• 대한수의학회지
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• 제43권4호
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• pp.551-554
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• 2003

Nitric oxide synthase (NOS) has been reported in uterus. We examined the expression of the NOS isoforms, constitutive endothelial (eNOS) and inducible NOS (iNOS), in bovine uterus by immunohistochemistry. eNOS immunoreactivity was localized predominantly to the endothelial cells that line uterine microvessels and to endometrial glandular epithelial cells, but was barely detectable in endometrial stromal cells. iNOS immunostaining was detected in glandular epithelial and stromal cells in the endometrium and in the endothelial cells of myometrial blood vessels. These findings suggest that both eNOS and iNOS may play important roles in the physiology of the uterus, possibly by generating NO.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.263-275
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• 2019

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

• 대한수의학회지
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• 제31권1호
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• pp.1-10
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• 1991

The present investigation was focussed on histochemical and electron microscopical observations of utero-vaginal(U-V) glands in U-V junctions of domestic hens. In histochemical observations, fine granules by PAS technique for mucopolysaccharides and nile blue stain for acidic lipids were slightly stained on the cytoplasm of U-V glandular epithelium. Larger granules by Sudan black B stain for neutral fat and phospholipids and Sudan III stain for neutral fat were heavily stained on the perinuclear region of the U-V gland epithelial cells. These positive materials were heavily stained on the U-V glandular epithelium of lowfecundity hens and non-laying hens. In scanning electron microscopic findings of the U-V junction surface, the orifices of U-V glands are seen as the crater-like invagination. The neck of the U-V gland and the epithelium of U-V iunction were covered by ciliated epithelial cells. Aggregates of spermatozoa are observed often to be on the necks of the U-V gland. These spermatozoa heads are embedded in the glandular tubules and many spermatozoa tails are free on the epithelium of uterine surface. In transmission electron microscopic findings, the epithelial cells of the U-V glandular orifices were ciliated, columnar cells. The apical regions of these cells contained numerous electrondense, round secretory granules of uniformly size. The epithelial cells of the U-V glandular tubule were columnar or pyramid shape with round or oval nuclei. These epithelial cells have numerous microvilli and also contained electron-dense, round secretary granules of uniformly size and electron-lucent vesicles of various size. Spermatozoa are seen as the cross-sections of various regions of heads and tails in glandular tubules. Also spermatozoa arranged longitudinally parallel within the glandular tubules.

• Animal Bioscience
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• 제34권6호
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• pp.993-1005
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• 2021

Objective: Zearalenone (ZEA) has estrogen-like effects. Our previous study has shown that ZEA (0.5 to 1.5 mg/kg) could induce abnormal uterine proliferation through transforming growth factor signaling pathway. To further study the other regulatory networks of uterine hypertrophy caused by ZEA, the potential mechanism of ZEA on porcine endometrial epithelial cells (PECs) was explored by the Illumina Hiseq 2000 sequencing system. Methods: The PECs were treated with ZEA at 0 (ZEA0), 5 (ZEA5), 20 (ZEA20), and 80 (ZEA80) µmol/L for 24 h. The collected cells were subjected to cell cycle, RNA-seq, real-time quantitative polymerase chain reaction, immunofluorescence, and western blot analysis. Results: The proportion of cells in the S and G2 phases decreased (p<0.05), but the proportion of cells in the G1 phase increased (p<0.05) in the ZEA80 treatment. Data analysis revealed that the expression of Wnt pathway-related genes, estrogen-related genes, and mitogen-activated protein kinase pathway-related genes increased (p<0.05), but the expression of genetic stability genes decreased (p<0.05) with increasing ZEA concentrations. The relative mRNA and protein expression of WNT1, β-catenin, glycogen synthase kinase 3β (GSK-3β) were increased (p<0.05) with ZEA increasing, while the relative mRNA and protein expression of cyclin D1 (CCND1) was decreased (p<0.05). Moreover, our immunofluorescence results indicate that β-catenin accumulated around the nucleus from the cell membrane and cytoplasm with increasing ZEA concentrations. Conclusion: In summary, ZEA can activate the Wnt/β-catenin signaling pathway by up-regulating WNT1 and β-catenin expression, to promote the proliferation and development of PECs. At the same time, the up-regulation of GSK-3β and down-regulation of CCND1, as well as the mRNA expression of other pathway related genes indicated that other potential effects of ZEA on the uterine development need further study.

• Asian-Australasian Journal of Animal Sciences
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• 제30권5호
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• pp.643-652
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• 2017

Objective: Prostaglandins (PGs) function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ATP-binding cassette, subfamily C, member 4 (ABCC4) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1) are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta. Methods: Uterine endometrial tissues were obtained from gilts on day (D) 12 and D15 of the estrous cycle and days 12, 15, 30, 60, 90, and 114 of pregnancy. Results: ABCC1, ABCC9, SLCO4C1, and SLCO5A1 mRNAs were expressed in the uterine endometrium, and levels of expression changed during the estrous cycle and pregnancy. Expression of ABCC1 and ABCC9 mRNAs was localized mainly to luminal and glandular epithelial cells in the uterine endometrium, and chorionic epithelial cells during pregnancy. Conceptuses during early pregnancy and chorioallantoic tissues from mid to late pregnancy also expressed these PG transporters. $Estradiol-17{\beta}$ increased the expression of ABCC1 and SLCO5A1, but not ABCC9 and SLCO4C1 mRNAs and increasing doses of $interleukin-1{\beta}$ induced the expression of ABCC9, SLCO4C1, and SLCO5A1 mRNAs in endometrial explant tissues. Conclusion: These data showed that several PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 were expressed at the maternal-conceptus interface, suggesting that these PG transporters may play an important role in the establishment and maintenance of pregnancy by regulating PG transport in the uterine endometrium and placenta in pigs.

• BMB Reports
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• 제55권8호
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• pp.370-379
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• 2022

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권5호
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• pp.253-260
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• 2019

Background: Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). Methods: WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B ($NF-{\kappa}B$) and p38 and the expression of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$, cyclooxygenase (COX)2, and prostaglandin E $(PGE)_2$ were quantified using western blotting and RT-PCR, respectively. Results: Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of $NF-{\kappa}B$, and expression of COX2 and $PGE_2$ in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of $IL-1{\beta}$ and $TNF-{\alpha}$ expression was also observed with RT-PCR. Conclusion: Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.

• 대한한방부인과학회지
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• 제19권2호
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• pp.141-161
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• 2006

Purpose : This study was performed to investigate the effects of Sobokchukeo- Tang(SCT) on the experimentally-induced endometriosis in rats. Materials and Methods : Endometriosis was induced via the surgical autotransplantation technique in rats. A laparotomy was performed and a $4\;{\times}\;4\;mm$ of the right uterine horn was resected incised and sutured to the peritoneum. And the animals divided into control(n=8) and SCT-treated group(n=8). SCT(1,000 mg/head) was administered orally for 15 days after operation. The weights(body, left uterus, and ovaries) and concentrations of cytokines(MCP-1,$TNF-{\alpha}$, $IL-l{\beta}$) were measured. Histopathology, immunohistochemistry for COX-2, and histochemistry for mast cells of the transplanted uterine tissues were performed. Results : - The $volume(mm^3)$ of transplanted uterine tissues of SCT-treated group$(92.88{\pm}41.89)$ was significantly(p<<0.01) decreased than the control group $(404.50{\pm}317.68)$. The concentration(pg/ml) of MCP-1 in ascites of SCT-treated group$(5,256{\pm}1,209)$ was significantly(p<<0.001) decreased than the control group$(8,632{\pm}1,245)$. - The concentration(pg/ml) of $TNF-{\alpha}$ in ascites of SCT-treated group$(521.8{\pm}306.1)$ was significantly(p<<0.01) decreased than the control group$(1,245.2{\pm}362.2)$. - The percentage of COX-2 positive epithelial layer in transplanted uterine tissues of SCT-treated group$(25.0{\pm}7.3)$ was significantly(p<<0.001) decreased than the control group$(50.2{\pm}8.2)$. - The number of mast cells in the stroma of transplanted uterine tissues of SCT-treated group$(16.5{\pm}6.8)$ was significantly(p<<0.05) decreased than the control group$(26.0{\pm}7.7)$. - The number of mast cells in the periphery of transplanted uterine tissues of control group$(71.3{\pm}18.5)$ was significantly(p<<0.01) decreased than the control group$(109.3{\pm}30.2)$. - Proliferation of epithelia, infiltration of inflammatory cells, and microanglogenesis in transplanted uterine tissues of treated group were weakly observed than the control group. Conclusion : From the above results, Sobokchukeo-Tang(SCT) has an inhibitory effect on the development of transplanted uterine tissue in rats and it is related to the decreased concentration of MCP-1 and $TNF-{\alpha}$, and decreased expression of COX-2, and decreased infiltration of mast cells by administration of Sobokchukeo-Tang.

• 한국식품위생안전성학회지
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• 제21권4호
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• pp.258-262
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• 2006

환경호르몬 물질의 생체내에서의 상호작용에 의한 상자 또는 상승 작용을 알아보기 위하여 환경호르몬 물질들을 조합하여 마우스에 처치한 후 생체내에서 생식기의 변화 정도를 조직병리학적으로 관찰하였다. 암컷 ICR마우스에 난소적출술을 실시하고 2주 후에 DEHP, DBP, BPA의 환경호르몬 물질을 단독 또는 두개씩 조합하여 마우스에 피하로 주입하였다. 육안적인 변화에서는 모든 군에서 이상이 관찰 되지 않았으며, 부검 후 자궁의 무게를 측정한 결과에 있어서도 유의적인 변화를 관찰할 수 없었으나, 자궁 내 fluid존재에 있어서는 E2 단독 투여 군과 E2와 함께 투여한 모든 그룹(E2+DEHP, E2+DBP, E2+BPA)에서 관찰되었다. 조직병리학적인 관찰에 있어서는.자궁상피세포, 질 상피세포, 유선의 변화 그리고 난관 직경의 변화를 관찰하였다. 그 결과 민감도에 있어서 가장 유의적인 변화를 보인 항목은 질 상피세포의 변화였으며, 환경호르몬 물질을 두개씩 혼합하여 처치한 그룹에 있어 단독으로 처치한 그룹과 비교 시 변화의 정도가 심한 것이 일부 관찰 되었으나 통계학적으로 유의성을 가지고 있다고 결론을 내리기 는 힘들었다. 결론적으로 환경호르몬물질간의 생체내에서 상가 혹은 상승작용에 대한 명확한 결과는 도출할 수 없었으나, 환경호르몬물질이 생체내 작용하는 데에 있어서 서로 간에 상승작용을 할 수 있다는 가능성은 충분한 것으로 판단되어진다.

• Clinical and Experimental Reproductive Medicine
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• 제48권2호
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• pp.132-141
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• 2021

Objective: Lipopolysaccharide (LPS) from Gram-negative bacteria causes poor uterine receptivity by inducing excessive inflammation at the maternal-fetal interface. This study aimed to investigate the detrimental effects of LPS on the attachment and outgrowth of various types of trophoblastic spheroids on endometrial epithelial cells (ECC-1 cells) in an in vitro model of implantation. Methods: Three types of spheroids with JAr, JEG-3, and JAr mixed JEG-3 (JmJ) cells were used to evaluate the effect of LPS on early implantation events. ECC-1 cells were treated with LPS to mimic endometrial infection, and the expression of inflammatory cytokines and adhesion molecules was analyzed by quantitative real-time polymerase chain reaction and western blotting. The attachment rates and outgrowth areas were evaluated in the various trophoblastic spheroids and ECC-1 cells treated with LPS. Results: LPS treatment significantly increased the mRNA expression of inflammatory cytokines (CXCL1, IL-8, and IL-33) and decreased the protein expression of adhesion molecules (ITGβ3 and ITGβ5) in ECC-1 cells. The attachment rates of JAr and JmJ spheroids on ECC-1 cells significantly decreased after treating the ECC-1 cells with 1 and 10 ㎍/mL LPS. In the outgrowth assay, JAr spheroids did not show any outgrowth areas. However, the outgrowth areas of JEG-3 spheroids were similar regardless of LPS treatment. LPS treatment of JmJ spheroids significantly decreased the outgrowth area after 72 hours of coincubation. Conclusion: An in vitro implantation model using novel JmJ spheroids was established, and the inhibitory effects of LPS on ECC-1 endometrial epithelial cells were confirmed in the early implantation process.