Yu, Jeong-Min;Yoo, Seong-Jin;Kim, Do-Rim;Youm, Mi-Young, Kim, Jee-Yun;Kang, Sung-Goo
Proceedings of the Korean Society of Embryo Transfer Conference
/
2002.11a
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pp.112-112
/
2002
Under normal conditions, women produce a single dominant follicle that participates in a single ovuation each menstrual cycle. But Polycystic ovary syndrome(PCOS) conditions, folliculogenesis does not proceed normally. This condition leads to the accumlation of large numbers of small graffian follicles in which the theca interstitial cells (TIC) produce abnormally large amounts of androgen. PCOS is probably the most common endocrine disorder, affecting women of reprodutive age with 5-10% prevalence estimate. Chronic anovulation, hyperandrogenism, hirsutism, obesity, infertility and polycystic ovaries are clinical hallmarks of women with PCOS. Its etiology remains unknown. To investigate the gene expression pattern of ovary in PCO-induced rat, we used cDNA expression analysis. Total RNA was extracted from the ovary of PCO-induced rat and reverse-transcribed in the presence of[$\alpha$$^{32}$P]-dATP Which were hybridized to Atlas$^{TM}$ Rat Toxicology 1.2 array (Clontech) representing approximately 1176 rat genes. We compared gene expression between ovary of pco-induced immature female rats and control. Differential gene expression profiles were revealed (LIFR-alpha, ADRA1A, Heat shock 90-kDa protein A, PDGFRA). Reverse transcription-polymerase chain reaction(RT-PCR) was used to validate the relative expression pattern obtained by the cDNA array. The precise relationship between the altered expression of genes and PCO is a matter of further investigation. This study was supported by Korea Science and Engineering Foundation(KOSEF)
Background : An increased frequency of reproductive endocrine disorders and polycystic ovary(PCO) has been reported in women with epilepsy. A possible role of the seizure disorder or, of the use of antiepileptic drugs(AEDs) has been suggested as the pathogenic mechanism. The objective of the present study was to assess the prevalence of reproductive endocrine disorders, such as PCO or menstrual abnormalities, in a series of women with epilepsy, examining the possible relationships of these disturbances with different epilepsy syndromes and AED treatment. Methods : Thirty epileptic women, all of reproductive age and none pubertal, pregnant, or lactating, were evaluated by clinical endocrinological assessment, and pelvic ultrasonography. Seven patients were on valproic acid(VPA), nineteen on carbamazepine(CBZ), and four on diphenylhydantoin(DPH) treatment, respectively. Results : Menstrual irregularity was observed in 8 women(26.7%), dysmenorrhea in 7(23.3%), and premenstrual syndrome in 1(3.3%). Ultrasonographic examination revealed that one women(3.3%) showed polycystic ovary, 4(13.3%) had ovarian cyst(s), and 2(6.7%) had uterine myoma, respectively. There was no difference in the prevalence of menstrual abnormalities or polycystic ovary according to the different preparations of AEDs. Conclusions : Data from this investigation suggest that, in Korean reproductive age women, the treatment of AEDs and the kind of medication may not have a significant effect on the prevalence of menstrual abnormalities or ultrasonographic polycystic ovary.
Purpose: This study was designed to investigate the effects of Cyperi Rhizoma (CR) on changes in weights morphological and histopathological observations in Polycystic Ovary(PCO) rats. Methods: PCO was induced by single intramuscular injection with EV(2mg) in female rats. Normal group(n=8) were injected with sesame oil and orally administrated distilled water for five weeks. PCO control group(n=8) were injected with EV and orally administrated distilled water for five weeks. CR treated group(n=8) were injected with EV and orally administrated CR for five weeks. Then we measured weight of body, ovaries. The histopathology changes of ovaries, and the expression of nerve growth factor(NGF) were also evaluated. Results: Single injection of EV induced suppression of weight gain, formation of cysts, increase of NGF expression. Oral administration of CR prevent suppression of weight gain shown in control group. In addition CR group showed upward tendency of ovarian size. Formation of cystic follicles induced by EV injection is suppressed by CR treatment. In additon, CR treatment lowered expression levels of nerve growth factor(NGF), which were elevated by induction of PCOS. Conclusion: These results suggest that CR can be used for patients with PCOS to prevent formation of cystic follicles and malfunction of ovary. And also suggest that the related mechanisms are involved in suppression of NGF expression.
Purpose: This study was designed to investigate the effects of Gwibi-Tang(GBT) on the polycystic ovary(PCO) induced by estradiol valerate(EV) in rats. Methods: PCO was induced by single intramuscular injection with EV(4mg) in female rats. Normal group(n=8) were injected with sesame oil and orally administrated distilled water for eight weeks. PCO control group(n=8) were injected with EV and orally administrated distilled water for eight weeks. GBT treated group(n=8) were injected with EV and orally administrated GBT for eight weeks. Then we measured weight of body, ovaries, adrenal glands, and uterus of rats. The histopathology changes of ovaries were also evaluated. The expression of nerve growth factor(NGF) was analyzed in the central nervous system, adrenal glands and ovaries by immunohistochemistry. And also CRF expression in median eminance of Rats were analyzed. Results: 1. The weight(g) of rats in GBT treated group($275{\pm}14$) was significantly increased(p<0.01) compared with control group($253{\pm}8$), 2. The weight(mg) of ovaries in GBT treated group($75.8{\pm}16.7$) was significantly increased(p<0.001) compared with control group($37.4{\pm}6.7$). 3. The number of mature follicles in GBT treated group($3.6{\pm}1.2$) was significantly increased(p<0.01) compared with control group($1.5{\pm}1.5$. 4. The number of atretic follicles in GBT treated group($8.0{\pm}3.1$) was significantly decreased(p<0.01) compared with control group($18.6{\pm}6.0$). 5. The number of cystic follicles in GBT treated group($0.5{\pm}0.5$) was significantly increased(p<0.01) compared with control group($2.3{\pm}1.3$). 6. The number of corpora lutea in GBT treated group($6.1{\pm}3.9$) was significantly increased(p<0.01) compared with control group($1.6{\pm}2.3$). 7. The expression of NGF-immunoreactive cells in the ovarian granulosa cells in GBT treated group was lesser observed than control group. Conclusion: From the above results, we concluded that Gwibi-Tang has inhibitory effect on the development of EV-induced polycystic ovary. And it's effect may be related with decreased NGF activities in the ovary.
Normal and abnormal follicular growth and steroidogenesis depend on gonadotropins as well as intraovarian peptides, which may mediate or potentiate gonadotropin action. Inhibin also affect follicular development and steroidogenesis and may play a role in dominant follicle selection and follicular atresia. Therefore, we studied the differences of serum inhibin, gonadotropin and androgen levels in the women with only the ultrasound findings and no disorder, and polycystic ovary (PCO) with ovulatory disturbance. We prospectively analysed forty-three women with PCO. The diagnosis of PCO was based on typical appearance of the ovaries on TVS. Twelve women with regular menstrual cycle and normal ovarian morphology were selected as control. Basal levels of inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol $(E_2)$, testosterone (T), androstenedione (ADD), dehydroepiandrosterone-sulfate (DS), prolactin and TSH in serum were determined. There were significant differences in basal LH levels and LH/FSH ratio between the control and the women with PCO. The basal levels of inhibin and $E_2$ in the oligo-amenorrheic PCO (N=34) were significantly higher than those in the control. There was higher negative correlation between the inhibin and T levels in the oligo-amenorrheic PCO, but, not in the regular cycling PCO. Also, there was higher positive correlation between the LH and T levels in the oligo-amenorrheic PCO, but not in the regular cycling PCO. These data presume that the initial event of PCO is elevated pituitary LH secretion. Elevated levels of LH may down-regulate LH receptors on granulosa cells and also cause hypertrophy of the thecal layer. High level of androgen secreted by the hypertrophied thecal layer may stimulate inhibin secretion from granulosa cells and can be converted to estrogen by extraovarian tissues and could serve to augment pituitary sensitivity to GnRH with a resultant secretion of more LH than FSH. Inhibin may inhibit FSH action on granulosa cell in the PCO follicle, impairing follicular development and dominant follicle selection resulted in ovulatory disturbance.
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.
Experimental induction of polycystic ovary (PCO) resembling some aspects of human PCO syndrome was produced using the long-acting compound estradiol valerate (EV). Our previous study on the role of Korean red ginseng total saponins (GTS) in a steroid-induced PCO rat model demonstrated that electro-acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In fact, the involvement of a neurogenic component in the pathology of PCO-related ovarian dysfunction is preceded by an increase in sympathetic outflow to the ovaries. In the present study, we tested the hypothesis that therapeutic GTS administration modulates sympathetic nerve activity in rats with PCO. This was done by analyzing NGF protein and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. EV injection resulted in significantly higher ovarian NGF mRNA expression in PCO rats compared to control rats, and PCO ovaries were counteracted by GTS administration with significantly lower expression of NGF mRNA compared to EV treated ovaries. However, NGF protein was unaffected in both EV and GTS treated ovaries compared to control rats. These results indicate that EV modulates the neurotrophic state of the ovaries, which may be a component of the pathological process by which EV induces cyst formation and anovulation in rodents.
In order to define the clinical characteristics of Korean women with polycystic ovary syndrome, clinical symptoms, biochemical features and ultrasonographic findings were determined in ninety PCO patients. Frequency of clinical manifestations were as follows:acne 42%, overweight 31 %, oily skin 14 %, hirsutism 10%. Relatively low frequencies of hirsutism is recognized in patients with Korean PCO syndrome. Mean(${\pm}$S.E.) of each hormone was:testosterone 1.18${\pm}$1.07ng/ml, LH 21.47${\pm}$${\pm}$2.6mIU/ml, FSH 7.26${\pm}$2.67mIU/ml, LH/FSH ratio 2.94${\pm}$1.29, prolactin 25.48${\pm}$46.33ng/ml, DHEA-S 333.78${\pm}$309.60ng/dl, 17-0HP 1.72${\pm}$1.74ng/ml. Mean 17-OHP after ACTH stimulation test was 5.07${\pm}$12.01ng/ml. Ultrasonographically measured mean ovarian volume were $11.02{\pm}5.92cm^3$ in right and $9.23{\pm}5.64cm^3$ in left and small sized multiple subcapsular follicular cysts were noted in 43 patients (47.9%) with PCO syndrome.
A form of polycystic ovary (PCO) resembling some aspects of the human PCO syndrome (PCOS) can be induced in rats by a single injection of estradiol valerate (EV). An increase in sympathetic outflow to the ovary precedes, by several weeks, the appearance of cysts, suggesting the involvement of a neurogenic component in the pathology of this ovarian dysfunction. To test the hypotheses that the change in sympathetic tone is related to an augmented production of hippocampal and/or ovarian nerve growth factor (NGF), and that this abnormally elevated production of NGF contributes to the induction of PCOS induced by EV. The animals were sacrificed after PCOS induction and the ovaries and hippocampus were sectioned and compared to the normal control. The expression of NGF was measured by immunohistochemical staining and Western blot analysis in the ovaries and hippocampus. EV-induced PCOS showed significant increase of ovarian NGF expression. Immunohistochemical expression of NGF was confined to the follicular cells and interstitial cells. Hippocampal NGF expression was not significantly changed. In conclusion EV-induced PCOS was related to the ovarian sympathetic activation which was mediated by NGF.
Objectives: This study was designed to investigate the effects of Yongdamsagantang on the polycystic ovary(PCO) induced by estradiol valerate(EV) in rats. Methods: After administrating Yongdamsagan-tang to PCO induced rats, we measured the weight of body, ovaries, adrenal glands, and uterus of rats. The observation through naked eye and histopathological observation of ovaries were evaluated. Also, the number of follicle and corpora lutea and content of androstenedione(ADD) and total estrogen were evaluated. The expressions of nerve growth factor(NGF) and corticotropin releasing factor(CRF) were analyzed by immunohistochemistry. The breeding rate and number of implantation with normal male rats were evaluated. Results: - The weight(mg) of ovaries in YST treated group($73.8{\pm}7.6$) was significantly increased(p<0.001) compared with control group($54.3{\pm}4.5$). - The number of mature follicles in YST treated group($7.3{\pm}2.4$) was significantly increased(p<0.01) compared with control group($3.5{\pm}1.2$). - The number of atretic follicles in YST treated group($9.0{\pm}1.5$) was significantly decreased(p<0.01) compared with control group($13.4{\pm}3.8$). - The number of cystic follicles in YST treated group($3.1{\pm}1.1$) was significantly decreased(p<0.01) compared with control group($6.0{\pm}2.0$). - The number of corpora lutea in YST treated group($3.8{\pm}2.1$) was significantly increased(p<0.001) compared with control group($0.3{\pm}0.7$). - The expression of NGF-immunoreactive cells in the ovarian granulosa cells in YST treated group was lesser observed than control group. - The expression of NGF-immunoreactive cells in the adrenal cortex in YST treated group was lesser observed than control group. - The breeding rate in YST treated group(100 %) was significantly increased (p<0.05) compared with control group(50 %). - The number of implantation in YST treated group($6.4{\pm}4.7$) was significantly increased(p<0.05) compared with control group($1.4{\pm}2.6$). Conclusions: We concluded that Yongdamsagan-tang activates the maturation of follicles, normal ovulation, breeding rate and number of implantation. Therefore, this may be effective for the treatment of anovulation, amenorrhea and sterility of PCOS patients.
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