• 한국발생생물학회지:발생과생식
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• 제10권2호
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• pp.147-154
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• 2006

전세계적으로 매년 대량생산되는 프탈레이트(phthalate)류 물질은 플라스틱처럼 다양한 생활용품의 원료로 사용되기 때문에 인간에 대한 노출 정도가 매우 높은 산업 물질이다. 대표적으로 di(2-ethyl hexyl)phthalate(DEHP)와 그 활성 대사물인 monoethyl hexyl phthalate(MEHP)가 내분비계 장애물질(endocrine disruptor)로 작용하여 인간과 실험 동물의 생식계를 교란한다는 증거들이 급속히 축적되고 있다. 본 연구는 DEHP가 암컷 흰쥐의 사춘기 개시와 이와 관련된 생식 지표들의 변화에 미치는 효과를 조사한 것이다. 생후 25 일부터 corn oil 또는 DEHP(100mg/kg/day i.p.)를 사춘기 개시의 지표인 질구 개방(vaginal opening, VO)이 일어나는 날까지 투여하였다. 다음 날 희생시킨 후 난소와 자궁의 외양과 조직 무게를 측정하여 DEHP가 이들 조직에서의 세포증식에 미치는 효과를 조사하였고, 현미경 관찰을 통해 해부학적인 변화 양상을 조사하였다. 또한 혈액내의 LH 수준을 방사면역측정법(RIA)로 측정하였다. 자궁 성숙의 지표인 프로게스테론 수용체(PR) 발현 양상은 정량적인 RT-PCR로 확인하였다. 결과로, DEHP 투여에 의해 질구 개방이 지연됨을 확인하였다($35.3{\pm}0.7\;day$ in control group vs $37.3{\pm}0.7\;day$ in DEHP group, p<0.05). 흥미롭게도, 첫번째 주사 다음 날(p<0.05)부터 이후 마지막 주사 날(p<0.01)까지 DEHP 군의 체중이 대조군에 비해 유의하게 낮음을 관찰하였다. 난소와 자궁의 크기와 무게, 그리고 혈중 LH 수준도 대조군에 비해 DEHP 군에서 유의하게 감소하였다. 질구 개방이 일어난 대조군의 난소에서는 성숙의 지표인 그라프 난포(Graafian follicle)와 황체가 관찰되었으나 DEHP 군의 난소에서는 미성숙한 1차, 2차 난포 그리고 작은 퇴화 난포(atretic follicle)들만이 다수 관찰되었다. 자궁의 경우도 대조군에서는 내막층과 근막층은 물론 상피층까지 잘 발달된 과다 성장 상태와 함께 분비선 수의 증가가 나타났으나 DEHP 군에서는 모든 세포층의 발달이 미약한 상태였다. 이러한 결과는 DEHP가 과립세포에서의 에스트로겐 합성 분비에 억제적 효과를 나타내는 것에 기인하는 것으로 보인다. RT-PCR 결과 난소(p<0.05)와 자궁(p<0.01)에서의 PR mRNA 수준은 DEHP 투여에 의해 유의한 발현 감소가 나타났다. 결론적으로, 본 연구는 사춘기 전 특정 시기에 단기적인 DEHP 투여에 의해 암컷 흰쥐의 생식계 활성화가 억제되고, 그 결과 사춘기가 지연될 수 있음을 시사한다.

• Clinical and Experimental Reproductive Medicine
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• 제28권3호
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• pp.225-233
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• 2001

Objective : To evaluate the efficacy of low-dose aspirin on IVF outcome and endometrium in patients undergoing IVF-ET. Materials and Methods : From February, 2001 to Jun, 2001, 60 infertile patients were randomly divided into study group (28 cycles) and control group (32 cycles). The study group received a daily oral dose of 25 mg of aspirin for at least 2 weeks from first visiting day. Controlled ovarian hyperstimulation was initiated in all patients with the GnRH agonist starting in the midluteal phase of the previous cycle. Results: There were no significant differences in age of the patients, basal serum E2, LH, FSH level and endometrial thickness among two groups. There were no statistically significant differences between the study group and the control group respectively in dosage ($26.5{\pm}4.8$ vs $26.2{\pm}5.3$ amples) and duration ($10.4{\pm}4.2$ vs $9.8{\pm}5.3$ days) of gonadotropin administration, serum E2 level on the hCG administration day ($1823{\pm}342$ vs $1854{\pm}543$), LH ($14.5{\pm}2.7$ vs $14.8{\pm}3.1$), FSH ($16.7{\pm}3.4$ vs $18.3{\pm}4.7$), the number of follicles > 15 mm ($13.2{\pm}6.3$ vs $12.8{\pm}5.9$), the number of oocytes retrieved ($9.2{\pm}2.4$ vs $8.4{\pm}1.7$), the number of embryos transferred ($4.7{\pm}2.0$ vs $4.7{\pm}2.0$), fertilization rate (68.4% vs 64.5%), implantation rate (21.3% vs 17.6%), and clinical pregnancy rate (28.4% vs 26.2%). The endometrial thickness and the percentage of endometrial trilaminar pattern on hCG day were significantly higher in study group than control group ($12.9{\pm}3.7mm$ vs $10.4{\pm}2.8mm$, 78.3% vs 64.5%). Conclusion: Many reports suggest that low-dose aspirin improve ovarian response, implantation rate, fertilization rate, implantation rate, and pregnancy rate by increasing the blood flow, but we couldn't prove the significant effect of low-dose aspirin on the IVF outcome except on endometrium. This may be affected by dose of aspirin, duration, and number of patients studied. This trial is small, so our results highlight the need for a large randomized controlled trial to identify the effect of low-dose as pirin on IVF-ET outcome.

• Toxicological Research
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• 제33권3호
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• pp.255-263
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• 2017

Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the $14^{th}$ day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

• Fisheries and Aquatic Sciences
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• 제24권10호
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• pp.330-339
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• 2021

Oyster (Crassostrea gigas) is a marine bivalve mollusk widely distributed in coastal areas, and have been long widely used in industrial resources. Several studies demonstrated that fermented oyster (FO) extract attribute to bone health, but whether administration of FO play as an endocrine disruptor has not been studied. Therefore, in the present study, we investigated the effect of FO on the endocrine system in vitro and in vivo. As the results of the competitive estrogen receptor (ER) and androgen receptor (AR) binding affinities, FO was not combined with ER-α, ER-β, and AR. However, 17β-estradiol and testosterone, used as positive control, were interacted with ER and AR, respectively. Meanwhile, oral administration of 100 mg/kg and 200 mg/kg of FO doesn't have any harmful effect on the body weight, androgen-dependent sex accessory organs, estrogen-dependent-sex accessory organs, kidney, and liver in immature rats. In addition, FO supplementation has no effect on the serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and 17β-estradiol. However, the relative weight of androgen- and estrogen-dependent organs were significantly increased by subcutaneously injection of 4.0 mg/kg of testosterone propionate (TP) and by orally administration of 1.0 ㎍ of 17α-ethynyl estradiol (EE) in immature male and female rats, respectively. Furthermore, TP and EE administration markedly decreased the serum LH and FSH levels, which are similar those of mature Sprague-Dawley (SD) rat. Furthermore, the testosterone and 17β-estradiol levels were significantly enhanced in TP and EE-treated immature rats. Taken together, our findings showed that FO does not interact with ER and AR, suggesting consequentially FO does not play as a ligand for ER and AR. Furthermore, oral administration of FO did not act as an endocrine disruptor including androgenic activity, estrogenic activity, and abnormal levels of sex hormone, indicating FO may ensure the safety on endocrine system to develop dietary supplement for bone health.

• 한국융합학회논문지
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• 제13권3호
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• pp.337-343
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• 2022

본 연구는 다낭난소증후군 여성의 불안, 우울, 스트레스를 평가하고, 발병 위험인자에 대하여 살펴보고자, 다낭난소증후군 여성을 대상으로 Beck's 우울증(BDI) 및 우울 불안 스트레스 척도(DASS) 설문을 시행하였고, 항뮐러리안호르몬(AMH), 총 테스토스테론, 황체형성호르몬(LH), 난포자극호르몬(FSH), 에스트라디올(E2), 지질대사검사 및 당부하검사(OGTT)를 시행 후 분석하였다. 설문지를 완전히 작성하여 회수된 52명의 환자군과 29명의 건강한 가임기 여성 대조군을 분석하였다. 다낭난소증후군 환자 중 BDI>13점, DASS>10점인 우울증 38.5 %, DASS>8점인 불안 23.1 %, DASS>15점인 스트레스 30.8 %로 대조군에 비해 유의하게 높았다. 총 테스토스테론, LH 및 AMH는 우울증 및 스트레스와 유의한 상관관계를 보였고, 체중 및 체질량지수도 우울증과 유의한 상관관계를 보였다. 당뇨병과 고지혈증으로 진단된 여성에서 우울증과 스트레스가 높았다. 다낭난소증후군 여성은 우울증, 불안 및 스트레스에 더 취약한 것으로 나타나, 조기진단과 치료가 중요하다.

• Clinical and Experimental Reproductive Medicine
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• 제32권1호
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• pp.9-16
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• 2005

Objective: This study was performed to evaluate the effect of isoflavone supplementation on hormone levels, lipid profiles and total antioxidant status in patients with polycystic ovary syndrome. Methods: Total 11 women with polycystic ovary syndrome were supplemented daily with 150mg of isoflavone for 6 months. Blood samples were collected 0, 3, and 6 months after supplement of isoflavone for analysis of LH, FSH, E2, testosterone, free testosterone, SHBG levels, serum lipid profiles, and total antioxidant status (TAS). Results: After 6 months isoflavone supplementation, the hormone levels did not change significantly. Serum lipid profiles did not show any significant change in total cholesterol, LDL-cholesterol, triglyceride, lipoprotein(a), and free fatty acid levels. However, there was significant increase in HDL-cholesterol (p<0.05) for 3 months. Total antioxidant status was increased significantly after isoflavone supplementation for 6 months (p<0.05). Conclusion: Isoflavone supplementation showed positive effects on the HDL-cholesterol and total antioxidant status. it is implicated that isoflavone supplementation will may have a effect on cardiovascular disease in patients with polycystic ovary syndrome.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVI)
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• pp.37-37
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• 2005

Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone consisting of non-covalently linked two subunits, the ${\alpha}$ and ${\beta}$ subunit. It has been used as a infertility drug for ovulation to mimic luteinizing hormone $(LH).^{1)}$ A stable cell line was established by transfection of Rc/CMV-i-dhfr-hCG, expression vector containing hCG ${\alpha}-$ and ${\beta}-genes$, into dihydrofolate reductase-deficient CHO cells and subesquent methotrexate-mediated gene amplification. Anchorage-dependent CHO cells were adapted into a serum-free and/or animal component-free suspension medium through gradual serum weaning for the hCG production. The established cell line showed typical morphological characteristics and growth profile of CHO cells, and could produce FSH with passage-to-passage consistency. The high density perfusion culture of the CHO cells was carried out in Celligen Plus bioreactor equipped with a spin-filter as a internal cell retention device. The cell density reached up to $>1x10^{7}$ cells/ml in less than 7 days and a perfusion-control strategy based on cellular consumption rates of glucose was $established.^{2)}$ Biologically active recombinant hCG was purified by a series of chromatographic steps including anion exchange chromatography and hydrophobic interaction chromatography to homogeneity. The highly purified recombinant hCG was characterized for physicochemical, immunological and biological properties.

• 대한수의학회지
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• 제42권3호
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• pp.299-308
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• 2002

The purpose of this morphometric study was to obtain detailed quantitative information on all cell types in the testis interstitium of Korean ring-necked pheasants combined with data on changes in the steroidogenic function of the testis during the breeding and nonbreeding seasons. Animals collected during the breeding season, testis weights, sperm production, serum testosterone levels, leuteinizing hormone-stimulated testosterone secretion, and the length of the seminiferous tubules were significantly (p < 0.05) increased as compared to the nonbreeding season. Seminiferous tubules occupied 93.25% of testis volume in the breeding season. Leydig cells constituted 0.82% of the testicular volume. The mean volume of an Leydig cell was $1039{\mu}m^3$, and each testis contained about 24.53 million Leydig cells. Testes of the pheasants during the nonbreeding season displayed a 98% reduction in testis volume that was associated with a decrease in the absolute volume of seminiferous tubules (98% reduction), tubular lumen(100%), interstitium(90%), blood vessels(84%), lymphatic spaces(97%), Leydig cells(79%), mesenchymal cells(51%), and myoid cells(61%). The number of Leydig cells, mesenchymal cells, myoid cells per testis in the breeding season was higher (p < 0.05) than in the nonbreeding season. Although the average volume of a Leydig cell was 74% lower in the nonbreeding season, the average volume of a myoid and mesenchymal cell remained unchanged. These results demonstrate that there are a striking differences in the testicular structure of the Korean ring-necked pheasant in the breeding and nonbreeding seasons. Every structural parameter of the Leydig cell was pasitively correlated with both serum and LH-stimulated secretion concentrations of testosterone. Correlation of changes in hormonal status with morphometric alterations of all Leydig cell suggests that the Korean-ring necked pheasant may be used as a model to study structure-function relations in the avian testis.

• Clinical and Experimental Reproductive Medicine
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• 제21권1호
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• pp.83-88
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• 1994

This study was designed to investigate the relationship between insulin resistance and obesity in the pathogenesis of polycystic ovarian syndrome(PCO). Twenty-two women with PCO, of whom thirteen were non-obese with body mass index(BMI, kg/$m^2$) of <25 and nine were obese with BMI${\geq}$25 were studied. Eight non-obese control women and seven obese control women were studied. Serum concentrations of testosterone, lutenizing hormone(LH)/follicle-stimulating hormone(FSH) ratio, and insulin-like growth factor I (IGF-I) were found to be significantly higher(P<0.05) in PCO women compared with control women, which clearly is not related to obesity. Serum glucose, insulin, and C-peptide levels were measured during a 2-hour oral glucose tolerance test(OGTT). Non-obese and obese women with PCO both(P<0.05) compared with control women demonstrated significant hyperinsulinemia after OGTT. The degree of hyperinsulinemia was found to be significantly higher in the obese women with PCO compared with the non-obese women with PCO. We concluded that obesity may contribute to hyperinsulinemia, however may not playa central role in the pathogenesis of PCO.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3167-3171
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• 2016

Prostate cancer (PCa) is one of the most common diseases in men. It is important to assess prognostic factors and whether high cortisol levels and complex hormonal interactions could be responsible for PCa development. We evaluated the relationship between cortisol, leptin and estrogens in 141 men, 71 with PCa and the remaining 70 constituting a low risk group (LRG). They were recruited for this study from a total of 2906 middle-aged men (ages 45-70 years) who completed an evaluation for prostatic diseases at the Urology Division, Hospital de Clínicas "$Jos{\acute{e}}$ de San $Mart{\acute{i}}n$", University of Buenos Aires, in May 2009. In this cross sectional study, cortisol, PSA, total-testosterone, free-testosterone, bioavailable testosterone, LH and estradiol were measured in serum. We observed increased cortisol levels in PCa patients as compared to LRG cases (p=0.004,). Leptin and estradiol levels were also higher in PCa patients (p=0.048; p<0.0001, respectively). Logistic regression analysis indicated that serum cortisol (OR: 1.110 (95% CI 1.016-1.213), p=0.022), estradiol (OR: 1.044 (95% CI 1.008-1.081), p=0.016) and leptin (OR: 1.248 (95% CI 1.048-1.487), p=0.013) explained 27% of the variance of dependent variables, even after adjusting for age, smoking, BMI and waist circumference. We found increased cortisol levels in PCa patients as compared to LRG, as well as an altered circulating hormonal profile.