Uterine Receptivity is Reflected by LIF Expression in the Cervix

Author(s):  
Yamato Fukui ◽  
Yasushi Hirota ◽  
Shizu Aikawa ◽  
Chihiro Ishizawa ◽  
Rei Iida ◽  
...  
Keyword(s):  
1967 ◽  
Vol 56 (3_Suppla) ◽  
pp. S7-S45 ◽  

ABSTRACT Autoradiographic, enzymic and histologic studies on uteri of pregnant rats were carried out to follow the endometrial modifications which take place during progestation (days L0 – L4) and culminate in the state of uterine receptivity essential for ovum-implantation. Pulse labelling with tritiated thymidine (radioactive DNA precursor) on L0, L1 and L2 revealed a sequence of cell renewal in luminal and glandular epithelium and endometrial stroma. On L3 and L4 stromal cells showed extensive incorporation of tritiated thymidine. This synthetic activity was associated with endometrial preparation for decidualization and was evoked at least in part, by the surge of oestrogen on L3. All layers of the uterine wall were heavily infiltrated on L0 and resembled the site of an acute inflammatory reaction. Subsequently, polymorphonuclear infiltration diminished and monocytic cells predominated. On L3 a spatial arrangement was observed: eosinophiles were concentrated in the basal endometrium and monocytic cells in the subepithelial stroma. A comparison was made between such a shift in migratory cells in the uterus and similar phenomena which occur in inflammatory and immune reactions. Activities of acid and alkaline phosphatases, of ATP-ase and succinic dehydrogenase were low on L0 and L1 during the periods of infiltration, degeneration and regeneration of luminal and glandular epithelium. Enzymic activities increased on the following days, (L3 and L4). Vascular dilation and engorgement and endometrial oedema were observed near the blastocysts on L4. Most blastocysts incorporated tritiated thymidine after 14.00 h on L4, but some showed uptake before loss of the zona which occurs usually between 14.00 and 16.00 h; therefore, it was assumed that the permeability of the zona increases prior to being shed. Activities of succinic dehydrogenase and acid and alkaline phosphatases were demonstrable in blastocysts on L4 while they were still »free« in the uterine lumen.


2012 ◽  
Vol 24 (1) ◽  
pp. 68 ◽  
Author(s):  
Olivier Sandra ◽  
Nadéra Mansouri-Attia ◽  
Richard G. Lea

Successful pregnancy depends on complex biological processes that are regulated temporally and spatially throughout gestation. The molecular basis of these processes have been examined in relation to gamete quality, early blastocyst development and placental function, and data have been generated showing perturbations of these developmental stages by environmental insults or embryo biotechnologies. The developmental period falling between the entry of the blastocyst into the uterine cavity to implantation has also been examined in terms of the biological function of the endometrium. Indeed several mechanisms underlying uterine receptivity, controlled by maternal factors, and the maternal recognition of pregnancy, requiring conceptus-produced signals, have been clarified. Nevertheless, recent data based on experimental perturbations have unveiled unexpected biological properties of the endometrium (sensor/driver) that make this tissue a dynamic and reactive entity. Persistent or transient modifications in organisation and functionality of the endometrium can dramatically affect pre-implantation embryo trajectory through epigenetic alterations with lasting consequences on later stages of pregnancy, including placentation, fetal development, pregnancy outcome and post-natal health. Developing diagnostic and prognostic tools based on endometrial factors may enable the assessment of maternal reproductive capacity and/or the developmental potential of the embryo, particularly when assisted reproductive technologies are applied.


Endocrinology ◽  
2017 ◽  
Vol 158 (4) ◽  
pp. 979-992 ◽  
Author(s):  
Diana Monsivais ◽  
Caterina Clementi ◽  
Jia Peng ◽  
Paul T. Fullerton ◽  
Renata Prunskaite-Hyyryläinen ◽  
...  
Keyword(s):  

Endocrinology ◽  
2018 ◽  
Vol 159 (6) ◽  
pp. 2459-2472 ◽  
Author(s):  
Yan Yin ◽  
Adam Wang ◽  
Li Feng ◽  
Yu Wang ◽  
Hong Zhang ◽  
...  

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.


2008 ◽  
Vol 79 (6) ◽  
pp. 1169-1175 ◽  
Author(s):  
Manyu Li ◽  
Yongqin Wu ◽  
Kathleen M. Caron
Keyword(s):  

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 319-331 ◽  
Author(s):  
Stefan Bauersachs ◽  
Susanne E Ulbrich ◽  
Karin Gross ◽  
Susanne E M Schmidt ◽  
Heinrich H D Meyer ◽  
...  

The endometrium plays a central role among the reproductive tissues in the context of early embryo–maternal communication and pregnancy. This study investigated transcriptome profiles of endometrium samples from day 18 pregnant vs non-pregnant heifers to get insight into the molecular mechanisms involved in conditioning the endometrium for embryo attachment and implantation. Using a combination of subtracted cDNA libraries and cDNA array hybridisation, 109 mRNAs with at least twofold higher abundance in endometrium of pregnant animals and 70 mRNAs with higher levels in the control group were identified. Among the mRNAs with higher abundance in pregnant animals, at least 41 are already described as induced by interferons. In addition, transcript levels of many new candidate genes involved in the regulation of transcription, cell adhesion, modulation of the maternal immune system and endometrial remodelling were found to be increased. The different expression level was confirmed with real-time PCR for nine genes. Localisation of mRNA expression in the endometrium was shown byin situhybridisation forAGRN,LGALS3BP,LGALS9,USP18,PARP12andBST2. A comparison with similar studies in humans, mice, and revealed species-specific and common molecular markers of uterine receptivity.


Author(s):  
Sudikshya Paudel ◽  
Bangmin Liu ◽  
Magdalina J Cummings ◽  
Kelsey E Quinn ◽  
Fuller W Bazer ◽  
...  

Abstract Adrenomedullin (ADM) is an evolutionarily conserved multi-functional peptide hormone that regulates implantation, embryo spacing and placentation in humans and rodents. However, the potential roles of ADM in implantation and placentation in pigs, as a litter-bearing species, are not known. This study determined abundances of ADM in uterine luminal fluid, and the patterns of expression of ADM and its receptor components (CALCRL, RAMP2, RAMP3, and ACKR3) in uteri from cyclic and pregnant gilts, as well as conceptuses (embryonic/fetus and its extra-embryonic membranes) during the peri-implantation period of pregnancy. Total recoverable ADM was greater in the uterine fluid of pregnant compared with cyclic gilts between Days 10 and 16 post-estrus, and was from uterine luminal epithelial (LE) and conceptus trophectoderm (Tr) cells. Uterine expression of CALCRL, RAMP2, and ACKR3 were affected by day (P < 0.05), pregnant status (P < 0.01) and/or day x status (P < 0.05). Within porcine conceptuses, expression of CALCRL, RAMP2 and ACKR3 increased between Days 10 and 16 of pregnancy. Using an established porcine trophectoderm (pTr1) cell line, it was determined that 10−7 M ADM stimulated proliferation of pTr1 cells (P < 0.05) at 48 h, and increased phosphorylated mechanistic target of rapamycin (p-MTOR) and 4E binding protein 1 (p-4EBP1) by 6.1- and 4.9-fold (P < 0.0001), respectively. These novel results indicate a significant role for ADM in uterine receptivity for implantation and conceptus growth and development in pigs. They also provide a framework for future studies of ADM signaling to affect proliferation and migration of Tr cells, spacing of blastocysts, implantation and placentation in pigs.


Endocrinology ◽  
2019 ◽  
Vol 161 (1) ◽  
Author(s):  
Arin K Oestreich ◽  
Sangappa B Chadchan ◽  
Pooja Popli ◽  
Alexandra Medvedeva ◽  
Marina N Rowen ◽  
...  

Abstract Uterine receptivity is critical for establishing and maintaining pregnancy. For the endometrium to become receptive, stromal cells must differentiate into decidual cells capable of secreting factors necessary for embryo survival and placental development. Although there are multiple reports of autophagy induction correlated with endometrial stromal cell (ESC) decidualization, the role of autophagy in decidualization has remained elusive. To determine the role of autophagy in decidualization, we utilized 2 genetic models carrying mutations to the autophagy gene Atg16L1. Although the hypomorphic Atg16L1 mouse was fertile and displayed proper decidualization, conditional knockout in the reproductive tract of female mice reduced fertility by decreasing the implantation rate. In the absence of Atg16L1, ESCs failed to properly decidualize and fewer blastocysts were able to implant. Additionally, small interfering RNA knock down of Atg16L1 was detrimental to the decidualization response of human ESCs. We conclude that Atg16L1 is necessary for decidualization, implantation, and overall fertility in mice. Furthermore, considering its requirement for human endometrial decidualization, these data suggest Atg16L1 may be a potential mediator of implantation success in women.


Sign in / Sign up

Export Citation Format

Share Document