인간 난소의 노화와 Mitochondrial DNA 결손의 상관관계에 대한 연구

장병우(Byeung Woo Jang),유한기(Hna Ki Yu),박혜영(Hae Young Park) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.2

목적 : 조직의 노화과정에 미토콘드리아 유전자 결손이 밀접한 관련이 있는바, 폐경 여성의 난소는 시기적으로 여성의 노화가 가속화하는 시간으로 미토콘드리아 유전자 결손과 여성의 노화과정의 연관성을 보고자, 폐경을 전후한 여성 난소에서 미토콘드리아 유전자 결손이 노화에 미치는 상관관계를 알아보고자 하였다. 연구 방법 : 폐경 전 여성 35례와 폐경 후 여성 17례에서 얻어진 난소, 자궁근종, 자궁근육 조직에 대하여 결손된 미토콘드리아 유전자 부위에 대한 중합효소연쇄반응을 시행하였고, 증폭된 시료에 대한 전기영동을 실시하여 미토콘드리아 유전자 결손의 band를 확인하고, 그 염기서열을 분석하였다. 결과 : 미토콘드리아 유전자 결손은 4977 bp결손과 3805 bp결손, 7150 bp결손, 5777 bp결손이 있었고 난소조직에서 4977 bp결손은 폐경 후 여성 난소에서 62.5%, 폐경 전 여성 난소에서 20.0%로 폐경 후 여성의 난소에서 높은 빈도의 양성율을 보였으며, 통계적으로 유의한 차이를 보였다 (p<0.05). 4977 bp결손, 3805 bp결손, 7150 bp결손 및 5777 bp결손 모두 폐경 후 여성의 난소 조직에서 자궁근종 조직이나 자궁근육 조직에 비하여 높은 빈도를 보였고, 통계적으로 유의하였다 (p<0.05). 결론 : common deletion으로 알려진 4,977 bp결손의 경우 폐경 후 여성의 난소에서 통계적으로 유의한 결과를 확인할 수 있었다. 또한 3805 bp결손, 7150 bp결손과 5777 bp결손은 모두 보고되지 않은 새로운 결손위치이며, 그 중 5777 bp 결손은 한국인에서 많이 나타나는 것을 확인할 수 있었다. 추후 많은 연구의 가능성을 갖고 있다고 생각되며, 본 연구 결과 폐경 후 여성의 난소에서 높은 빈도로 보여지는 미토콘드리아 유전자 결손은 폐경과 관련하여 난소의 노화과정에 나타나는 원인인자로 생각된다. Objective : The age-associated changes of mtDNA include nucleotide deletion, point mutations, as well as modifications. Age associated alterations of mtDNA occur in several different species; however, their physiological relevance remains unclear. The function of human ovary changes dramatically around the menopausal period. However, the mechanism of menopause and ovarian aging is not well understood. Thus, to study the regulatory mechanism of ovarian dysfunction by aging, the accumulation of mtDNA deletions in human ovaries from pre-menopausal and menopausal women was analyzed and compared with mtDNA deletions in myoma and myometriums of the same subjects. Method : Total DNA was extracted from these tissues, an part of mtDNA were amplified by polymerase chain reaction. The detailed locations of each of the deleted mtDNA regions were identified by sequencing. Result : Four types of mtDNA deletions were identified: a 4977 bp deletion, a 3805 bp deletion, a 7150 bp deletion, and a 5777 bp deletion. In ovaries, the occurrence of a 4977 bp deletion of mtDNA in menopausal women was significantly higher than that in pre-menopausal women, i.e., 62.5% of that in menopausal women and 20.0% of that in pre-menopausal women. In menopausal women, the occurrence of all of those four mtDNA deletions identified in this study in ovaries was higher than that in myomas and myometriums. Conclusion : A 4977 bp deletion of mtDNA between the ATPase 8 and ND5 genes in ovaries can be related to ovarian aging, especially during menopause. A 4977 bp deletion in ovaries of menopausal women can be a usuful marker of natural ovarian aging and may have a relationship to dysfunction of the ovarian aging. Three other mtDNA deletions identified in this study, a 3809 bp deletion, 7150 bp deletion, and 5777 bp deletion, was newly reported. A 5777bp deletion was found in a large amount in Korean women and further studies about this racial specificity will be needed.

임신 중반기의 무통성 자궁경관 개대에 대한 응급 자궁경관 봉축술의 임상적 의의에 대한 연구

신진웅(Jin Woong Shin),이종승(Jong Seung Lee),문희봉(Hee Bong Moon),안상권(Sang Kwon Ahn),변태섭(Tae Sup Byeun),장병우(Byeung Woo Jang),노덕영(Duck Yeong Ro),김도강(Do Kang Kim),김수평(Soo Pyung Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

N/A A retrospective study was conducted to evaluate the clinical outcomes of midtrimester emergency cervical cerclage in patients with painless cervical dilatation with/without prolapsed amniotic sac, including cases of no previous history of cervical incompetence. 10 patients including 1 twin pregnancy were teviewed for study, All had received emergency cervical cerclage with Macdonald operation or Shirodka operation at 18 to 31 weeksgestation. The procedures were carried out without serious complication except for one patient who had received re-operation 3 days after Macdonald operation because of re-protrusion of amniotic sae. The mean procedure to delivery internal was 8.9+5.3 (range 1 to 17) weeks. The mean gestational age at delivery was 32.4+5.6 (range 22 to 39+6) weeks for the entire group, 36.1+2.6 (range 32+4 to 39+6) weeks for the 6 who achived viability, and 27.6+5.0 (range 22 to 29+4) weeks for the 3 who died during the neonatal period. 1 died during gestation and was delivered at 33+6 weeksgestation. The mean birthweight was 2181.6+971.6 (range 498 to 3500)g for the entire group, and 2712.9+ 571.5 (range 1860 to 3500)g for the 7 infants who lived until after neonatal period. The total survival rate for 11 babies was 64%. This study demonstrates that midtrimester emergency cervical cerclage for the patients who have dilated cervix with/without prolapsed amniotic sac is valuable method to try in the cases predicted they would lost the baby with conservative treatment only.

정상 임신과 비정상 임신의 초기 혈중 CA - 125 수치에 관한 연구

노덕영(Duck Yeong Ro),김도강(Do Kang Kim),김수평(Soo Pyung Kim),문희봉(Hee Bong Moon),강규섭(Gyu Sub Kang),황지영(Jee Young Hwang),신봉영(Bong Young Shin),장병우(Byeung Woo Jang) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

N/A A prospective study was initiated to compare maternal serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies. Serum specimens were obtained from 87 women with a normal intrauterine pregnancy and 47 women with abnormal pregnancies which were ended in spontaneo abortion or pathologically confirmed to be missed abortion. In normal pregnancies, the mean serum CA-125 concentrations were increased significantly from amenorhea 6 weeks (139.838.7 IU/ml), and were higher statistically than the values tested in the same weeks of abnormal pregnancies. In abnormal pregnancies serum CA-125 concentations were relatively lower than those of normal pregnancies. But these differences were not statistically significant except the values tested in amenorhea 6weeks. So serum levels of CA-125 may not be proved useful in monitoring of early pregnancies outcome.

폐경 여성에서 프로제스테론 용량에 따른 지질 및 지단백 대사에 미치는 영향과 골 밀도 변화에 대한 연구

김종일,장병우,전선희,지일운,유한기 대한폐경학회 1996 대한폐경학회지 Vol.2 No.2

Menopause constitutes a sizable population of the adult wornans life, and it is resonable to con that most women will benefit from hannone replacement therapy. Also, it is important to realized that cardiovascular disease and bone fracture are a major cause of marbidity and death in the menopausal patient To study the effects of different types of progesterone on lipoprotein metabolism and bone metabolism, we treated two groups of postmenopausal women with far three weeks with conjugated equine estrogen 0.625mg per day and different sequential estrogen-pragesterone regimens as followes: Group I received medroxypmgesterone acetate, 2.5mg per day, from day 14 to day 25 of the cycle. Group II, medroxyprogesterone acetate, 5mg per day. The data demonstrated a beneficial effect in lipoprotein profiles, that total cholesterol decreased in two groups by 8.6 to 11.7 percent from the base line values. Low density lipoprotein cholesterol decrease in two groups by 18.5(group I) and 32.7 (group II) percent in post HRT 12 months. High density lipoprotein cholestaol increase during trcatment by smaller in 5.3 percent and higher in 27 percent in both groups. Triglyceride increase during initial 6 months period (6.5-28.3 percent) and decrease during post 12 months period in both groups. Lumbar BMD and Femur BMD were decrease during 6 months period and increase during later 6 months in Group I, but in Group II results shows reciprical change compared with Group I. Our result suggest that. medroxyprogesterone acetate,especially 5mg per day have the beneficial effect of postmenopausal estrogen treatment on HDL-cholesterol and so, the favorable lipoprotein profile offer protection to the cardiovascular system and medro- xyprogesterone acetate was no adverse effect to bone mineral density in postmenopausal HRT women