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1.
Arch Gynecol Obstet ; 307(6): 1795-1809, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35708783

RESUMEN

PURPOSE: Events in the uterus during the peri-implantation period include embryo development, acquisition of uterine receptivity, implantation and decidualization. Hippo signaling pathway regulates cell proliferation, apoptosis and differentiation. We aimed to determine localization and expressions of pYAP (Phospho Yes-associated protein), YAP (Yes-associated protein), TEAD1 (TEA domain family member 1) and CTGF (Connective tissue growth factor), members of the Hippo signaling pathway, in the mouse uterus during the peri-implantation period. METHODS: Pregnant mice were randomly separated into 5 groups: 1st, 4th, 5th, 6th, and 8th days of pregnancy groups. Non-pregnant female mice in estrous phase were included in the estrous group. Uteri and implantation sites were collected. Also, inter-implantation sites were collected from the 5th day of pregnancy group. pYAP, YAP, TEAD-1 and CTGF were detected by immunohistochemistry and Western blotting. RESULTS: We observed that the expressions of YAP, TEAD-1 and CTGF were increased in the luminal and glandular epithelium on the 1st and 4th days of pregnancy when epithelial proliferation occurred. pYAP expression was high, and YAP and CTGF expressions were low in the luminal epithelium of the implantation sites on the 5th day of pregnancy, when epithelial differentiation occurred. pYAP expression was low, YAP and CTGF expressions were high at implantation sites on the 6th and 8th days of pregnancy, where decidua was formed. CONCLUSION: Our findings suggest that the Hippo signaling pathway might be involved in implantation and decidualization. Our findings will guide further studies and may help to elucidate underlying causes of implantation failure and pregnancy loss.


Asunto(s)
Vía de Señalización Hippo , Proteínas Señalizadoras YAP , Embarazo , Femenino , Ratones , Animales , Implantación del Embrión/fisiología , Útero/fisiología , Desarrollo Embrionario
2.
J Assist Reprod Genet ; 38(9): 2349-2361, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33993396

RESUMEN

PURPOSE: Implantation is essential for a successful pregnancy. Despite the increasing number of studies, implantation is still an unknown process. This study aimed to determine whether sirtuin-1 has a role in embryo implantation in oxidative stress-induced mice. METHODS: Pregnant mice were separated into 5 groups: control, vehicle, paraquat, SRT1720, and SRT1720+Paraquat. Paraquat is a herbicide and is used to induce oxidative stress. SRT1720 is a specific sirtuin-1 activator. Implantation and inter-implantation sites were removed in the morning of the 5th day of pregnancy after Chicago blue injection was performed. Sirtuin-1 and Forkhead box O1 (FoxO1) were detected by immunohistochemistry and Western blot while acetylated lysine was evaluated by Western blot analysis. Reactive oxygen and nitrogen species (ROS/RNS) and superoxide dismutase (SOD) activity were determined by fluorometric and spectrometric methods, respectively. RESULTS: Although there was no embryo implantation in paraquat-treated mice, 5 out of 9 SRT1720+Paraquat-treated mice had implantation sites which were significantly higher compared to the paraquat-treated group. Sirtuin-1 and FoxO1 expressions were increased at implantation sites of SRT1720-treated mice. ROS/RNS levels were decreased, while deacetylated FoxO1 levels and SOD activity were increased in SRT1720-treated mice. CONCLUSION: Our findings suggest that sirtuin-1 may play a role in embryo implantation against oxidative stress through FoxO1-SOD signaling.


Asunto(s)
Implantación del Embrión/fisiología , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Estrés Oxidativo , Paraquat/toxicidad , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo , Animales , Implantación del Embrión/efectos de los fármacos , Femenino , Herbicidas/toxicidad , Ratones , Ratones Endogámicos BALB C , Embarazo , Sirtuina 1/química , Sirtuina 1/genética
3.
Histochem Cell Biol ; 152(6): 423-437, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31630211

RESUMEN

Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C-8C) and sham groups (5S-8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.


Asunto(s)
Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Antagonistas de Hormonas/farmacología , Oocitos/efectos de los fármacos , Pubertad/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Animales , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona Liberadora de Gonadotropina/química , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/farmacología , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/química , Ratones , Ratones Endogámicos BALB C , Oocitos/metabolismo , Pubertad/metabolismo
4.
Int Braz J Urol ; 44(5): 1014-1022, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30044599

RESUMEN

OBJECTIVE: To evaluate the effect of intravesical hyaluronic acid (HA) treatment on inflammatory cells and the severity of inflammation in an interstitial cystitis rat model created with hydrogen chloride (HCL) via immunohistochemical studies and myeloperoxidase activity for the first time in the literature. MATERIALS AND METHODS: A total of 30 adult female white Rattus Norvegicus rats were divided into 3 groups as the HCL group, hyaluronic acid treatment (HCL-HA) group and control group. Chemical cystitis was created by administering HCL(400 microL,10 mM) except control group. A single dose of intravesical HA(0.5 mL,0.8 mg/mL) was administered to the treatment group. The bladder tissues of all subjects were immunohistochemically stained. The cell surface markers were used to evaluate inflammatory cell infiltration. Mast cell activation and IL-6 was evaluated to assess the inflammation and severity of inflammation, respectively. Myeloperoxidase activity was measured as it shows neutrophil density. Statistical significance was accepted as P<0.05. RESULTS: It was observed that there was rich monocyte, T lymphocyte, B lymphocyte, and Natural Killer cells infiltration and high IL-6 levels in the bladder tissue after the intravesical hydrogen chloride instillation, especially in the stroma layer(p<0.005). In the HCL-HA group, severity of inflammation had statistically significantly regressed to the levels of the control group(p<0.005). An increase was observed in the bladder myeloperoxidase activity of the HCL group compared to the other two groups(p<0.05). CONCLUSIONS: Single dose intravesical hyluronic acid instillation reduces inflammatory cell infiltration and the severity of bladder inflammation in the rat model of bladder pain syndrome/interstitial cystitis.


Asunto(s)
Cistitis Intersticial/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Vejiga Urinaria/efectos de los fármacos , Administración Intravesical , Animales , Cistitis Intersticial/inducido químicamente , Cistitis Intersticial/patología , Modelos Animales de Enfermedad , Femenino , Ácido Clorhídrico , Ratas , Índice de Severidad de la Enfermedad , Vejiga Urinaria/patología
5.
J Reprod Immunol ; 161: 104173, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38043434

RESUMEN

The balance of the inflammatory response is indispensable during pregnancy. Inflammasomes are the cytosolic supramolecular protein complexes activated by pattern recognition receptors. These receptors recognize the pathogen and damage/danger-associated molecular patterns. NLRP3 inflammasome complex consists mainly of NLRP3 (leucine-rich repeat-containing and pyrin domain-containing protein 3), a cytosolic sensor molecule, ASC (apoptosis-associated speck-like protein containing a CARD) protein and a cysteine protease pro-caspase-1 as an effector molecule. This complex has a role in producing inflammatory cytokines, interleukin 1 beta and interleukin 18, and inflammasome-dependent programmed cell death pathway pyroptosis. In this review, we focused on and summarised the NLRP3 inflammasome and its roles in normal and pathological pregnancies. The NLRP3 inflammasome pathway influences endometrial receptivity and embryo invasion by inducing epithelial-mesenchymal transition. Abnormal inflammasome activation in the endometrium may adversely affect endometrial receptivity. In addition, NLRP3 inflammasome pathway overactivation may mediate the abnormal inflammatory response at the maternal-fetal interface and be associated with pregnancy complications, such as recurrent implantation failure, pregnancy loss, pre-term birth and pre-eclampsia. Therefore, targeting the NLRP3 inflammasome pathway could develop a new therapeutic approach to prevent the aforementioned pregnancy pathologies.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Embarazo , Femenino , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Apoptosis , Citocinas/metabolismo , Piroptosis , Caspasa 1 , Interleucina-1beta/metabolismo
6.
Proc Natl Acad Sci U S A ; 107(35): 15577-82, 2010 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-20713718

RESUMEN

Immunophilin FK506-binding protein 52 (FKBP52) is a cochaperone that binds to the progesterone receptor (PR) to optimize progesterone (P(4))-PR signaling. We recently showed that Fkbp52-deficient (Fkbp52(-/-)) mice have reduced uterine PR responsiveness and implantation failure which is rescued by excess P(4) supplementation in a genetic background-dependent manner. This finding led us to hypothesize that FKBP52 has functions in addition to optimizing PR activity. Using proteomics analysis, we found that uterine levels of peroxiredoxin-6 (PRDX6), a unique antioxidant, are significantly lower in Fkbp52(-/-) mice than in WT and PR-null (Pgr(-/-)) mice. We also found that Fkbp52(-/-) mice with reduced uterine PRDX6 levels are susceptible to paraquat-induced oxidative stress (OS), leading to implantation failure even with P(4) supplementation. The same dose of paraquat did not interfere with implantation in WT mice. Moreover, treatment with antioxidants alpha-tocopherol and N-acetylcysteine (NAC) attenuated paraquat-induced implantation failure in P(4)-treated Fkbp52(-/-) mice. Functional analyses using mouse embryonic fibroblasts show that Fkbp52 deficiency associated with reduced PRDX6 levels promotes H(2)O(2)-induced cell death, which is reversed by the addition of NAC or by forced expression of PRDX6, suggesting that Fkbp52 deficiency diminishes the threshold against OS by reducing PRDX6 levels. These findings provide evidence that heightened uterine OS in Fkbp52(-/-) females with reduced PRDX6 levels induces implantation failure even in the presence of excess P(4). This study shows that FKBP52-PRDX6 signaling protects pregnancy from overt OS.


Asunto(s)
Estrés Oxidativo , Peroxiredoxina VI/metabolismo , Transducción de Señal/fisiología , Proteínas de Unión a Tacrolimus/metabolismo , Útero/metabolismo , Animales , Northern Blotting , Western Blotting , Implantación del Embrión/efectos de los fármacos , Endometrio/citología , Endometrio/metabolismo , Femenino , Perfilación de la Expresión Génica , Herbicidas/farmacología , Humanos , Hibridación in Situ , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ovariectomía , Paraquat/farmacología , Peroxiredoxina VI/genética , Embarazo , Progesterona/farmacología , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Proteínas de Unión a Tacrolimus/genética , Factores de Tiempo , Útero/efectos de los fármacos
7.
Int J Dev Biol ; 67(3): 91-100, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37937415

RESUMEN

Although preterm birth is among the preventable causes of maternal and infant death, its mechanism has not yet been clarified. When evaluated in terms of the results, the psycho-social burden of mother-infant losses and the costs of rehabilitation, care, and treatment for postpartum sequelae are high. When evaluated in terms of its causes, infection/inflammation has an important place. Therefore, it is essential to understand the role of pro- and anti-inflammatory proteins in the process. In our study, apelin and apelin receptor (APJ) expression in the cervix-uterus and placental axis were evaluated at tissue and protein levels in pregnant and non-pregnant control, sham, PBS, and LPS groups in the infection model in which LPS induction was performed by midline laparotomy, in CD-1 mice. The evaluation of this axis regarding apelin and apelin receptor in the preterm birth model is new in the literature. Apelin is expressed more intensely in uterine epithelial cells than in the cervix. In the placenta, expression is more intense in the junctional zone compared to other zones. Apelin protein levels decrease significantly in the cervix and placenta whereas it increases in the uterus. While no change was observed in the expression of the apelin receptor at the tissue and protein level in the cervix and uterus, it increased in both aspects in the placenta in the invasive procedure groups. We propose that the decrease in apelin protein due to LPS in the preterm delivery model may be related to the effort to compensate for the balance deteriorated in the pro-inflammatory direction with post-transitional modification at the tissue level. The tendency of apelin to increase with pregnancy has led to the conclusion that it is necessary for a healthy pregnancy. Although the apelin receptor does not change with inflammation, it is necessary to investigate the mechanisms associated with its stress and trauma-induced increase, since it increases in the invasive procedure group.


Asunto(s)
Trabajo de Parto Prematuro , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Ratones , Animales , Placenta/metabolismo , Receptores de Apelina/metabolismo , Apelina/metabolismo , Cuello del Útero/metabolismo , Lipopolisacáridos/metabolismo , Nacimiento Prematuro/metabolismo , Útero/metabolismo , Trabajo de Parto Prematuro/metabolismo , Inflamación
8.
Ann Anat ; 246: 152027, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36379349

RESUMEN

BACKGROUND: Fertilization, pre-implantation embryo development, implantation, and decidualization are critical for a healthy pregnancy. Successful implantation requires a competent blastocyst and a receptive uterus. Apelin was purified from the bovine stomach in 1998. Apelin receptor (APJ) is a member of G protein-coupled receptors. Apelin/APJ system's physiological role was shown in cardiovascular system, immune response, stress response, fluid regulation, nutrient uptake, angiogenesis, and adipoinsular axis; however, whether apelin/APJ system plays a role in implantation is unknown. In our study, we aimed to evaluate the localization and expressions of the apelin/APJ system in the peri-implantation period mouse uterus. METHODS: Uteri and implantation sites were collected from mice on the estrous phase and the 1st, 4th, 5th, 6th, and 8th days of pregnancy. Also, inter-implantation sites were collected from the 5th day of the pregnancy group. Localization and expressions of apelin and APJ were determined by immunohistochemistry and Western blot, respectively. RESULTS: Apelin and APJ were expressed in the luminal and gland epithelium, the stroma of all experimental groups. Two isoforms of apelin-8 and 16 kDa were detected by Western blot. While apelin expression increased from the estrous to the 8th day of pregnancy, APJ expression increased from the estrous to the 4th day of pregnancy, reached the highest expression level, then decreased. CONCLUSIONS: Our findings suggest that the apelin/APJ system might be involved in implantation and decidualization. Our findings will guide further studies and may help elucidate the underlying causes of implantation failure and pregnancy loss.


Asunto(s)
Receptores de Apelina , Apelina , Implantación del Embrión , Animales , Bovinos , Femenino , Ratones , Embarazo , Apelina/genética , Receptores de Apelina/genética , Endometrio/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Receptores Acoplados a Proteínas G/metabolismo , Regulación del Desarrollo de la Expresión Génica
9.
J Mol Histol ; 54(4): 297-312, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37344690

RESUMEN

Although pregnancy is initiated and maintained through highly complex mechanisms, it is essential to understand the events that occur before and during early pregnancy to understand a healthy implantation process. The Notch signal, thought to be involved in this process, is frequently the subject of research with its different aspects. To better understand the role of Notch signaling in the peri-implantation period of the mouse uterus, we investigated the state of expression and localization of Notch 3, Notch 4, Rbp-J, Hes1, Hes7, Hey2, HeyL, and Fbw7 in the uterus and implantation sites in early pregnancy. Balb/C mice were divided into groups D1, D4, D5, D6, and D8. For D5 and D6 groups, implantation sites were identified by intravenous injection of Chicago blue. IHC, WB, and QRT-PCR methods were used. Notch 3 was very strong positive on the 4th day of pregnancy. Notch 4 was highly expressed on days 4, 5, 6, and 8 of pregnancy when P4 levels were high. Hes 1 level was at the lowest on the 4th day of pregnancy. Hes 7 protein expression gradually increased from D1 to D8 in the uteri and implantation sites. Hey 2 expression was at the highest level on the 1st and 4th days. Hey L expression was on the apical of the glands. Fbxw7 that expression was high on the 1st and 4th days of pregnancy. Notch signaling may play an essential role in regulating endometrial receptivity. In addition, our Hes7 results are new to the literature.


Asunto(s)
Implantación del Embrión , Factores de Transcripción , Embarazo , Femenino , Ratones , Animales , Factores de Transcripción/metabolismo , Útero , Endometrio/metabolismo , Transducción de Señal , Receptores Notch/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética
10.
Biotech Histochem ; 98(2): 132-139, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36245360

RESUMEN

Nuclear factor-erythroid 2-related factor- 2 (Nrf2) is a nuclear transcription factor that facilitates transcription of genes for detoxification enzymes and antioxidant proteins. We investigated the distribution and expression of Nrf2 during the peri-implantation period. We detected Nrf2 in uteri of mice during estrus (control) and on days 1, 4, 5, 6 and 8 of pregnancy using immunohistochemistry, quantitative real-time polymerase chain reaction and western blotting. Nrf2 immunostaining was significantly greater on days 1, 5 and 6 of pregnancy compared to controls, and on days 4 and 8 of pregnancy; western blotting results were consistent with immunohistochemical observations. Nrf2 mRNA levels on days 5 and 8 were significantly higher than for control uteri. Increased expression of Nrf2 on days 1, 5 and 6 of pregnancy may be important for uterine receptivity, implantation and decidualization by protecting the developing embryo and uterus from the adverse effects of oxidative stress.


Asunto(s)
Implantación del Embrión , Factor 2 Relacionado con NF-E2 , Embarazo , Femenino , Ratones , Animales , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Útero/metabolismo , ARN Mensajero/metabolismo , Regulación de la Expresión Génica
11.
Turk J Gastroenterol ; 33(10): 822-830, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35946877

RESUMEN

BACKGROUND: Probiotics such as Lactobacillus and Bifidobacterium are among the supportive treatment methods to achieve effective results in ulcerative colitis. This study was established to investigate the effect of probiotics in experimental ulcerative colitis and to detect changes in mast cell and neuronal structures in this treatment method. METHODS: A total of 48 adult male rats were used to study the effects of probiotics on ulcerative colitis. The animals were divided into 6 groups as control, experimental colitis, and four probiotic protective groups. Three different bacterial strains were administered to the protective groups individually and in combination by gavage. PGP 9.5 antibody and mast cell tryptase were used for the detection of neuronal structures and mast cells. The number of Schwann cells and ganglia, size measurements of ganglia, and density of mast cells were evaluated. RESULTS: Compared to the control, an increase in the number of mast cells was detected in all groups. Especially the increase in the num- ber of mast cells was found to be statistically significant in combined probiotic administration. In the detection of neuronal structures, a significant increase in the number of Schwann cells and ganglia was detected in groups where probiotics were administered combined and individually. CONCLUSION: These results suggest that probiotics may play a role in the supporting effect of increasing the number of mast cells and neuronal structures, protecting the intestinal wall. We think that more specific and detailed studies should be conducted to evaluate the protective/therapeutic effect of probiotics in future studies.


Asunto(s)
Colitis Ulcerosa , Colitis , Probióticos , Animales , Recuento de Células , Colitis Ulcerosa/tratamiento farmacológico , Hipertrofia , Masculino , Mastocitos , Probióticos/farmacología , Probióticos/uso terapéutico , Ratas , Triptasas/uso terapéutico
12.
Rom J Morphol Embryol ; 62(1): 179-190, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34609420

RESUMEN

Testicular torsion is a urological problem that causes subfertility and testicular damage in males. Testis torsion and detorsion lead to ischemia-reperfusion (IR) injury in the testis. Testicular IR injury causes the increase of reactive oxygen species (ROS), oxidative stress (OS) and germ cell-specific apoptosis. In this study, we aimed to investigate whether Carvacrol has a protective effect on testicular IR injury and its effects on Kir6.2 channels, which is a member of adenosine triphosphate (ATP)-dependent potassium channels. In the study, 2-4 months old 36 albino Wistar rats were used. For experimental testicular IR model, the left testis was rotated counterclockwise at 720° for two hours, and after two hours following torsion, detorsion was performed. Carvacrol was dissolved in 5% Dimethyl Sulfoxide (DMSO) at a dose of 73 mg∕kg and half an hour before detorsion, 0.2 mL was administered intraperitoneally. In testicular tissues, caspase 3 and Kir6.2 immunoexpressions were examined. Serum malondialdehyde (MDA) and testosterone levels were measured. Apoptotic cells and serum MDA levels were significantly decreased and Kir6.2 activation was significantly increased in Carvacrol-administrated IR group. As a result of our study, Carvacrol may activates Kir6.2 channels and inhibits apoptosis and may have a protective effect on testicular IR injury.


Asunto(s)
Daño por Reperfusión , Torsión del Cordón Espermático , Adenosina Trifosfato , Animales , Apoptosis , Cimenos , Humanos , Masculino , Malondialdehído , Potasio , Canales de Potasio , Ratas , Daño por Reperfusión/tratamiento farmacológico , Torsión del Cordón Espermático/tratamiento farmacológico , Testículo
13.
Tissue Cell ; 56: 41-51, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30736903

RESUMEN

Parkinson's disease (PD) is a degenerative disorder of the human central and peripheral nervous systems. n-3 fatty acids docosahexaenoic acid (DHA, C22: 6n-3) and eicosapentaenoic acid (EPA) as well as apelin have anti-inflammatory effects in various cells. At the same time, apelin has anti-oxidative and anti-apoptotic effects. The study was conducted to determine the effect of DHA on the distribution of apelin and apelin receptor (APJ) in the central nervous system in 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-induced PD model. DHA treatment decreased the return time and total down time in the Parkinson group which were measured by pole test. Besides, the ambulatory activity, distance and total locomotor activity were increased by DHA in the PD model of animals. The time mice remained on the rotating rod mile was also significantly increased by DHA treatment in MPTP injected animals. The apelin expression in the pons of mice in the Parkinson, DHA and Parkinson + DHA groups were lower compared to the Control group. When apelin and apelin receptor expressions in cerebrum were examined, there was no statistically significant difference between the groups. When apelin receptor expression in cerebellum was examined, the difference between the Control and Parkinson + DHA, Parkinson and Parkinson + DHA, DHA and Parkinson + DHA groups were statistically significant. Apelin receptor expressions in pons of the Parkinson, DHA and Parkinson + DHA groups were lower compared to the Control group. Apelin protein levels of cerebellum and pons were found to be decreased in DHA group compare with Control group. In conclusion; DHA has been implicated in the expression of the apelin receptor and has reduced the expression of APJ receptor.


Asunto(s)
Receptores de Apelina/genética , Apelina/genética , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Regulación de la Expresión Génica , Humanos , Ratones , Sistema Nervioso/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/patología
14.
J Reprod Immunol ; 78(2): 158-65, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18423887

RESUMEN

Trophoblast expression of the non-classical MHC, HLA-G, is considered essential for feto-maternal immune tolerance and successful placentation in pregnancy. The HLA-G 14bp polymorphism in the 3'-untranslated region (UTR) of the HLA-G gene has been reported to be associated with development of pre-eclampsia (PE). In this study, maternal (peripheral blood, n=54) and fetal (cord blood, n=57) HLA-G 14bp genotypes have been determined by PCR in pre-eclamptic and normal pregnancies. In addition, HLA-G 14bp gene expression in decidua basalis (n=59) was analyzed by RT-PCR. The pre-eclamptic syndrome was neither associated with the HLA-G 14bp genotype (maternal or fetal), nor with altered decidual HLA-G 14bp gene expression. Furthermore, the HLA-G 14bp mRNA expressed in decidua basalis was of fetal origin and all potential transcripts, as predicted from the fetal HLA-G 14bp genotype, were expressed. In contrast to previous findings, we found no correlation between the HLA-G 14bp polymorphism and fetal growth. In conclusion, the fetal HLA-G 14bp genotype is reflected in the decidual HLA-G mRNA splice form profile, but does not appear to be associated with increased risk for development of PE.


Asunto(s)
Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Preeclampsia/genética , Adulto , Alelos , Decidua/metabolismo , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA/sangre , Antígenos HLA/metabolismo , Antígenos HLA-G , Antígenos de Histocompatibilidad Clase I/sangre , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Preeclampsia/metabolismo , Embarazo
15.
Acta Histochem ; 110(5): 408-17, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18377963

RESUMEN

We aimed to investigate the distribution pattern of proliferating cell nuclear antigen (PCNA) by immunohistochemistry and Western blot in placentas of control and diabetic rats at different stages of pregnancy. It is still not clear how proliferation is coordinated and how this coordination is affected by diabetes in the placenta. Diabetes was induced by streptozocin on the first day of pregnancy. Animals were sacrificed on days 11, 13, 17 and 21 of pregnancy. In control placentas immunolabeling intensity of PCNA was the highest on days 11 and 13 of pregnancy and decreased with progression of pregnancy. In the diabetic groups immunolabeling was less intense on days 11 and 13 of pregnancy compared to controls. However, in parallel with placental weights, PCNA immunopositivity was more intense in diabetic groups than control groups on days 17 and 21 of pregnancy, and the difference was statistically significant on day 17. According to Western blot data, on days 11 and 13 of pregnancy the amount of PCNA was greater in control groups than in the diabetics, whereas it was greater in diabetic groups than the controls on days 17 and 21 of pregnancy. We conclude that PCNA may play a role in abnormal placenta formation resulting from diabetes.


Asunto(s)
Placenta/metabolismo , Placentación , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Animales , Ciclo Celular , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Femenino , Inmunohistoquímica/métodos , Masculino , Placenta/patología , Embarazo , Preñez , Antígeno Nuclear de Célula en Proliferación/fisiología , Ratas , Ratas Wistar , Estreptozocina/farmacología
16.
Acta Histochem ; 110(5): 397-407, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18272209

RESUMEN

The presence of progenitor/stem cells in human articular cartilage remains controversial. Therefore, we attempted to isolate and culture progenitor/stem cells and to investigate their phenotypic characteristics. Biopsies were obtained (with consent) from patients undergoing arthroscopic surgery. Full depth explants were fixed and cryosectioned or enzymatically digested and the resulting cells cultured and plated on fibronectin-coated dishes. Chondrocytes were cultured until colonies of >32 cells were present. Colonies were trypsinized and expanded in monolayer for pellet culture. Immunolocalization of Notch and its ligands were detected in vivo and in vitro using immunocytochemistry. In vitro studies investigated differences in immunolocalization of Notch and its associated ligands in colony-forming cells and small clusters of non-colony-forming cells. The ultrastructure of the chondroprogenitors was examined by scanning and transmission electron microscopy. Results revealed that the immunolocalization of Notch-1 and its ligand Delta were concentrated in regions closest to the articular surface. Notch-1 was also densely localized in the deeper zone of articular cartilage. Notch-2 immunolabeling was densely localized in all zones of articular cartilage. Jagged-1 was concentrated in the deeper regions of articular cartilage. Notch-1, Delta and Jagged-1 were more abundant in colony-forming cells than non-colony-forming chondrocytes in vitro. Notch-3, Notch-4 and Jagged-2 were absent from all regions of the articular cartilage tissues and cultured cartilage cells in vitro. Ultrastructurally, chondrocytes cultured in monolayer dedifferentiated to fibroblast-like cells with cell surface processes of varying lengths, pellet cultured cells varied in morphology, as flattened and rounded. In conclusion, we propose that adult human articular cartilage may contain cells having progenitor cell features.


Asunto(s)
Cartílago Articular/metabolismo , Condrocitos/citología , Inmunohistoquímica/métodos , Proteínas de la Membrana/metabolismo , Receptores Notch/metabolismo , Células Madre/citología , Adulto , Biopsia , Cartílago/metabolismo , Fibroblastos/citología , Fibronectinas/química , Humanos , Péptidos y Proteínas de Señalización Intracelular , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Modelos Biológicos
17.
Acta Histochem ; 120(3): 196-204, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29395316

RESUMEN

Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work. In our experimental study, a total of 35 (hypertensive group: 20, control group: 15) Rattus Norvegicus Wistar albino rats were used. In order to obtain our hypertension model, our experimental animals were given L-NAME together with drinking water for six weeks. After six weeks, the experimental procedures were terminated. Heart and kidney tissues of the hypertensive and control group were obtained. Expression of apelin and apelin receptor (APJ) was demonstrated by immunohistochemical and Western Blot protocols. Hypertrophic cardiac atrium of the hearts of the large cavities, interventricular septum and myocardium to the disintegration, as well as an increase in the diameter of the coronary artery has been observed. In general, kidney tissues of the hypertensive group showed narrowing in cortical renal structures and enlargement in structures in the renal medulla. As a result, in hypertensive cases, there was an increase in expression of Apelin and APJ receptor in heart tissue, and a decrease in expression of Apelin and APJ receptor in kidney tissue. We think that our findings may contribute to experimental or clinical studies related to hypertension and apelin.


Asunto(s)
Receptores de Apelina/metabolismo , Apelina/metabolismo , Hipertensión , Riñón/metabolismo , Miocardio/metabolismo , Animales , Western Blotting , Peso Corporal , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Hipertensión/inducido químicamente , Inmunohistoquímica , NG-Nitroarginina Metil Éster/toxicidad , Ratas , Ratas Wistar , Estándares de Referencia
18.
Tissue Cell ; 51: 91-96, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29162289

RESUMEN

BACKGROUND: The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. AIM: The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. METHODS: The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. RESULTS: F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. CONCLUSION: Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions.


Asunto(s)
Receptores de Apelina/metabolismo , Apelina/metabolismo , Factor Natriurético Atrial/biosíntesis , Miocardio/metabolismo , Estrés Psicológico/metabolismo , Animales , Homeostasis/fisiología , Ratas , Ratas Wistar
19.
J Physiol Sci ; 67(3): 373-385, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27369695

RESUMEN

The objective of this study was to explore the role of apelin in the healing of gastric lesions induced by stress. Male Wistar rats were exposed to water immersion and restraint stress (WIRS) for 6 h with or without the apelin receptor antagonist F13A. The rats were killed on the 1st, 3rd, 5th or 10th day after the end of stress induction. Apelin and hypoxia-inducible factor-1α expression was increased on the 1st day after the end of stress exposure and was decreased daily thereafter. However, F13A retarded the healing of gastric lesions by preventing the improvement of mucosal blood flow, prostaglandin E2 production and vascular endothelial growth factor expression in rats exposed to WIRS. Additionally, F13A increased the gastric 4-hydroxynonenol + malondialdehyde content on the 1st and 3rd days after the end of stress induction but did not affect the change in gastric mucosal nitric oxide levels. In conclusion, apelin may be a regulatory protein involved in the healing mechanism of stress-induced gastric damage.


Asunto(s)
Deshidratación/metabolismo , Mucosa Gástrica/metabolismo , Inmersión/fisiopatología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Restricción Física/fisiología , Estrés Fisiológico/fisiología , Animales , Apelina , Deshidratación/fisiopatología , Mucosa Gástrica/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Estómago/fisiopatología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Agua/metabolismo
20.
Pathol Oncol Res ; 22(1): 87-94, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26341090

RESUMEN

Prostate Cancer (PCa) holds the second place in terms of cancer-related mortality rate among men. The Notch signalling pathway regulates the proliferation and differentiation in embryonic and adult tissues and determines the cell fate. The body of knowledge in the present literature is currently controversial about the effect of the Notch pathway on prostatic cancer. Therefore, the present study aimed to examine the immunolocalization and expression levels of Notch1-4, Jagged1-2, Delta, HES1 and HES5 from among the members of the Notch signalling pathway in tissues of normal, prostatic intraepithelial neoplasia (PIN) and malignant prostate. The current study included a sample of 20 patients with localised prostatic adenocarcinoma, 18 patients with high grade PIN (H-PIN) and 18 normal prostatic tissue. Immunolocalisations of Notch1, 2, 3, 4, Jagged1, 2, Delta, HES1 and HES5 were identified through the immunohistochemical method. The findings of the present study showed that all in-scope members of the Notch signalling pathway were localised in PIN structures to a greater extent than in other tissues and from amongst these members, specifically Notch1, Notch4, Jagged1 and HES1 were at more significant levels. Consequently, the findings of the present study may indicate that the Notch signalling pathway can play a role especially in the formation of PIN structures.


Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Próstata/metabolismo , Neoplasia Intraepitelial Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Receptores Notch/metabolismo , Transducción de Señal/fisiología , Adenocarcinoma/patología , Adulto , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Unión al Calcio/metabolismo , Estudios de Casos y Controles , Estudios de Seguimiento , Proteínas de Homeodominio/metabolismo , Humanos , Técnicas para Inmunoenzimas , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína Jagged-1 , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología , Proteínas Serrate-Jagged , Factor de Transcripción HES-1
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