Of mice and (wo)men: factors influencing successful implantation including endocannabinoids

Abstract

BACKGROUND One in six couples suffer from infertility problems requiring in vitro fertilization therapy; however, the average birth rates in the past decade per IVF-embryo transfer cycle have remained static at around 25%. Although implantation failure is considered a major cause of infertility in otherwise healthy women, inadequate uterine receptivity is considered to be responsible for only two-thirds of implantation failures and problems with the embryo itself are responsible for the other third, such that only 30% of oocytes that are contacted by sperm result in successful human term pregnancies. Due to technical and ethical considerations, most research into the factors affecting the success of embryo implantation has been performed in mice, but this may be less than ideal. METHODS Selected relevant literature detailing the similarities and differences between rodent and human reproductive physiology surrounding implantation were nominated for inclusion. Primary papers and review articles (and primary sources within these), published between 1975 and 2012, with a clear indication for a particular ligand or cell being involved in the implantation process or placentation in the mouse or woman, were thoroughly examined and used to construct the review. RESULTS Mice have been identified as suitable models for investigating the processes of early pregnancy in women, for many reasons including their predictable, relatively short gestation and the ability to deliberately breed mice with the absence of a desired gene. There is, however, increasing evidence to suggest that the reproductive systems of humans and mice differ considerably when considering early pregnancy events. CONCLUSIONS In this review, we examine what is already known about the normal implantation process and the intrinsic factors that affect implantation, and then compare the differences between mice models and women in the context of early pregnancy. We highlight numerous differences between the mice and women and conclude it is becoming clear that all of the data from mouse studies cannot be confidently extrapolated to human reproduction.

Endometrial pinopode biomarkers: Molecules and microRNAs

“…Several studies have shown that integrin αvβ3 is involved in decidualization; also, it is a potential receptor for blastocyst attachment and plays a role in the initial stage of adhesion that depend on pinopode. Therefore, αvβ3 integrin can be used for the detection of pinopode‐formation sites (Melford et al, ; Thouas et al, ). Some studies have reported that αvβ3 integrin and pinopodes are two major markers of the implantation window (Cai, Li, & He, ).…”

“…Previous studies have shown that small interfering RNA that suppress MEIS1 affect maturation of pinopodes and expression of integrin β3, and reduce the average implantation rate (L. Hu, Li, et al, ). However, rates without HOXA10 and LIF express pinopode (Melford et al, ).…”

Endocannabinoids

“…Interestingly, circulating lymphocytes also play a critical role in human embryo implantation. The addition of AEA to human lymphocytes in vitro inhibits the release of leukemia inhibitor factor (LIF), further highlighting the tight interaction between the many processes that support early pregnancy Melford et al 2014). Taken together, it is apparent that eCB signaling plays a key role in all the early phases of embryo development, in order to ensure a proper pregnancy outcome.…”

Expression, regulation and function of Egr1 during implantation and decidualization in mice

“…5 Thus implantation failure is considered a major cause of infertility in healthy women. 3,6 For the couples undergoing in vitro fertilization and embryo transfer cycles, implantation rates remain disappointingly low, probably owing to non-synchronization of blastocyst activation with uterine receptivity. [2][3][4] Although molecular and genetic evidences have provided valuable insights into the mechanisms of implantation with respect to ovarian hormones, cytokines, growth factors, adhesion molecules and transcription factors, there is limited information regarding the nature of implantation.…”