scholarly journals Potential roles of decidual prolactin in early pregnancy

Reproduction ◽  
2001 ◽  
pp. 197-205 ◽  
Author(s):  
HN Jabbour ◽  
HO Critchley
Keyword(s):  
Early Pregnancy ◽  
Prolactin Receptor ◽  
Functional Differentiation ◽  
Trophoblast Invasion ◽  
Target Cells ◽  
Uterine Receptivity ◽  
Transmembrane Receptors ◽  
Paracrine Signalling ◽  
Successful Establishment ◽  
Decidual Prolactin

Successful establishment of pregnancy is dependent on uterine receptivity at the time of trophoblast invasion and implantation. The endometrium undergoes morphological and functional differentiation during the mid- to late secretory phase of the menstrual cycle in preparation for such an event. These changes are orchestrated by ovarian steroid hormones. However, local autocrine-paracrine signalling at the deciduo-placental interface is crucial for successful establishment of pregnancy. One key cytokine that may regulate many functions in implantation is prolactin. Prolactin is secreted by the decidualized endometrium at the time of predicted conception and, in the event of pregnancy, local expression and secretion of prolactin persists until term. Prolactin mediates its effect on target cells through interaction with single-pass transmembrane receptors. Localization of the sites of expression of the prolactin receptor indicates that the cytokine may regulate an array of functions in the pregnant uterus that are crucial in im-plantation and early pregnancy.

scholarly journals A potential molecular mechanism for regulating pre-mRNA splicing of implantation-related genes through unique uterine expression of splicing factor SC35 in women and rhesus monkeys

Reproduction ◽  
2002 ◽  
pp. 209-217 ◽  
Author(s):  
GY Nie ◽  
AL Hampton ◽  
GQ Fu ◽  
YX Liu ◽  
JK Findlay ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Rhesus Monkeys ◽  
Distinct Pattern ◽  
Oestrous Cycle ◽  
Splicing Factor ◽  
Trophoblast Invasion ◽  
Uterine Receptivity ◽  
Blastocyst Development ◽  
Specific Expression ◽  
Implantation Sites

Splicing factor SC35 is an essential component of the spliceosome, the cellular apparatus that removes introns from pre-mRNA to provide alternatively spliced isoforms. Many proteins associated with development of uterine receptivity and embryo implantation are present as isoforms, the tissue-specific expression of which may be regulated through alternative splicing. SC35 was identified as being increased at implantation sites during early pregnancy in mice. However, the present study has demonstrated that SC35 is present in human and rhesus monkey endometrium, that the protein is increased during the secretory phase of the oestrous cycle compared with the proliferative phase in both these primates and that it is present in a distinct pattern within the nucleus of both epithelial and stromal cells, as well as in cells of the vasculature. Both the intensity of immunoreactive protein and the proportion of cells that stain for SC35 alter with the phase of the oestrous cycle. A very precise expression pattern of SC35 (both protein and mRNA) was seen during early placentation in rhesus monkeys. At implantation sites between day 24 and day 35 of early pregnancy, SC35 was expressed strongly in cytotrophoblasts within the trophoblastic shell, in syncytiotrophoblast at the periphery of the cell column and in both cytotrophoblast and syncytiotrophoblast in the floating villi. In the adjacent maternal decidua, expression of SC35 was weak. These results indicate a role for SC35 in preparation of a receptive uterus, in the provision of secreted proteins to support blastocyst development and in trophoblast invasion.

scholarly journals Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Wei Hu ◽  
Yu-Xiang Liang ◽  
Jia-Mei Luo ◽  
Xiao-Wei Gu ◽  
Zi-Cong Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Early Pregnancy ◽  
Embryo Implantation ◽  
Uterine Receptivity ◽  
Positive Effects ◽  
Delayed Implantation ◽  
Nucleolar Stress ◽  
Pregnant Mice ◽  
Successful Establishment ◽  
Luminal Epithelial Cells

Abstract Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

scholarly journals Silencing SEC5 inhibits trophoblast invasion via integrin/Ca2+ signaling

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 59-71
Author(s):  
Wen-Wen Gu ◽  
Long Yang ◽  
Xing-Xing Zhen ◽  
Yan Gu ◽  
Hua Xu ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
First Trimester ◽  
Cytosolic Calcium ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Third Trimester ◽  
Imaging Results ◽  
Fetal Bovine ◽  
And Migration

The invasion of maternal decidua by extravillous trophoblast (EVT) is essential for the establishment and maintenance of pregnancy, and abnormal trophoblast invasion could lead to placenta-associated pathologies including early pregnancy loss and preeclampsia. SEC5, a component of the exocyst complex, plays important roles in cell survival and migration, but its role in early pregnancy has not been reported. Thus, the present study was performed to explore the functions of SEC5 in trophoblast cells. The results showed that SEC5 expression in human placental villi at first trimester was significantly higher than it was at the third trimester, and it was abundantly localized in the cytotrophoblast (CTB) and the trophoblastic column. SEC5 knockdown was accompanied by reduced migration and invasion in HTR-8/SVneo cells. In addition, the expression and plasma membrane distribution of integrin β1 was also decreased. Furthermore, shRNA-mediated knockdown of SEC5 inhibited the outgrowth of first trimester placental explants. SEC5 and InsP3R were colocalized in the cytoplasm of HTR-8/SVneo cells, and the cell-permeant calcium chelator BAPTA-AM could significantly inhibit HTR-8/SVneo cell invasion. The Ca2+ imaging results showed that the 10% fetal bovine serum-stimulated cytosolic calcium concentration ([Ca2+]c) was not only reduced by downregulated SEC5 but also was blocked by the InsP3R inhibitor. Furthermore, either the [Ca2+]c was buffered by BAPTA-AM or the knockdown of SEC5 disrupted HTR-8/SVneo cell F-actin stress fibers and caused cytoskeleton derangement. Taken together, our results suggest that SEC5 might be involved in regulating trophoblast cell migration and invasion through the integrin/Ca2+ signal pathway to induce cytoskeletal rearrangement.

scholarly journals DC-SIGN and L-SIGN Are Attachment Factors That Promote Infection of Target Cells by Human Metapneumovirus in the Presence or Absence of Cellular Glycosaminoglycans

2016 ◽  
Vol 90 (17) ◽  
pp. 7848-7863 ◽  
Author(s):  
Leah Gillespie ◽  
Kathleen Gerstenberg ◽  
Fernanda Ana-Sosa-Batiz ◽  
Matthew S. Parsons ◽  
Rubaiyea Farrukee ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cho Cells ◽  
Experimental System ◽  
Human Metapneumovirus ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Target Cells ◽  
Transmembrane Receptors ◽  
Hmpv Infection ◽  
Attachment Factor

ABSTRACTIt is well established that glycosaminoglycans (GAGs) function as attachment factors for human metapneumovirus (HMPV), concentrating virions at the cell surface to promote interaction with other receptors for virus entry and infection. There is increasing evidence to suggest that multiple receptors may exhibit the capacity to promote infectious entry of HMPV into host cells; however, definitive identification of specific transmembrane receptors for HMPV attachment and entry is complicated by the widespread expression of cell surface GAGs. pgsA745 Chinese hamster ovary (CHO) cells are deficient in the expression of cell surface GAGs and resistant to HMPV infection. Here, we demonstrate that the expression of the Ca2+-dependent C-type lectin receptor (CLR) DC-SIGN (CD209L) or L-SIGN (CD209L) rendered pgsA745 cells permissive to HMPV infection. Unlike infection of parental CHO cells, HMPV infection of pgsA745 cells expressing DC-SIGN or L-SIGN was dynamin dependent and inhibited by mannan but not by pretreatment with bacterial heparinase. Parental CHO cells expressing DC-SIGN/L-SIGN also showed enhanced susceptibility to dynamin-dependent HMPV infection, confirming that CLRs can promote HMPV infection in the presence or absence of GAGs. Comparison of pgsA745 cells expressing wild-type and endocytosis-defective mutants of DC-SIGN/L-SIGN indicated that the endocytic function of CLRs was not essential but could contribute to HMPV infection of GAG-deficient cells. Together, these studies confirm a role for CLRs as attachment factors and entry receptors for HMPV infection. Moreover, they define an experimental system that can be exploited to identify transmembrane receptors and entry pathways where permissivity to HMPV infection can be rescued following the expression of a single cell surface receptor.IMPORTANCEOn the surface of CHO cells, glycosaminoglycans (GAGs) function as the major attachment factor for human metapneumoviruses (HMPV), promoting dynamin-independent infection. Consistent with this, GAG-deficient pgaA745 CHO cells are resistant to HMPV. However, expression of DC-SIGN or L-SIGN rendered pgsA745 cells permissive to dynamin-dependent infection by HMPV, although the endocytic function of DC-SIGN/L-SIGN was not essential for, but could contribute to, enhanced infection. These studies provide direct evidence implicating DC-SIGN/L-SIGN as an alternate attachment factor for HMPV attachment, promoting dynamin-dependent infection via other unknown receptors in the absence of GAGs. Moreover, we describe a unique experimental system for the assessment of putative attachment and entry receptors for HMPV.

scholarly journals Human Uterine Decidual NK Cells in Women with a History of Early Pregnancy Enhance Angiogenesis and Trophoblast Invasion

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Ningyi Jia ◽  
Jian Li
Keyword(s):  
Early Pregnancy ◽  
Mrna Level ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Mrna Levels ◽  
History Of ◽  
And Migration ◽  
Primiparous Women

Objective. The present study aimed to identify changes in decidual natural killer (dNK) cells and related cytokines in women who have undergone induced abortions (IAs). The effects of dNK cells on subsequent pregnancies remain unknown. Accordingly, we sought to investigate whether a history of early pregnancy can change dNK cells and facilitate their role in the regulation of angiogenesis and trophoblast invasion. Materials and Methods. dNK cells were obtained from primiparous women who had undergone IA(s) prior to this study and primiparous women who had never been pregnant before this IA (control). Real-time polymerase chain reaction (PCR) was used to measure the mRNA levels of IFN-γ, IP-10, VEGF, and PLGF in dNK cells. The levels of these cytokines were quantified using the enzyme-linked immunosorbent assay. HUVEC and HTR-8/SVneo cells were used to evaluate the angiogenesis, migration, and invasion activities influenced by dNK cells. Results. In dNK cells, the mRNA level of IFN-γ was higher in the control group than that in the IA group. The secretion of IP-10 and VEGF was higher in the IA group compared to the control group. After coculturing with the dNK supernatant, the HTR-8/SVneo cells exhibited better invasiveness and migration in the IA group than those in the control group. Angiogenesis assay demonstrated that dNK cells from IA group might help HUVEC attain better tube formation ability. Conclusion. The findings of this study suggest that a history of early pregnancy has an impact on dNK cells. These trained dNK cells can regulate angiogenesis and trophoblast invasion and migration by promoting the production of certain cytokines.

INFLUENCE OF GLUCOSE AND INSULIN OF PROSTACYCLIN SYNTHESIS IN CULTURED TR0PH0BLAST CELLS

1987 ◽  
Author(s):  
I Rákóczi ◽  
Gy Geró ◽  
J Demeter ◽  
I Gáti
Keyword(s):  
New England ◽  
Early Pregnancy ◽  
Horse Serum ◽  
Physiological Role ◽  
First Trimester ◽  
Serum Glucose ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Specific Radioimmunoassay ◽  
High Concentrations

It is known that placental cells can produce prostacyclin /PGI2/. At present, the physiological role of trophoblast PGI2 production can only be speculative. PGI2 produced by trophoblast may help to prevent the platelet aggregation and thrombosis in spiral arteries and it can also explain the maintance of, and blood flow through, the spiral arteries during endovascular trophoblast invasion in early pregnancy. It has been previously shown that increased glucose concentrations in the incubation fluid can inhibit the formation of PGI2 by rat aortic rings. The aim of present investigation was to study the effect of glucose and insulin on the generation of PGI? by trophoblast obtained from early pregnancy. Trophoblast tissue was obtained immediately from surgical termination of first trimester pregnancy /9 specimens/. Trophoblast was cultured using the method of Jogee et al. Cells obtained from trypsinizaticn were cultured at a density of 2×105 cells/ml in medium 199 containing 10% horse,serum. Glucose /5.5, 16.5 and 33mmol/l / and insulin /103 , 104 and 106 mU/1 / were added to culture and the effect on 6-oxo-PGF2 production over a 24-hr incubation was assessed. Control cultures were incubated without glucose and insulin. The concentration of 6-oxo-PGF2 in culture supernatans were measured by specific radioimmunoassay /3H-6-oxo-PGF1, RIA-kit, New England Nuclear, USA /.There was a significant decrease in 6-keto-PGF10c production by trophoblast cells incubated with increased glucose concentrations /16.5 and 33 mmol/1 / compared to controls / p<0.001/. In contrast, insulin in growth medium did not have any effects on the PGI production. These data suggest that high concentrations of 2 glucose inhibit PGIp production by cultured trophoblast cells. This decreased PGIp synthesis may impair the blood supply of trophoblast which could play a role in the development of congenital anomalies in pregnant women with poorly controlled diabetes mellitus in the first trimester of pregnancy.

Change in distribution of cytoskeleton-associated proteins, lasp-1 and palladin, during uterine receptivity in the rat endometrium

2018 ◽  
Vol 30 (11) ◽  
pp. 1482 ◽  
Author(s):  
Leigh Nicholson ◽  
Laura Lindsay ◽  
Christopher R. Murphy
Keyword(s):  
Plasma Membrane ◽  
Focal Adhesion ◽  
Early Pregnancy ◽  
Morphological Changes ◽  
Cytoskeletal Proteins ◽  
Initial Contact ◽  
Luminal Epithelium ◽  
Uterine Receptivity ◽  
Uterine Lumen ◽  
Associated Proteins

The epithelium of the uterine lumen is the first point of contact with the blastocyst before implantation. To facilitate pregnancy, these uterine epithelial cells (UECs) undergo morphological changes specific to the receptive uterus. These changes include basal, lateral and apical alterations in the plasma membrane of UECs. This study looked at the cytoskeletal and focal adhesion-associated proteins, lasp-1 and palladin, in the uterus during early pregnancy in the rat. Two palladin isoforms, 140 kDa and 90 kDa, were analysed, with the migration-associated 140-kDa isoform increasing significantly at the time of implantation when compared with the time of fertilisation. Lasp-1 was similarly increased at this time, whilst also being located predominantly apically and laterally in the UECs, suggesting a role in the initial contact between the UECs and the blastocyst. This is the first study to investigate palladin and lasp-1 in the uterine luminal epithelium and suggests an importance for these cytoskeletal proteins in the morphological changes the UECs undergo for pregnancy to occur.

Extracellular vesicles : novel mediators of conceptus-maternal interactions in sheep

2018 ◽  
Author(s):  
◽  
Gregory W. Burns
Keyword(s):  
Extracellular Vesicles ◽  
Pregnancy Loss ◽  
Cell Types ◽  
Target Cells ◽  
Uterine Receptivity ◽  
Mediated Communication ◽  
University Of Missouri ◽  
Dynamic Component ◽  
Uterine Endometrium ◽  
Endometrial Epithelium

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Infertility and pregnancy loss are common problems affecting reproductive efficiency, health and development in livestock. Pregnancy loss occurs most commonly during the first weeks of gestation and may arise due to asynchrony between the conceptus and uterus or endometrial dysfunction, resulting in defective conceptus elongation, implantation and/or placentation. Extracellular vesicles (EVs), a term including exosomes and microvesicles, are membrane-bound nanoparticles released from diverse cell types that deliver nucleic acids and proteins to target cells. Available studies support the central hypothesis that EVs are a component of uterine histotroph and mediate crosstalk between the developing conceptus and uterine endometrium prior to implantation. Studies were conducted here to: (1) identify and characterize EVs from uterine flush of cyclic and pregnant ewes; (2) examine potential of vesicle mediated communication during early pregnancy from endometrium and elongating conceptus derived EVs; and (3) determine progesterone regulation of EV cargo, endometrial gene expression, and total EV number in the uterine lumen of cyclic sheep. Results from these studies established that: (1) EVs are a component of the uterine histotroph in sheep with pregnancy associated differences; (2) EVs emanate from the uterine endometrium and elongating conceptus; (3) the endometrial epithelium and conceptus trophectoderm uptake labeled EVs indicating a role in intercellular communication during the establishment of pregnancy; (4) uterine EV content increases more than five-fold from day 10 to 14 of the estrous cycle; (5) the endometrial epithelia produce EVs with multivesicular endosomes, the progenitors of EVs, localized to the luminal and glandular epithelium; and (6) progesterone treatment increases the number of uterine EVs and alters their miRNA cargo. Collectively, these studies have established that EVs are a dynamic component of the uterine histotroph, produced by both the uterine epithelium and conceptus trophectoderm, with the ability to traffic between maternal and embryonic tissues and support the idea that EVs mediate communication that underpins conceptus development required for the successful establishment of pregnancy. These studies provide evidence of EVs as novel mediators of communication between the developing conceptus and endometrium. Uterine EVs may provide useful biomarkers for uterine receptivity or indicate endometrial dysfunction given their dynamic cargo and robust stability in biofluids.

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