Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity

Paiva, Premila; Hannan, Natalie J.; Hincks, C.; Meehan, Katie; Pruysers, Enid; Dimitriadis, Evdokia; Salamonsen, Lois A.

doi:10.1093/humrep/der027

Cited by 135 publications

(84 citation statements)

References 57 publications

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“…During the implantation process, the blastocyst regulates the expression and secretion of integrins β3, α4 and α1 (Simón et al, 1997), the interleukin-1 (IL-1) system (De los Santos et al, 1996), chemokines IL-8, MCP-1 and RANTES (CaballeroCampo et al, 2002), leptin (Cervero et al, 2004;González et al, 2000) and hCG (Licht et al, 2001;Paiva et al, 2011) by the endometrial epithelium during the window of implantation (WOI), the period when the endometrium is receptive to a blastocyst. The EF, a viscous fluid secreted by the endometrial glands into the uterine cavity, nurtures the embryo and constitutes the microenvironment in which the first bidirectional dialogue between the maternal endometrium and the embryo occurs during the WOI (Cha et al, 2012(Cha et al, , 2013Thouas et al, 2014;Tranguch et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome

et al. 2015

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During embryo implantation, the blastocyst interacts with and regulates the endometrium, and endometrial fluid secreted by the endometrial epithelium nurtures the embryo. Here, we propose that maternal microRNAs (miRNAs) might act as transcriptomic modifier of the pre-implantation embryo. Microarray profiling revealed that six of 27 specific, maternal miRNAs were differentially expressed in the human endometrial epithelium during the window of implantation -a brief phase of endometrial receptivity to the blastocyst -and were released into the endometrial fluid. Further investigation revealed that hsa-miR-30d, the expression levels of which were most significantly upregulated, was secreted as an exosome-associated molecule. Exosome-associated and free hsa-miR-30d was internalized by mouse embryos via the trophectoderm, resulting in an indirect overexpression of genes encoding for certain molecules involved in the murine embryonic adhesion phenomenon -Itgb3, Itga7 and Cdh5. Indeed, this finding was supported by evidence in vitro: treating murine embryos with miR-30d resulted in a notable increase in embryo adhesion. Our results suggest a model in which maternal endometrial miRNAs act as transcriptomic modifiers of the preimplantation embryo.

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Section: Introductionmentioning

confidence: 99%

Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome

et al. 2015

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“…Finally, EVTs infiltrate into decidual spiral arteries to remodel the vessel walls (Chen et al 2012). The entire process is precisely regulated by modulators at the maternal-fetal interface; for example, decidual immune cells (DICs), DSCs, female steroid hormones and cytokines (Paiva et al 2011, Oreshkova et al 2012. However, failure to achieve this process may result in pregnant complications, such as abortion, preeclampsia, fetal growth restriction (FGR), gestational trophoblastic diseases, and so on (Kwak-Kim et al 2010, Kinoshita et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through ERK1/2 and PI3K signaling pathways in human early pregnancy

Meng

Shang

et al. 2015

Reproduction

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Chemokine CCL24, acting through receptor CCR3, is a potent chemoattractant for eosinophil in allergic diseases and parasitic infections. We recently reported that CCL24 and CCR3 are co-expressed by trophoblasts in human early pregnant uterus. Here we prove with evidence that steroid hormones estradiol (E), progesterone (P), and human chorionic gonadotropin (hCG), as well as decidual stromal cells (DSCs) could regulate the expression of CCL24 and CCR3 of trophoblasts. We further investigate how trophoblast-derived CCL24 mediates the function of trophoblasts in vitro, and conclude that CCL24/CCR3 promotes the proliferation, viability and invasiveness of trophoblasts. In addition, analysis of the downstream signaling pathways of CCL24/CCR3 show that extracellular signal-regulated kinases (ERK1/2) and phosphoinositide 3-kinase (PI3K) pathways may contribute to the proliferation, viability and invasiveness of trophoblasts by activating intracellular molecules Ki67 and matrix metallopeptidase 9 (MMP9). However, we did not observe any inhibitory effect on trophoblasts when blocking c-Jun N-terminal kinase (JNK) or p38 pathways. In conclusion, our data suggests that trophoblast-derived CCL24 at the maternal-fetal interface promotes trophoblasts cell growth and invasiveness by ERK1/2 and PI3K pathways. Meanwhile, pregnancy-related hormones (P and hCG), as well as DSCs could up-regulate CCL24/CCR3 expression in trophoblasts, which may indirectly influence the biological functions of trophoblasts. Thus, our results provide a possible explanation for the growth and invasion of trophoblasts in human embryo implantation. Reproduction (2015) 150 417-427

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“…An effect of hCG on the endometrium was clearly demonstrated in an elegant in vivo study in which hCG was infused into the uterine cavity of women in the mid-secretory phase and found to induce production of pro-implantation factors: leukaemia inhibitory factor (LIF) and vascular endothelial growth factor (VEGF) [22], observations reinforced by studies in non-human primates [23]. In vitro, hCG stimulates secretion of selected cytokines by endometrial epithelial cells, confirming LIF and VEGF as hCG targets but also identifying IL-11, FGF2, GM-CSF and CXCL10 and prokineticin 1 as novel hCG-induced factors [24,25]. Since all of these have known pro-implantation functions, it is clear that during a conception cycle, blastocyst-derived hCG acts to enhance endometrial receptivity.…”

Section: Blastocyst-derived Human Chorionic Gonadotrophin Enhances Rementioning

confidence: 93%

Assessing Receptivity of the Human Endometrium to Improve Outcomes of Fertility Treatment

Edgell

Evans

Rombauts

et al. 2016

Uterine Endometrial Function

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Despite considerable improvements in assessment of embryo quality in infertility clinics, outcomes in terms of take-home baby rate have not improved substantially. Failure of the endometrium to achieve receptivity and the timing of the receptive period are now recognised as important issues in the success of IVF. Indeed, immunohistochemical and morphological studies show that the endometrium is highly disturbed in any cycle in which ovulation induction is performed, leading to recommendations that all embryos be frozen and replaced in a non-stimulation cycle. Assessment of any woman for endometrial receptivity either in cycles prior to treatment or testing for the potential for an embryo to implant in the cycle of transfer is urgently needed. However, careful consideration must be given to issues such as sampling, timing and rapid delivery of results as well as the best biomarkers, to enable in-clinic decision-making. Here these issues are

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Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity

Abstract: These findings clearly support roles for hCG and FGF2 in the blastocyst-endometrial cross-talk important for endometrial receptivity and blastocyst implantation.

Cited by 135 publications

References 57 publications

Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome

Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome

Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through ERK1/2 and PI3K signaling pathways in human early pregnancy

Assessing Receptivity of the Human Endometrium to Improve Outcomes of Fertility Treatment

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