Blastocyst-endometrium interaction: intertwining a cytokine network

Abstract

The successful implantation of the blastocyst depends on adequate interactions between the embryo and the uterus. The development of the embryo begins with the fertilized ovum, a single totipotent cell which undergoes mitosis and gives rise to a multicellular structure named blastocyst. At the same time, increasing concentrations of ovarian steroid hormones initiate a complex signaling cascade that stimulates the differentiation of endometrial stromal cells to decidual cells, preparing the uterus to lodge the embryo. Studies in humans and in other mammals have shown that cytokines and growth factors are produced by the pre-implantation embryo and cells of the reproductive tract; however, the interactions between these factors that converge for successful implantation are not well understood. This review focuses on the actions of interleukin-1, leukemia inhibitory factor, epidermal growth factor, heparin-binding epidermal growth factor, and vascular endothelial growth factor, and on the network of their interactions leading to early embryo development, peri-implantatory endometrial changes, embryo implantation and trophoblast differentiation. We also propose therapeutical approaches based on current knowledge on cytokine interactions.

Platelet concentrate in bovine reproduction: effects on in vitro embryo production and after intrauterine administration in repeat breeder cows

“…Studies in humans and in other mammals have shown that cytokines and growth factors are produced by the pre-implantation embryo and cells of the reproductive tract, even if the exact combinations required for successful implantation are not yet fully understood [23]. Based on the current knowledge of the regenerative effect of PC due to its high growth factor and cytokine content [22], this study proposes a novel therapeutic approach.…”

“…In this context, the uterine administration of PC may be useful in peri-implantation, or in the healing process of clinically silent endometrial injuries because many cytokines act as intermediary links in the materno-fetal relationship including decidualization (in the women), implantation, placentation, embryogenesis and fetal growth [23]. Moreover, since pro-inflammatory factor transcripts in bovine endometrial epithelial cells are elevated in case of subclinical or clinical endometritis [24], we hypothesized that an early administration of PC, after artificial insemination (AI) and before the descent of the blastocyst in the uterus, could improve the uterine microenvironment for embryo implantation and counteract eventual subclinical endometritis.…”

Microvesicles secreted from equine amniotic-derived cells and their potential role in reducing inflammation in endometrial cells in an in-vitro model

“…Repeat-breeding cows (animals that after three or more inseminations do not get pregnant because of fertilization failure or early embryonic death) show abnormalities in the growth factor-cytokine network, specifically in endometrial epidermal growth factor (EGF) concentration [12]. The EGF family acts on the trophectoderm, promoting cell attachment and embryo development [13], and its impairment could explain the pregnancy failure in these animals.…”

Study on teratogenic effects of methotrexate; Alteration of gene expression pattern in human placenta choriocarcinoma (JEG-3) cells

“…A successful pregnancy requires normal embryo implantation and placentation. In this complex developmental process, the proliferation of trophoblast cells is one of the critical events [21][22][23][24][25][26][27] .…”

“…Scatter plot analysis was made by Microsoft Excel 2000 (Microsoft, USA). Significance Analysis of Microarray (SAM) was performed for the selection of the genes with significant gene expression changes 25 . The statistical significant differentially expressed genes were assessed by computing a q-value for each gene.…”