• Journal of Korean Medicine Rehabilitation
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• v.30 no.1
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• pp.1-12
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• 2020

Objectives Depletion of ovarian function after menopause in women induces estrogen deficiency leading to increased fat and decreased muscle mass. In this study, we examined the effect of herbal medicines by measuring hormone expression in muscle tissue of estrogen-deficient rats induced by ovariectomy. Methods Ovariectomy was performed to induce estrogen deficiency, and mice were given herbal prescription (HP) for 6 weeks. Estrogen-deficient rats were divided into two groups: one group (HPH) which were orally administered HP 200 mg/kg and the other group (HPL) administered HP 40 mg/kg. Weight changes in both groups were measured using polymerase chain reaction (PCR). After extraction of the femoral muscles in mice, the expression of the leptin, lipoprotein lipase (LPL), diacyl glycerol acyltransferase (DGAT)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, NADH dehydrogenase (NDH), farnesyl diphosphate farnesyltransferase (FDFT)1, lanosterol synthase (LSS), phosphatidylethanolamine N-methyltransferase (PEMT), and peroxiredoxin (Prdx6) were measured using PCR. Results HP increased the expression of leptin, LPL, DGAT1, PGC-1α, NDH, FDFT1, LSS, PEMT, and Prdx6. HP affects body fat metabolism and is effective in improving menopausal obesity and obesity complications caused by estrogen deficiency. However, HP does not affect the expression of tumor necrosis factor-α and 3-hydroxy-3-methylglutaryl-CoA reductase, and thus will not be effective in obesity-related metabolic diseases. Conclusions HP is thought to inhibit weight gain by regulating hormone expression related to glucose metabolism and lipid metabolism in muscle tissue of estrogen-deficient rats.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.4
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• pp.207-214
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• 2016

Objective: This study aimed to determine the threshold of $anti-M{\ddot{u}}llerian$ hormone (AMH) as predictor of follicular growth failure in polycystic ovary syndrome (PCOS) patients treated with clomiphene citrate (CC). Methods: Fifty female subjects with PCOS were recruited and divided into two groups based on successful and unsuccessful follicular growth. Related variables such as age, infertility duration, cigarette smoking, use of Moslem hijab, sunlight exposure, fiber intake, body mass index, waist circumference, AMH level, 25-hydroxy vitamin D level, and growth of dominant follicles were obtained, assessed, and statistically analyzed. Results: The AMH levels of patients with successful follicular growth were significantly lower (p= 0.001) than those with unsuccessful follicular growth ($6.10{\pm}3.52$ vs. $10.43{\pm}4.78ng/mL$). A higher volume of fiber intake was also observed in the successful follicular growth group compared to unsuccessful follicular growth group (p= 0.001). Our study found the probability of successful follicle growth was a function of AMH level and the amount of fiber intake, expressed as Y =-2.35+($-0.312{\times}AMH\;level$)+($0.464{\times}fiber\;intake$) (area under the curve, 0.88; 95% confidence interval, 0.79-0.98; p< 0.001). Conclusion: The optimal threshold of AMH level in predicting the failure of follicle growth in patients with PCOS treated with CC was 8.58 ng/mL.

• Genomics & Informatics
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• v.3 no.4
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• pp.154-158
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• 2005

Germ-line mutations of the BRCA1 gene confer an increased risk for breast and ovarian cancers. BRCA1 in female cells is directly related with the maintenance of the inactive X chromosome (Xi). The effect by the loss of the BRCA1 function on the X chromosome gene expression remains unclear in cancer cells. We attempted to investigate the expression pattern of the X-linked genes by performing BRCA1 knockdown via RNA interference in the MCF7 breast cancer cell line. The transcriptional and translational levels of BRCA1 were decreased over 95% in the MCF7 cells after BRCA1 knockdown. The expression patterns of one hundred ninety X-linked genes were profiled by the X chromosome-specific cDNA arrays. A total of seven percent of the X-linked genes (14/190) were aberrantly expressed by over 2-fold in the MCF7-BRCA1 knockdown cells, which contained two up-regulated genes (2/190, 1 %) and 12 down-regulated genes (12/190, 6.3%). It is interesting that 72% of the aberrantly expressed X-linked genes were located on the Xq (10/14,) region. Our data suggests that BRCA1 may not be important to maintain X chromosome inactivation in cancer because the BRCA1 knockdown did increase the expression of the only one percent of X-linked genes in the human breast cancer cells.

• Reproductive and Developmental Biology
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• v.42 no.2
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• pp.7-12
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• 2018

In this review, we have tried to summarize the evidence and molecular characterization indicating that $20{\alpha}$-hydroxysteroid dehydrogenase ($20{\alpha}$-HSD) is a group of the aldo-keto reductase (AKR) family, and it plays roles in the modulation and regulation of steroid hormones. This enzyme plays a critical role in the regulation of luteal function in female mammals. We have studied the molecular expression and regulation of $20{\alpha}$-HSD in cows, pigs, deer, and monkeys. The specific antibody against bovine $20{\alpha}$-HSD was generated in a rabbit immunized with the purified recombinant protein. The mRNA expression levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. The mRNA was also specifically detected in the placental and ovarian tissues during pregnancy. The $20{\alpha}$-HSD protein was intensively localized in the large luteal cells and placental cytotrophoblast villus, glandular epithelial cells of the endometrium, syncytiotrophoblast of the placenta, the isthmus cells of the oviduct, and the basal part of the primary chorionic villi and chorionic stem villus of the placenta and large luteal cells of the CL in many mammalian species. Further studies are needed to determine the functional significance of the $20{\alpha}$-HSD molecule during ovulation, pregnancy, and parturition. This article will review how fundamental information of these enzymes can be exploited for a better understanding of the reproductive organs during ovulation and pregnancy.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.3
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• pp.192-213
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• 2019

Objectives: The purpose of this study is to analyze the domestic study trends of pharmacopuncture therapy on obstetrics and gynecological diseases in Korean literature, through reviewing the clinical and experimental studies. Methods: We searched for clinical and experimental studies using pharmacopuncture therapy on obstetrics and gynecological diseases, published from January 2000 to May 2019, through 5 Korean databases. The study design, target disease, type of pharmacopuncture, method of intervention, and study results were analyzed. Results: 36 experimental studies and 15 clinical studies were finally included according to inclusion and exclusion criteria. In experimental studies, there were 12 studies about postmenopausal osteoporosis, 9 studies about obesity, 4 studies about endometriosis, 3 studies about hemostatic effects and analgesic anticoagulative effects, 2 studies about ovarian function, and analgesic antiphlogistic anticoagulative effects, and 1 study about menopausal symptoms. In clinical studies, there were 3 studies about obesity, postpartum disorders, dysmenorrhea, and women's urologic disease, and 1 study about menopausal symptoms, atypical squamous cells of undetermined significance (ASCUS) and breast cancer. Various types of pharmacopuncture have been proved to have a therapeutic effect in each of those obstetrics and gynecological diseases. Conclusions: This study indicates that pharmacopuncture therapy could be a good treatment for obstetrics and gynecological diseases. However, more well-designed and high-quality clinical researches are needed in further studies, to prove the effectiveness and safety of pharmacopuncture therapy.

• Korean Journal of Agricultural Science
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• v.48 no.1
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• pp.163-170
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• 2021

Bacterial infections in the female reproductive tract negatively affect ovarian function, follicular development, and embryo development, leading to the eventual failure of fertilization. Moreover, bacterial lipopolysaccharides (LPS) can interfere with the immune system and reproductive system of the host animal. Therefore, this study examined the effect of LPS on the in vitro maturation (IVM) of pig oocytes. Oocytes were matured in TCM199 medium in the presence of varying concentrations of LPS (0 - 50 ㎍·mL^-1). The maturation rate, cortical granules (CGs) migration, and chromosome alignment were subsequently evaluated during the meiotic development of the oocytes. We observed a dose-dependent and significant decrease in the metaphase II (MII) rate with increasing concentrations of LPS (97.6% control [0 ㎍·mL^-1 LPS] vs. 10.4-74.9% LPS [1 - 50 ㎍·mL^-1], p < 0.05). In addition, compared to the control oocytes without LPS, higher levels of abnormal CGs distribution (18.1 - 50.0% LPS vs. 0% control), chromosome/spindle alignment (20.3 - 56.7% LPS vs. 0% control), and intracellular ROS generation were observed in oocytes matured with LPS (p < 0.05). Nitrite levels were also increased in the maturation medium derived from the oocytes matured with LPS (p < 0.05). These results indicate that LPS induces oxidative stress during IVM and affects oocyte maturation, including CGs migration and chromosome alignment of pig oocytes.

• Development and Reproduction
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• v.27 no.4
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• pp.185-193
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• 2023

Although increasing evidence of cause-and-effect relationship between BPA exposure and female reproductive disorders have been suggested through many studies, the precise biochemical and molecular mechanism(s) by which BPA interferes with steroidogenesis in the ovarian cells still remain unclear. Therefore, the purpose of this study was to discover the steroidogenic biomarker(s) associated with BPA treatment in human granulosa cell line, KGN. In this study, our results obtained via the analysis of steroidogenesis-related protein expression in KGN cells using quantitative polymerase chain reaction (qPCR) and western blot analyses revealed that the expression levels of steroidogenic acute regulatory (StAR) and aromatase decreased considerably and gradually after BPA treatment in a dose-dependent manner under BPA treatment. Further, remarkable decreases in their expression levels at the cellular levels were also confirmed via immunocytochemistry, and subsequent StAR and aromatase mRNA expression levels showed profiles similar to those observed for their proteins, i.e., both StAR and aromatase mRNA expression levels were significantly decreased under BPA treatment at concentrations ≥0.1 μM. We observed that follicle stimulating hormone upregulated StAR and aromatase protein expression levels; however, this effect was suppressed in the presence of BPA. Regarding the steroidogenic effects of BPA on KGN cells, controversies remain regarding the ultimate outcomes. Nevertheless, we believe that the results here presented imply that KGN cells have a good cellular and steroidogenic machinery for evaluating endocrine disruption. Therefore, StAR and aromatase could be stable and sensitive biomarkers in KGN cells for the cellular screening of the potential risk posed by exogenous and environmental chemicals to female reproductive (endocrine) function.

• Development and Reproduction
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• v.6 no.2
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• pp.123-129
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• 2002

Leptin, a product of the obese gene, is associated not only with obesity but also with female reproductive function, but it has not yet been ascertained whether leptin acts directly on the ovary or indirectly via the hypothalamus-pituitary pathway. Therefore, the object of this study was to investigate the expession of leptin and its receptor in the rat ovary by immunohistochemistry and RT-PCR during the estrous cycle. Immunohistochemistry results showed that leptin was stained in the theca cells and in part of granulosa cells in atretic follicles, whereas leptin receptor was localized in the interstitial cells and ova in preantral follicies. In particular, leptin and its receptor in atretic follicles displayed more intensive staining compared to those in normal follicles. During the estrous cycle, the mRNA expression of leptin and its receptor in the ovary was detected by RT-PCR and estradiol, progesterone, and leptin levels in the serum was measured by ELISA. The leptin level in the serum on metestrous phase was significantly higher than that on estrous phase. Similar to leptin level, progesterone level increased on metestrous phase. Leptin mRNA was not detected throughout the estrous cycle, whereas leptin receptor mRNA was expressed on all phases of estrous cycle excepting the diestrous phase. These results suggest that leptin might be directly involved in the regulation of ovarian function in rat.

• Journal of Life Science
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• v.26 no.7
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• pp.826-834
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• 2016

The present investigation was undertaken to examine the effectiveness of the combination treatment of an Hsp90 inhibitor and a SIRT1 inhibitor on suppressing the growth of chemo-resistant human cancer cells. We showed that inhibition of SIRT1 effectively potentiated the cytotoxicity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) and reversed Hsp90 inhibitor resistance in multidrug-resistant (MDR) human ovarian HeyA8-MDR cells. Amurensin G, a potent natural SIRT1 inhibitor, enhanced Hsp90 inhibitor-mediated abrogation of the Hsp90 chaperone function and accelerated degradation of mutated p53 (mut p53), an Hsp90 client protein, by up-regulation of ubiquitin ligase CHIP. Knock-down of CHIP significantly attenuated amurensin G-induced mut p53 degradation. Down-regulation of mut p53 reduced the expression of heat shock factor1 (HSF1)/heat shock proteins (Hsps), a major cause of Hsp90 inhibitor resistance, which led to sensitization of the MDR cells to the Hsp90 inhibitor by the SIRT1 inhibitor. Amurensin G potentiated cytotoxicity of the Hsp90 inhibitor in HeyA8-MDR cells through suppression of 17-AAG-induced Hsp70 and Hsp27 induction via down-regulation of mut p53/HSF1, and it caused activation of PARP and inhibition of Bcl-2. Our data suggests that SIRT1 inhibitors could be used to sensitize MDR cells to Hsp90 inhibitors, possibly through suppression of the mut p53/HSF1-dependent pathway, and a novel mut p53-directed action of SIRT1 inhibition could effectively prevent mut p53 accumulation in MDR cells.

• The Journal of Korean Society for Radiation Therapy
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• v.33
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• pp.145-153
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• 2021

Purpose: The purpose of this study is to evaluate the ovarian dose during radiation therapy for breast cancer in women of childbearing age through an experiment. The ovarian dose is evaluated by comparing and analyzing between the calculated dose in the treatment planning system according to the treatment technique and the measured dose using a thermoluminescence dosimeter (TLD). The clinical usefulness of lead (Pb) apron is investigated through dose analysis according to whether or not it is used. Materials and Methods: Rando humanoid phantom was used for measurement, and wedge filter radiation therapy, 3D conformal radiation therapy, and intensity modulated radiation therapy were used as treatment techniques. A treatment plan was established so that 95% of the prescribed dose could be delivered to the right breast of the Rando humanoid phantom 3D image obtained using the CT simulator. TLD was inserted into the surface and depth of the virtual ovary of the Rando hunmanoid phantom and irradiated with radiation. The measurement location was the center of treatment and the point moved 2 cm to the opposite breast from the center of the Rando hunmanoid phantom, 5cm, 10cm, 12.5cm, 15cm, 17.5cm, 20cm from the boundary of the right breast to the center of treatment and downward, and the surface and depth of the right ovary. Measurements were made at a total of 9 central points. In the dose comparison of treatment planning systems, two wedge filter treatment techniques, three-dimensional conformal radiotherapy, and intensity-modulated radiation therapy were established and compared. Treatments were compared, and dose measurements according to the use of lead apron were compared and analyzed in intensity-modulated radiation therapy. The measured value was calculated by averaging three TLD values for each point and converting using the TLD calibration value, which was calculated as the point dose mean value. In order to compare the treatment plan value with the actual measured value, the absolute dose value was measured and compared at each point (%Diff). Results: At Point A, the center of treatment, a maximum of 201.7cGy was obtained in the treatment planning system, and a maximum of 200.6cGy was obtained in the TLD. In all treatment planning systems, 0cGy was calculated from Point G, which is a point 17.5cm downward from the breast interface. As a result of TLD, a maximum of 2.6cGy was obtained at Point G, and a maximum of 0.9cGy was obtained at Point J, which is the ovarian dose, and the absolute dose was 0.3%~1.3%. The difference in dose according to the use of lead aprons was from a maximum of 2.1cGy to a minimum of 0.1cGy, and the %Diff value was 0.1%~1.1%. Conclusion: In the treatment planning system, the difference in dose according to the three treatment plans did not show a significant difference from 0.85% to 2.45%. In the ovary, the difference between the Rando humanoid phantom's treatment planning system and the actual measured dose was within 0.9%, and the actual measured dose was slightly higher. This did not accurately reflect the effect of scattered radiation in the treatment planning system, and it is thought that the dose of scattered radiation and the dose taken by CBCT with TLD inserted were reflected in the actual measurement. In dosimetry according to the with or without a lead apron, when a lead apron was used, the closer the distance from the treatment range, the more effective the shielding was. Although it is not clinically appropriate for pregnancy or artificial insemination during radiotherapy, the dose irradiated to the ovaries during treatment is not expected to significantly affect the reproductive function of women of childbearing age after radiotherapy. However, since women of childbearing age have constant anxiety, it is thought that psychological stability can be promoted by presenting the data from this study.