• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5445-5450
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• 2012

Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.4
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• pp.273-277
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• 2004

Intramural pregnancy is an unusual ectopic gestation located within the uterine wall, completely surrounded by myometrium and separate from the uterine cavity, fallopian tube, or round ligament. It is known to be difficult to diagnose, and associated with a high rate of uterine rupture. We report a case of intramural pregnancy in which early diagnosis was made and successful treatment was done by dilatation and curettage. Diagnostic laparoscopy confirmed the absence of uterine rupture during the procedure. Therefore, conservation of fertility can be possible with early diagnosis of intramural pregnancy. To our knowledge, this is the first case report of intramural pregnancy following IVF-ET in Korea.

• Korean Journal of Animal Reproduction
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• v.19 no.2
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• pp.119-127
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• 1995

These studies were carried out to examine the estradiol-17$\beta$ levelsin plasma and ovarian tissues, as well as the contents of collagen and catecholamines in the uterus, and to determine the effects of GnRH administrations of uterine involution in postpartum Korean native goats. Plasma concentrations of estradiol-17$\beta$ were 63.81$\pm$8.00 pg/ml at day 1 of kidding, declined to 36.78$\pm$22.90 ng/ml at day 24 and decreased progressively to 27.81$\pm$17.06 and 12.46$\pm$8.13 pg/ml at days 30 and 36 postpartum, respectively. In ovarian tissues, the concentrations of estaiol-17$\beta$ were increased just before parturition and decreased immediately after parturition. The plasma estradiol-17$\beta$ levels were slightly higher on days 12 and then decreased gradually after parturition. The concentraitons of estradiol-17$\beta$ in the ovaries of postpartum goats were increased at day 36 after treatments with GnRH. The total hydroxyproline contents in the uterus was slightly higher prior to parturition and decreased gradually with the postpartum intervals after parturition. Hydroxyproline concentraitons in the uterus were decreased at days 24 and 36 postpartum after treatments with GnRH. The norepinephrine concentrations in myometrium from the pregnant and postpartum goats were correspondingly low both immediately before and after partuition. Norepinephrine concentrations in the pregnant horn of the uterus were increased from days 12 to 36 of postpartum and those levels of the non-pregnant horn were also increased from days 24 to 36 postpartum. Slightly higher concentrations were present in the non-pregnant horn in comparison to the pregnant horn but these differences were not significant. Postpartum, the uterine norepinephrine concentration was slightly increased at day 36 after treatments with GnRH. Dopamine concentrations were greater than those of norepinephrine. The concentrations of dopamine in the uterus of pregnant goats was not significantly different from that in the postpartum animals. Dopamine concentraitons of pregnant horn in postpartum goats were increased at day 24 after treatments with GnRH.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.61-61
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• 2003

Aquaporins (AQPs)는 다양한 상피세포와 내피세포에 존재하며 다량의 물 수송을 촉진하는 막성단백질로 현재 11개의 AQP가 (AQP0-10) 발견되었으나, 아직 생리적, 기능적 분석은 불충분한 상태이다. 생쥐의 자궁내막은 발정주기 동안 호르몬의 자극에 따라 부풀어오르거나 수축하는 변화를 보이며 에스트로젠과 몇몇 혈관에 작용하는 매개체에 의해 자궁 혈관의 투수성이 증가한다는 보고는 있으나, 자궁액의 수송 메커니즘에 대해서는 뚜렷하게 밝혀진 바가 없다. 발정기의 생쥐 자궁은 자궁내막세포의 증식과 함께 수화되는 특징을 보이며 자궁내강으로 물이 수송되어 luminal fluid의 점성이 낮아지는 현상이 나타나는데, 이 때 AQP가 water channel로서 중요한 역할을 할 것으로 보고 본 실험에서는 면역조직화학법(immunohistochemistry)과 역전사중합효소연쇄반응(Reverse-transcriptase polymerase chain reaction)을 통해 발정기 자궁의 수화와 AQP 발현의 상관성에 대해 알아보고자 하였다. 면역조직화학법의 결과 발정주기의 다른 시기에 비해 발정기(estrus phase)에 자궁상피세포에 AQP4, 5, 8 protein이 다량 존재하는 것으로 밝혀졌고, 근육층(myometrium)에서의 발현은 발정주기 동안 차이가 없었다. Whole uterus로 RT-PCR을 수행한 결과 AQP4, 5, 8 mRNA는 luteal phase에 비해 follicular phase에 더 많이 발현하는 것으로 확인되었다. 또한 LCM(Laser Capture Microdissection) system을 이용하여 luminal epithelium과 stromal cell을 분리하여 RT-PCR을 수행한 결과 AQP4, 5, 8 mRNA는 stromal cell 보다는 luminal epithelium에 더 많이 발현하며, 이 역시 follicular phase에 발현량이 증가함을 확인하였다. 이러한 결과로 미루어 생쥐 자궁에서 AQP4, 5, 8은 발정주기 내막에 발현이 증가하며 이는 자궁내강 안으로 수분을 수송하는데 주요한 기작으로 사료되며 estrogen에 의한 조절 가능성을 암시한다.

• Korean Journal of Veterinary Research
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• v.22 no.1
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• pp.1-8
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• 1982

The effect of acetylcholine, oxytocin and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on cyclic nucleotide levels in estrogen-primed rabbit whole uterus were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiestrase inhibitor, and indomethacin, a prostagandin inhibitor. In the absence of MIX, acetylcholine increased guanosine 3', 5'-cyclic monophosphate (cGMP), but had no effect on adenosine 3', 5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin had no influence on cGMP, but decreased cAMP levels. $PGF_{2{\alpha}}$ increased cGMP and decreased cAMP levels. MIX increased both cAMP and cGMP levels. Oxytocin and $PGF_{2{\alpha}}$ further increased cGMP levels, indicating activation of guanylate cyclase activity. The ratio of cAMP/cGMP was decreased by uterine stinulants both in presence and absence of MIX. Indomethacin elevated cAMP and cGMP revels. The effects of uterine stimulants in the presence of indomethacin on cyclic nucleotide levels were varied from tissue to tisse. In general, oxytocin decreased cGMP and $PGF_{2{\alpha}}$ increased cAMP/cGMP levels, but the effects were statisically nonsignicficant. The cAMP/cGMP ratio was increased by uterine stimulant in the presence of indomethacin. In conclusion, uterine stimulants eased cAMP/cGMP ratio which indicates that the uterine stimulants have opposing effects on adenylate cyclase and guanylate cyclase activities. The endometrium plays a role in the regulation of cyclic nucleotide levels and uterine contraction by means of PG synthesis. Indomethacin has an unknown activities besides both of PG synthetase and phosphodiesterase inhibitions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7061-7064
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• 2014

Background: To assess the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of intraoperative gross examination (IGE) of uterine specimens in determining deep myometrial invasion and cervical invasion compared to final histology. Materials and Methods: The clinical, surgical and histological data of all FIGO stage I-II endometrial cancer (EC) patients who had primary surgery were reviewed. Results of the IGE for myometrial invasion and cervical invasion were compared to the final histology. The sensitivity, specificity, PPV, NPV, and accuracy of the IGE in determining deep myometrial invasion and cervical invasion were calculated. Association between clinico-pathological factors and discrepancy between IGE and final histology in the determination of myometrial invasion was also assessed. A p-value of <0.05 was considered significant. Results: From January 2007 to December 2012, 179 patients diagnosed with clinical stage I-II endometrial cancer underwent surgical staging. The sensitivity and specificity of IGE in detecting deep myometrial invasion were 42.4% and 90.0%, respectively, and the PPV and NPV were 67.6% and 76.1%. The overall accuracy of IGE was 74.3%. The sensitivity and specificity of IGE in identifying cervical invasion were 28.6% and 97.5%, respectively, while the PPV and NPV were 60.0% and 91.1%. The overall accuracy of IGE was 89.4%. Conclusions: The sensitivity of IGE for detecting deep myometrial invasion and cervical invasion in early-stage EC is too low to be used alone. Alternative methods including intraoperative frozen section analysis, preoperative three dimensional ultrasound, and preoperative magnetic resonance imaging should be strongly considered.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.1
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• pp.35-41
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• 2008

This study was undertaken to investigate the distribution of major histocompatibility complex class II positive (MHC II+) (HLA-DP-like) cells in the cow uterus (cervix, corpus and cornu uteri) and to compare these cells between the estrus and diestrus phases of the estrous cycle. Twenty-nine multiparous cows were used. Tissue samples from the middle of the cervix, the corpus and the right cornu were taken immediately after slaughter at the estrus or diestrus phase. Streptavidin-biotin peroxidase complex staining was used to detect MHC II+ cells. The number of MHC II+ cells per unit area of tissue was counted using image analysis software under a light microscope. Numerous MHC II+ cells were found in the endometrium (cervix, corpus and cornu uteri) in both estrus and diestrus. MHC II+ cells were found in the surface epithelium of the cervix uteri in diestrus, but in the corpus uteri in both estrus and diestrus and in the cornu uteri in estrus. MHC II+ cells were also found freely in the lumen of the glands and between the gland epithelia of the corpus and cornu uteri in both estrus and diestrus. There were also MHC II+ cells in the connective tissue of the myometrium and perimetrium (outside the endometrium) and around the blood vessels. Endothelial cells were frequently positive for MHC II staining. More MHC II+ cells were found in the endometrium than outside the endometrium in both estrus and diestrus (p<0.001). However, there was no difference in the numbers of positive cells between estrus and diestrus either in the endometrium or outside it. These results are the first evidence for HLA-DP-like MHC II+ cells in the bovine uterus. They indicate that antigen presentation by HLA-DP-like MHC II+ cells of the uterus is not influenced by hormonal status.

• Journal of Embryo Transfer
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• v.22 no.4
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• pp.229-234
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• 2007

This study was undertaken to determine the normal appearance of the postpartum uterine involution. Postpartum changes in uterine shape, architecture, echogenicity and diameter were monitored with ultrasonography in 8 Miniature Schnauzer dogs. Vaginal discharge was observed visually during the 3 weeks of postpartum. A large amount of viscous dark green discharge changed progressively to a small amount of transparent discharge. In the uterine shape, the transverse images were crescent or polygonal at the beginning, but became circular after 16 days. At postpartum day 24, the longitudinal images of placental and interplacental sites were similar to each other The echogenicity of uterine structure was clearly distinguishable among the hyperechoic serous membrane, hypochoic myometrium, hyperechoic endometrium, and anechoic uterine contents during the first week postpartum, but afterward the interluminal boundaries and echogenicity became obscure gradually. In addition, the anechoic substance of the endometrial cavity was not observed after postpartum day 28. In the uterine diameter, the diameter of placental sites decreased markedly from 24 mm at the first day postpartum to 13 mm at day 7, and the diameter of interplacental sites decreased from 15 mm at postpartum day 1 to 10 mm at day 7. At postpartum day 65, the uterus (6.4 mm) changed little and had a uniform homogenous echo, and thus it was confirmed that uterine involution was completed at that time in Miniature Schnauzer dogs.

• Development and Reproduction
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• v.24 no.3
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• pp.159-165
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• 2020

Previously, we reported adverse effects of low-dose nonylphenol (NP) exposure on the reproductive parameters of F1 female mice. In the present study we further investigated the pathohistological effect of NP exposure on the reproductive organs in F1 female mice. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 33 of F1 offspring for vaginal examination. Mice were sacrificed on PND 30 and the reproductive tissue weights were measured. The initial (at PND 21) body weights of the NP-50 group animals were significantly lower than those of control group animals, and the weight deficit were recovered when the terminal (PND 33) body weights were measured. Early vaginal opening was found in NP group animals (p<0.05). Pathohistological studies revealed that NP-treated F1 animals showed prominent increase in the ovarian follicle numbers (p<0.01), and decrease in the diameter of uterine myometrium (p<0.01), and increase in the diameter of luminal epithelium (p<0.05). The present study demonstrated that the subchronic low-dose NP exposure induced early beginning of puberty and pathohistological abnormalities in ovary and uterus of F1 mice. Further studies are needed to achieve a better understanding on the action mechanism of NP in pubertal onset and to find a way to avoid a hazardous situation provoked by NP exposure.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.3
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• pp.170-176
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• 2023

Objective: Autophagy is highly active in ovariectomized mice experiencing hormone deprivation, especially in the uterine mesenchyme. Autophagy is responsible for the turnover of vasoactive factors in the uterus, which was demonstrated in anti-Müllerian hormone receptor type 2 receptor (Amhr2)-Cre-driven autophagy-related gene 7 (Atg7) knockout (Amhr-Cre/Atg7^f/f mice). In that study, we uncovered a striking difference in the amount of sequestosome 1 (SQSTM1) accumulation between virgin mice and breeder mice with the same genotype. Herein, we aimed to determine whether repeated breeding changed the composition of mesenchymal cell populations in the uterine stroma. Methods: All female mice used in this study were of the same genotype. Atg7 was deleted by Amhr2 promoter-driven Cre recombinase in the uterine stroma and myometrium, except for a triangular stromal region on the mesometrial side. Amhr-Cre/Atg7^f/f female mice were divided into two groups: virgin mice with no mating history and aged between 11 and 12 months, and breeder mice with at least 6-month breeding cycles with multiple pregnancies and aged around 12 months. The uteri were used for Western blotting and immunofluorescence staining. Results: SQSTM1 accumulation, representing Atg7 deletion and halted autophagy, was much higher in virgin mice than in breeders. Breeders showed reduced accumulation of several vasoconstrictive factors, which are potential autophagy targets, in the uterus, suggesting that the uterine stroma was repopulated with autophagy-intact cells during repeated pregnancies. Conclusion: Multiple pregnancies seem to have improved the uterine environment by replacing autophagy-deficient cells with autophagy-intact cells, providing evidence of cell mixing.