Glycosylation changes during differentiation of the murine uterine epithelium

2001 ◽  
Vol 29 (2) ◽  
pp. 156-162 ◽  
Author(s):  
S. J. Kimber ◽  
R. E. Stones ◽  
S. S. Sidhu

In mouse uterine luminal epithelium (LE) several terminal carbohydrate structures are regulated by ovarian steroids and show stage-specific expression during early pregnancy. We have demonstrated that expression of H-type-1 antigen (Fucα1-2Galβ1-3GlcNAcβ1-) is regulated by oestrogenic stimulation of α-2fucosyltransferase (fut1) mRNA levels in LE. H-type-1 expression is high after ovulation but becomes negligible after implantation. In contrast, NeuNAcα2-3Galβ1-, and specifically sialyl Le-x (NeuAcα2,3Galβ1,4-[Fucα1-3]GlcNAcβ1-), is stimulated by progesterone. It is not expressed on LE after ovulation but is expressed maximally on apical LE at the time of and after implantation. However, mRNA levels for 4 out of 5 known Gal/GalNAc α2-3sialyltransferases appear not to change in LE during early pregnancy, suggesting an alternative level of control.

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 437
Author(s):  
Ting Gong ◽  
Weiyong Wang ◽  
Houqiang Xu ◽  
Yi Yang ◽  
Xiang Chen ◽  
...  

Testicular expression of taste receptor type 1 subunit 3 (T1R3), a sweet/umami taste receptor, has been implicated in spermatogenesis and steroidogenesis in mice. We explored the role of testicular T1R3 in porcine postnatal development using the Congjiang Xiang pig, a rare Chinese miniature pig breed. Based on testicular weights, morphology, and testosterone levels, four key developmental stages were identified in the pig at postnatal days 15–180 (prepuberty: 30 day; early puberty: 60 day; late puberty: 90 day; sexual maturity: 120 day). During development, testicular T1R3 exhibited stage-dependent and cell-specific expression patterns. In particular, T1R3 levels increased significantly from prepuberty to puberty (p < 0.05), and expression remained high until sexual maturity (p < 0.05), similar to results for phospholipase Cβ2 (PLCβ2). The strong expressions of T1R3/PLCβ2 were observed at the cytoplasm of elongating/elongated spermatids and Leydig cells. In the eight-stage cycle of the seminiferous epithelium in pigs, T1R3/PLCβ2 levels were higher in the spermatogenic epithelium at stages II–VI than at the other stages, and the strong expressions were detected in elongating/elongated spermatids and residual bodies. The message RNA (mRNA) levels of taste receptor type 1 subunit 1 (T1R1) in the testis showed a similar trend to levels of T1R3. These data indicate a possible role of T1R3 in the regulation of spermatid differentiation and Leydig cell function.


2000 ◽  
Vol 165 (2) ◽  
pp. 231-243 ◽  
Author(s):  
RS Robinson ◽  
GE Mann ◽  
TS Gadd ◽  
GE Lamming ◽  
DC Wathes

The IGF system is expressed in the uterus during the oestrous cycle and early pregnancy and is likely to play an important role in regulating the development of the embryo and uterus. The IGF peptides (IGF-I and -II) mediate their effects through the type 1 IGF receptor (IGF-1R), while the IGF-binding proteins (IGFBP-1 to -6) modulate their interaction with the receptor. In this study, the expression of the IGF system in the bovine uterus was determined throughout the oestrous cycle and on day 16 of pregnancy. Endometrial biopsy samples were collected from four cows over three cycles such that there were samples for every 2 days from day 0 (oestrus) to day 14 and then every day until day 21. To assess the effect of pregnancy, uterine horn cross-sections were collected on day 16 from 15 pregnant (PREG), five inseminated non-pregnant (INP) and nine uninseminated cyclic controls (CONT). The expression of mRNA for the IGFs, IGF-1R and IGFBP-1 to -5 was determined by in situ hybridisation and the results were quantified by measuring the optical density units from autoradiographs. The main region of IGF-I mRNA expression was the sub-epithelial stroma underlying the luminal epithelium. The expression of IGF-I mRNA was highest at oestrus and lowest during the early and late luteal phases. On day 16, IGF-I mRNA levels were low in all groups, with pregnancy having no effect on the IGF-I mRNA concentrations. The strongest expression of IGF-II mRNA was in the caruncular stroma, with pregnancy having no significant effect in this region. IGF-1R mRNA was also present in the caruncles and was strongly expressed in all epithelial cells both throughout the oestrous cycle and during early pregnancy. The expression of IGFBP-1 mRNA was confined to the luminal epithelium, with the strongest expression seen on day 14 of the cycle. On day 16 the expression of IGFBP-1 mRNA was higher in the PREG group compared with the CONT group. The expression of IGFBP-2 mRNA was localised to the sub-epithelial stroma with more INP than PREG cows showing detectable levels of IGFBP-2. The strongest expression of IGFBP-3 mRNA was in the caruncular stroma; expression in the endometrial stroma was similarly decreased during early pregnancy. IGFBP-5 mRNA was mainly expressed in the inner ring of myometrium and was not affected by pregnancy on day 16. In conclusion, these results show that many components of the uterine IGF system are differentially regulated during the oestrous cycle and early pregnancy and suggest that modulation of the IGF system may influence uterine activity during this period.


1993 ◽  
Vol 265 (4) ◽  
pp. C1046-C1049 ◽  
Author(s):  
M. K. Raizada ◽  
B. Rydzewski ◽  
D. Lu ◽  
C. Sumners

Angiotensin II (ANG II) stimulates plasminogen activator inhibitor 1 (PAI-1) gene expression in astroglial cells prepared from rat brains. In this study, we investigated whether c-fos gene expression may be involved in this cellular action of ANG II. Incubation of astroglial cultures with ANG II caused a time- and dose-dependent transient stimulation of the steady-state levels of c-fos mRNA, with a maximal stimulation of 50-fold observed with 100 nM ANG II within 30-45 min. This stimulation was completely abolished by the presence of the type 1 ANG II (AT1) receptor antagonist losartan but not by the type 2 ANG II receptor blocker PD-123177. Depolarization of brain cell cultures with 50 mM K+ also caused a 100-fold increase in c-fos mRNA levels, an effect partially blocked by losartan. These observations show that AT1 receptor activation stimulates expression of the c-fos gene, which may act as a third messenger in the regulation of cellular actions of ANG II, including PAI-1 gene expression in astroglial cells.


1998 ◽  
Vol 142 (1) ◽  
pp. 217-227 ◽  
Author(s):  
Di Lu ◽  
Hong Yang ◽  
Robert H. Lenox ◽  
Mohan K. Raizada

Angiotensin II (Ang II) exerts chronic stimulatory actions on tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), and the norepinephrine transporter (NET), in part, by influencing the transcription of their genes. These neuromodulatory actions of Ang II involve Ras-Raf-MAP kinase signal transduction pathways (Lu, D., H. Yang, and M.K. Raizada. 1997. J. Cell Biol. 135:1609–1617). In this study, we present evidence to demonstrate participation of another signaling pathway in these neuronal actions of Ang II. It involves activation of protein kinase C (PKC)β subtype and phosphorylation and redistribution of myristoylated alanine-rich C kinase substrate (MARCKS) in neurites. Ang II caused a dramatic redistribution of MARCKS from neuronal varicosities to neurites. This was accompanied by a time-dependent stimulation of its phosphorylation, that was mediated by the angiotensin type 1 receptor subtype (AT1). Incubation of neurons with PKCβ subtype specific antisense oligonucleotide (AON) significantly attenuated both redistribution and phosphorylation of MARCKS. Furthermore, depletion of MARCKS by MARCKS-AON treatment of neurons resulted in a significant decrease in Ang II–stimulated accumulation of TH and DβH immunoreactivities and [3H]NE uptake activity in synaptosomes. In contrast, mRNA levels of TH, DβH, and NET were not influenced by MARKS-AON treatment. MARCKS pep148–165, which contains PKC phosphorylation sites, inhibited Ang II stimulation of MARCKS phosphorylation and reduced the amount of TH, DβH, and [3H]NE uptake in neuronal synaptosomes. These observations demonstrate that phosphorylation of MARCKS by PKCβ and its redistribution from varicosities to neurites is important in Ang II–induced synaptic accumulation of TH, DβH, and NE. They suggest that a coordinated stimulation of transcription of TH, DβH, and NET, mediated by Ras-Raf-MAP kinase followed by their transport mediated by PKCβ-MARCKS pathway are key in persistent stimulation of Ang II's neuromodulatory actions.


2019 ◽  
Vol 20 (1) ◽  
pp. 75-84

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy


2021 ◽  
pp. 1-10
Author(s):  
Ericka Greene ◽  
Jason Thonhoff ◽  
Blessy S. John ◽  
David B. Rosenfield ◽  
Santosh A. Helekar

Background: Repeated neuromuscular electrical stimulation in type 1 Myotonic Dystrophy (DM1) has previously been shown to cause an increase in strength and a decrease in hyperexcitability of the tibialis anterior muscle. Objective: In this proof-of-principle study our objective was to test the hypothesis that noninvasive repetitive transcranial magnetic stimulation of the primary motor cortex (M1) with a new portable wearable multifocal stimulator causes improvement in muscle function in DM1 patients. Methods: We performed repetitive stimulation of M1, localized by magnetic resonance imaging, with a newly developed Transcranial Rotating Permanent Magnet Stimulator (TRPMS). Using a randomized within-patient placebo-controlled double-blind TRPMS protocol, we performed unilateral active stimulation along with contralateral sham stimulation every weekday for two weeks in 6 adults. Methods for evaluation of muscle function involved electromyography (EMG), hand dynamometry and clinical assessment using the Medical Research Council scale. Results: All participants tolerated the treatment well. While there were no significant changes clinically, EMG showed significant improvement in nerve stimulus-evoked compound muscle action potential amplitude of the first dorsal interosseous muscle and a similar but non-significant trend in the trapezius muscle, after a short exercise test, with active but not sham stimulation. Conclusions: We conclude that two-week repeated multifocal cortical stimulation with a new wearable transcranial magnetic stimulator can be safely conducted in DM1 patients to investigate potential improvement of muscle strength and activity. The results obtained, if confirmed and extended by future safety and efficacy trials with larger patient samples, could offer a potential supportive TRPMS treatment in DM1.


2021 ◽  
Vol 22 (15) ◽  
pp. 7932
Author(s):  
Sourav Panja ◽  
John T. Benjamin ◽  
Bibhash C. Paria

Maternal infection-induced early pregnancy complications arise from perturbation of the immune environment at the uterine early blastocyst implantation site (EBIS), yet the underlying mechanisms remain unclear. Here, we demonstrated in a mouse model that the progression of normal pregnancy from days 4 to 6 induced steady migration of leukocytes away from the uterine decidual stromal zone (DSZ) that surrounds the implanted blastocyst. Uterine macrophages were found to be CD206+ M2-polarized. While monocytes were nearly absent in the DSZ, DSZ cells were found to express monocyte marker protein Ly6C. Systemic endotoxic lipopolysaccharide (LPS) exposure on day 5 of pregnancy led to: (1) rapid (at 2 h) induction of neutrophil chemoattractants that promoted huge neutrophil infiltrations at the EBISs by 24 h; (2) rapid (at 2 h) elevation of mRNA levels of MyD88, but not Trif, modulated cytokines at the EBISs; and (3) dose-dependent EBIS defects by day 7 of pregnancy. Yet, elimination of maternal neutrophils using anti-Ly6G antibody prior to LPS exposure failed to avert LPS-induced EBIS defects allowing us to suggest that activation of Tlr4-MyD88 dependent inflammatory pathway is involved in LPS-induced defects at EBISs. Thus, blocking the activation of the Tlr4-MyD88 signaling pathway may be an interesting approach to prevent infection-induced pathology at EBISs.


2017 ◽  
Vol 95 (4) ◽  
pp. 382-387 ◽  
Author(s):  
Mariam Shiri ◽  
Alireza Komaki ◽  
Shahrbanoo Oryan ◽  
Masoumeh Taheri ◽  
Hamidreza Komaki ◽  
...  

Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212–2, (3) capsaicin, and (4) WIN55,212–2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212–2, a cannabinoid receptor (CB1/CB2) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212–2 (CB1/CB2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212–2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats’ cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212–2 on learning and memory.


2002 ◽  
Vol 76 (22) ◽  
pp. 11570-11583 ◽  
Author(s):  
Brian R. Lane ◽  
Jianguo Liu ◽  
Paul J. Bock ◽  
Dominique Schols ◽  
Michael J. Coffey ◽  
...  

ABSTRACT The development of the complex neoplasm Kaposi's sarcoma is dependent on infection with the Kaposi's sarcoma-associated herpesvirus (KSHV) and appears to be greatly enhanced by cytokines and human immunodeficiency virus type 1 (HIV-1) Tat. Interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-α) are chemokines involved in chemoattraction, neovascularization, and stimulation of HIV-1 replication. We have previously demonstrated that production of GRO-α is stimulated by exposure of monocyte-derived macrophages (MDM) to HIV-1. Here we show that exposure of MDM to HIV-1, viral Tat, or viral gp120 leads to a substantial increase in IL-8 production. We also demonstrate that IL-8 and GRO-α are induced by KSHV infection of endothelial cells and are crucial to the angiogenic phenotype developed by KSHV-infected endothelial cells in cell culture and upon implantation into SCID mice. Thus, the three known etiological factors in Kaposi's sarcoma pathogenesis—KSHV, HIV-1 Tat, and cellular growth factors—might be linked, in part, through induction of IL-8 and GRO-α.


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