo and endometrium remains unclear.…”

Embryo implantation evolved from an ancestral inflammatory attachment reaction

“…Furthermore, decades of research have failed to produce clinically effective treatments that increase uterine receptivity to implantation (6)(7)(8). Given the magnitude of this problem, extensive efforts have been made to characterize the endometrium for signatures of receptivity (9,10).…”

Intrauterine infusion of human chorionic gonadotropin before embryo transfer in IVF/ET cycle: The critical review

“…13,44,65,66,124 Using these "diagnostic" methods, potential candidates for IUI-hCG can be selected and therapeutic effect can be More importantly, all the reported studies that conducted this intervention were based on the population characteristics (ie implantation failure, infertile), but not on etiological indications (ie the number of NK cells, or expression of cytokines).…”

“…Recently, transcriptomic endometrial analysis has been introduced as a potential diagnostic approach to determine the window of implantation. 13 However, therapeutic options for the results of these tests are fairly limited to improve endometrial receptivity.…”