• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.158-164
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• 2007

Uterine leiomyoma is the most common tumor in the female genital tract. Although the tumor is benign, it is a matter of paramount importance since it often causes profuse menstrual bleeding, pressure symptoms and infertility. Nevertheless, the etiology and pathophysiology of this abnormality remain poorly understood. The traditional definitive treatment for uterine leiomyomas is hysterectomy and, even today, symptomatic leiomyomas are the leading cause of hysterectomy in Korea. Clearly, the development of a safe, effective, and nonsurgical method of treatment for leiomyoma would be of great benefit to many women. This study demonstrated growth inhibition of uterine leiomyoma cells using Haeohyultang (HT). When human leiomyoma cells were treated with Haeohyultang, cells showed dose-dependent growth inhibitory effect. Cell growth was inhibited by over 40% as determined by both cell counts and MTS assay. Reduction of cellular viability as a consequence of exposure to Haeohyultang resulted from induction of apoptosis, as assessed by DNA fragmentation, PARP cleavage, caspase 9 and caspase 3 assay. Flow cytometry analysis with uterine leiomyoma cells demonstrated sub G1 cell cycle arrest after treatment with drug Haeohyultang. But, the expression levels of p27 and p21 were not changed in Haeohyultang treated cells compared with control. However, the expression levels of clAP1 were reduced by Haeohyultang compared with control. This reduction of clAP1 data means activation of the caspase family, and then induction of PARP cleavage and apoptosis. These results suggest that Haeohyultang may be potential therapeutic approach in the clinical management of uterine leiomyoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7129-7138
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• 2015

Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value ($45.9^{\circ}$) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.12
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• pp.1566-1577
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• 2010

Nandrolone, 19-nortestosterone, is a synthetic androgenic-anabolic steroid promoting muscle growth. Nandrolone is also present in pig meat and sera at non-negligible levels. A number of scientific reports have suggested a positive relationship between incidence of infertility and increased meat consumption in humans. The present study was designed to determine out the effect of feeding nandrolone on the testis of the male reproductive tract. Mixtures of food and nandrolone at different concentrations (0.005 ppm and 0.5 ppm) were supplied to pubertal male rats for 6 weeks. Body weight was recorded every week during the entire experimental period. At the end of the treatment, the testis, epididymis, and epididymal fat were collected and weighted. Sperm numbers in the caudal epididymis were counted. Differential gene or protein expression of steroidogenic enzymes in the testes among experimental groups was determined by semi-quantitative real-time PCR or western blotting analysis, respectively. Histological changes of the testis induced by nandrolone treatment were examined by hematoxylin and eosin staining. Immunohistochemical analysis was employed to detect changes in the localization of steroidogenic enzymes in the testes among experimental animals. There were no significant changes on body, testis, epididymis, and epididymal fat weights among experimental groups. A significant increase of caudal sperm number was found in the 0.5 ppm nandrolone-treated group. Histological examination of the testes noted a high frequency of germ cell sloughing in seminiferous tubules of 0.5 ppm nandrolone-treated rats. Even though transcript levels of $3{\beta}$-hydroxysteroid dehydrogenase (HSD) I, $17{\beta}$-HSD4, and $17{\alpha}$-hydroxylase were influenced by nandrolone treatments, protein levels of all molecules examined in the present study were not significantly affected. Immunohistochemical analysis showed no visible changes in the localization of steroidogenic enzymes in the testes among experimental groups. The current study showed that oral intake of nandrolone in male rats for 6 weeks did not cause significant damage to the testis. It is considered that a feeding effect of nandrolone on male fertility would not be remarkable.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.2
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• pp.141-151
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• 1998

Objectives: To determine whether the body weight, body mass index (BMI), and basal serum level of LH, FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S) are related to the ovarian response to clomiphene citrate (CC) in patients with polycystic ovarian syndrome (PCOS). Materials and Method: From January 1996 to June 1997, total 57 patients with PCOS were enrolled in the present study. Women who had other infertility factors were excluded from our study. The ovulation induction using CC was used in all patients. The patients were grouped into 50 mg group, 100 mg group, and 150 mg group according to their daily CC dose. The patients were also grouped to ovulatory and non-ovulatory group. The body weight, BMI, and basal serum level of LH, FSH, T, DHEA-S were measured in all patients on the 2nd or 3rd day of the menstrual cycle. Results were analysed with Student's t-test and Fisher's exact test. Results: The body weight and BMI of the nonovulating group were significantly higher than those of the ovulating group in all groups (50, 100, 150 mg of CC). However, there were no significant differences of the level of LH and FSH between ovulating and nonovulating groups in all CC groups (50, 100, 150 mg). The level of T of nonovulating group was significantly higher in 50 and 100 mg of CC groups, but not in 150 mg group. The level of DHEA-S of the non-ovulating group is significantly higher in 50 mg group, but not in 100 and 150 mg groups. Conclusion: The body weight and BMI could be useful predictors of ovarian response to CC in patients with PCOS, and basal T and DHEA-S also might be useful in cases of low-dose CC treatment.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.99-113
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• 2010

Objective: It has been recently reported that very small stem cells with pluripotency are detected in murine and human. The purposes of this study are to confirm whether very small putative stem cells (VSPSCs), which have the proper characteristics of stem cells as well as the expression of stem cell markers, are detected in human endometrium. Methods: The endometrial cells of 5 women, which were obtained by endometrial biopsy, were cultured for 2 weeks and were confirmed for the expressions of alkaline phosphatase, OCT-4 and CXCR4 by immunochemistry. Subsequently VSPSCs were separated by percoll density gradient method and were cultured. Also VSPSCs and their derived cells were confirmed for the expressions of OCT-4 and CXCR4. Results: The colonies, which is composed with VSPSCs less than 3 ${\mu}m$ and the 5~15 ${\mu}m$ sized hyperchromatic round cells, were detected in the endometrium of all of women and showed the strong expressions of alkaline phosphatase, OCT-4 and CXCR4. In culture after the separation of VSPSCs by percoll, these cells showed the morphological and functional characteristics of stem cells; self-renewal, colony formation, embryoid body-like formation and differential plasticity. VSPSCs formed gradually the 5~15 ${\mu}m$ sized hyperchromatic round cells and the 10~20 ${\mu}m$ sized sphere-shaped cells by cell-to-cell aggregation or cell fusion. Then these cells differentiated the various cells including fibroblast-like cells, nerve-like cells and endothelium-like cells. VSPSCs and their derived cells often showed the strong expressions of OCT-4 and CXCR4. Conclusion: VSPSCs less than 3 ${\mu}m$ and their derived cells are detected in human endometrium and these cells have the proper characteristics of stem cells and the expressions of stem cell markers as alkaline phosphatase, OCT-4 and CXCR4.

• Applied Microscopy
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• v.41 no.2
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• pp.109-116
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• 2011

Polycystic ovary syndrome (PCOS) is hormonal imbalance condition as the endocrine and metabolic disorder that induces the infertility and various complications in reproductive age women. Estradiol valerate (EV) is used hormone replacement therapy in menopausal women and is reported that excessive administration of EV induces the PCOS. Nerve growth factor (NGF) is the factor to regulate the survival and maturation of developing neuronal cell and is also synthesized in ovary. And NGF is overexpressed in EV-induced polycystic ovary (PCO) as previously reported. Therefore, this study examined the possibility of NGF as can be used the biological marker in diagnosis of PCOS, the hormonal imbalance condition, using PCO and CHO (chinese hamster ovarian) cell lines. The concentration of EV treatment is optimized a 1 mg as not influence on the proliferation of CHO cell but 2 mg and 3 mg of EV treatment have the inhibition effect at initial stage. The morphological change was not observed in CHO cell after dose dependent manner treatment of EV. Expression of NGF mRNA and protein is significantly increased at 30 min after EV treatment in CHO cells compared to that of control. And NGF protein expression is strongly increased in PCO tissue, which observed many follicular cysts compared to normal ovary tissue. Taken together, overexpression of NGF may be act as a molecule to induce an abnormal development of follicle, suggesting that NGF can be used as a biological marker in diagnosis of PCOS.

• Korean Journal of Animal Reproduction
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• v.24 no.4
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• pp.395-406
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• 2000

The present study was conducted to examine the developmental capacity of mouse oocytes within prenatal follicles cultured various concentrations of FSH and LH and the expression of cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17 $\alpha$ -hydroxylase (P450)$_{17{\alpha}}$ mRNA, as luteinization and atretic marker, in these culture conditions. In addition, we investigated the concentrations of progesterone and testosterone in culture medium. The developmental potential up to blastocyst of the oocytes grown in vitro was higher in the FSH alone (30.2%) and 10 $m\ell$U/$m\ell$ LH and 100 $m\ell$U/$m\ell$ FSH treated (28.0%) groups than in the 100 $m\ell$U/$m\ell$ LH and 100 $m\ell$U/$m\ell$ FSH treated group (22.0%). And the mean numbers of cell per blastocyst was higher in the FSH alone (50.9$\pm$26.1) and 10 $m\ell$U/$m\ell$ LH and 100 $m\ell$U/$m\ell$ FSH treated (51.0$\pm$21.1) groups when compared to the 100 $m\ell$U/$m\ell$ LH and 100 $m\ell$U/$m\ell$ FSH treated group (45.2$\pm$15.1). The expressions of P450scc and P450$_{17{\alpha}}$ mRNA in the oocyte -cumulus complexes were increased with increasing of LH concentration, and also the secretions of progesterone and testosterone were increased. Especially, in the 100 $m\ell$U/$m\ell$ LH and 100 $m\ell$U/$m\ell$ FSH treated group, the expression of P450scc and P450$_{17{\alpha}}$ were significantly increased, and the secretion of progesterone and testosterone were significantly increased. Therefore, these data show that gonadotrophins are essential for the in vitro culture of preantral follicles, but that increasing of LH concentration is reduced the developmental capacity of oocytes. The cause of these findings may be due to increasing of progesterone and testosterone secretion by the enhance of P450scc and P450$_{17{\alpha}}$ mRNA expressions, as markers of luteinization and atresia. Conclusively, this study suggest that supplementation of 100 $m\ell$U/$m\ell$ FSH or 10 $m\ell$U/$m\ell$ LH and 100 $m\ell$U/$m\ell$ FSH may be optimal condition for the culture of mouse pre antral follicles.