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Microchimerism of Fetal Origin in Ovarian Tissues from Women with Pelvic Endometriosis

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์„œ

๋ก 

์€ ์ตœ๊ทผ ๊ณผํ•™ ๊ธฐ์ˆ ์˜ ๋ฐœ์ „์— ์˜ํ•ด ์ƒˆ Microchimerism ๋กญ๊ฒŒ ๋ฐํ˜€์ง„ ํ˜„์ƒ์— ๋Œ€ํ•œ ์‹ ์กฐ์–ด์ด๋‹ค ์ฆ‰ ํ•œ ๊ฐœ์ธ์—๊ฒŒ. , ์„œ ๋‹ค๋ฅธ ๊ฐœ์ธ์—๊ฒŒ๋กœ ์ด์ „๋œ ์„ธํฌ๊ฐ€ ๋‚ฎ์€ ๋†๋„๋กœ ์กด์žฌํ•˜ ๋Š” ํ˜„์ƒ์„ ์ด์นญํ•˜๋Š” ์˜๋ฏธ์˜ ๋‹จ์–ด๋กœ์„œ, 1977๋…„Liรฉgeois ๋“ฑ์ด ์‹คํ—˜์‹ค ์ฅ์—์„œ ๋™์ข… ๊ณจ์ˆ˜ ์„ธํฌ๊ฐ€ ์•ˆ์ •๋œ ์ƒํƒœ๋กœ ๋‚ฎ ์€ ๋†๋„์˜ ์ฆ์‹์„ ๋ณด๊ณ ํ•˜๋ฉฐ ์ฒ˜์Œ ์‚ฌ์šฉ๋œ ์šฉ์–ด์ด๋‹ค.1์ด ๋Ÿฐ ์„ธํฌ๋“ค์˜ ์™•๋ž˜ (trafficking)๋Š” ์ž„์‹  ์ˆ˜ํ˜ˆ ์žฅ๊ธฐ ์ด, , ์‹๊ณผ ๊ฐ™์€ ์—ฌ๋Ÿฌ ๊ฐ€์ง€ ์ƒํ™ฉ์— ์˜ํ•ด ๋ฐœ์ƒํ•  ์ˆ˜ ์žˆ๋‹ค ํŠนํžˆ. ์ž„์‹  ์ค‘์— ํƒœ์•„์˜ ์„ธํฌ๊ฐ€ ์‚ฐ๋ชจ์˜ ํ˜ˆ์•ก ์ˆœํ™˜ ์†์œผ๋กœ ๋“ค์–ด ๊ฐ€๋Š” ๊ฒƒ์€ ์ž„์‹ ์„ ํ•œ ๋ชจ๋“  ์—ฌ์„ฑ์—๊ฒŒ์„œ ๋ณด์ด๋Š” ํ˜„์ƒ์ด ๋‹ค.2์œ ์ž…๋œ ํƒœ์•„์„ธํฌ๋Š” ๋ถ„๋งŒ๊ณผ ๋”๋ถˆ์–ด ๊ธ‰๊ฒฉํžˆ ์‚ฌ๋ผ์ง€๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์™”์œผ๋‚˜ ์•„์ฃผ ์šฐ์—ฐํ•œ ๊ธฐํšŒ์— ๋ถ„๋งŒ ํ›„ ์ˆ˜, ์‹ญ ๋…„์ด ์ง€๋‚œ ์‚ฐ๋ชจ์˜ ํ˜ˆ์•ก๊ณผ ์กฐ์ง ๋‚ด์—์„œCD34(+)์„ธํฌ ์ ‘์ˆ˜์ผ 2004. 11. 29.๏ผš ์ฃผ๊ด€์ฑ…์ž„์ž:์ฐจ๋™ํ˜„ E-mail: chadh001@hanmail.net

์ž๊ถ๋‚ด๋ง‰์ฆ ์—ฌ์„ฑ ๋‚œ์†Œ ์กฐ์ง์˜ ํƒœ์•„ ๊ธฐ์›

์— ๊ด€ํ•œ ์—ฐ๊ตฌ

microchimerism

ํฌ์ฒœ์ค‘๋ฌธ ์˜๊ณผ๋Œ€ํ•™ ์‚ฐ๋ถ€์ธ๊ณผํ•™๊ต์‹ค, *์—ฐ์„ธ๋Œ€ํ•™๊ต ์˜๊ณผ๋Œ€ํ•™ ์‚ฐ๋ถ€์ธ๊ณผํ•™๊ต์‹ค ์žฅ์ง„๋ฒ” ์ด์ˆ™ํ™˜ ์ด๋ณ‘์„โ€ค โ€ค * ๊น€์ข…์šฑ ๋ฐ•์ƒ์› ์ด์ •๋…ธ ๋ฌธ์˜๊ธฐ ์œคํƒœ๊ธฐ ์ฐจ๋™ํ˜„โ€ค โ€ค โ€ค โ€ค โ€ค โ€ค

Microchimerism of Fetal Origin in Ovarian Tissues from Women

with Pelvic Endometriosis

Jin Beum Jang, M.D., Sook Hwan Lee, M.D., Byoung Seok Lee, M.D.*, Jong Wook Kim, M.D., Sang Won Park, M.D., Chung No Lee, M.D.,

Young Ki Moon, M.D., Tae Ki Yoon, M.D., Dong Hyun Cha, M.D.

Department of Obstetrics and Gynecology, College of Medicine, Pochon CHA University, Seoul, Korea,

*Department of Obstetrics and Gynecology, College of Medicine, Yonsei University, Seoul, Korea

Objective: To investigate whether fetal microchimeric cells were detected in ovarian tissues with pelvic endometriosis.

Methods: Ovarian tissues with endometriosis were obtained from five women who had at least one live-born son and who underwent

enucleation of endometriotic cyst or oophorectomy after a diagnosis of endometriotic cyst. Control tissues were obtained from five women with endometriosis who had no pregnant history. Tissue sections were analyzed with fluorescence in situ hybridization for the presence of fetal cells, defined by X and Y chromosome.

Results: Fluorescence in situ hybridization using paraffin-embedded ovarian specimens was performed successfully. Male cells were found

in ovarian tissues from all five patients. No male cells were found in ovarian tissues from all five controls.

Conclusion: Fetal microchimeric cells, possibly from feto-maternal cell trafficking were detected in ovarian tissues with endometriosis were

obtained from women who had prior male pregnancies. Further study is necessary to understand the role of persistent fetal microchimeric cells in the progression of endometriosis.

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๊ฐ€ ๋ฐœ๊ฒฌ๋˜๋ฉด์„œ, microchimerism์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ์‹œ์ž‘ ๋˜์—ˆ๋‹ค.3 ์‹ค์ œ๋กœ ์ž„์‹ , 6์ฃผ ๊ฒฝ๋ถ€ํ„ฐ ์‚ฐ๋ชจ์˜ ํ˜ˆ์•ก์—์„œ ํƒœ์•„Y์—ผ์ƒ‰์ฒด ๋ฐฐ์—ด(sequence)์ด ๋ฐœ๊ฒฌ๋˜๋ฉฐ,4๋งค์šฐ ๋‹ค ์–‘ํ•œ ์ข…๋ฅ˜์˜ ํƒœ์•„ ์„ธํฌ ์ฆ‰ ์˜์–‘์„ธํฌ, (trophoblast), ์„ธํฌ ์„ธํฌ ์กฐํ˜ˆ ์ „๊ตฌ์„ธํฌ CD34+ , CD34+CD38+ , ๊ฐ„์—ฝ๋ชจ์„ธํฌ (hematopoietic progenitor cell),

์œ ํ•ต ์ ํ˜ˆ๊ตฌ

(mesenchymal stem cell), (neclated ์™€ ๋ฆผํ”„๊ตฌ ๋‹จํ•ต๋ฐฑํ˜ˆ๊ตฌ ์ฒœ์—ฐ ํ‚ฌ๋Ÿฌ erythroblast), T B , ,

์„ธํฌ (natural killer cell) ๋“ฑ์ด ์‚ฐ๋ชจ์˜ ํ˜ˆ์•ก์—์„œ ๋ฐœ๊ฒฌ ๋˜์—ˆ๋‹ค.5 ์ดˆ๊ธฐ์˜ ์—ฐ๊ตฌ๋Š” ๋Œ€๋ถ€๋ถ„์€ ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜ (autoimmune ์„ ๊ฐ€์ง„ ์—ฌ์„ฑ์—๊ฒŒ์„œ ์ด๋ฃจ์–ด์กŒ๋Š” disease) ๋ฐ ๊ทธ ์ด์œ ๋Š”, ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜์ด ์—ฌ์„ฑ์—๊ฒŒ ๋งŽ์ด ๋ฐœ์ƒํ•˜๋ฉฐ ํŠนํžˆ ์ž„์‹ ์„, ๊ฒฝํ—˜ํ•œ ์—ฌ์„ฑ์—์„œ ๊ธ‰๊ฒฉํžˆ ์ฆ๊ฐ€ํ•˜๊ณ  ์ผ๋ถ€ ์ž๊ฐ€๋ฉด์—ญ์งˆํ™˜, ๊ณผchronic graft versus host disease (GVHD)๊ฐ€ ์ž„ ์ƒ์ ์ธ ์œ ์‚ฌ์„ฑ์„ ๋ณด์—ฌ microchimerism์ด ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜์˜ ๋ฐœ๋ณ‘๊ณผ ๊ด€๋ จ๋œ ๊ฒƒ์œผ๋กœ ์ƒ๊ฐํ•˜์˜€๊ณ , Nelson ๋“ฑ ์€ ์ด๊ฒƒ์„ ์ฆ๋ช…ํ•˜๊ธฐ ์œ„ํ•ด ๋งŽ์€ ์—ฐ๊ตฌ๋ฅผ ํ•˜์˜€๋‹ค ์‹ค์ œ. ๋กœ ์ „์‹ ์„ฑ ๊ฒฝํ”ผ์ฆ, (systemic sclerosis)์„ ๋น„๋กฏํ•œ ๋งŽ ์€ ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜๋“ค์—์„œ ๋Œ€์กฐ๊ตฐ๋ณด๋‹ค ๋งŽ์€ ์ˆ˜์˜ ํƒœ์•„ ์„ธํฌ๋“ค์ด ๋ฐœ๊ฒฌ๋˜์—ˆ๋‹ค michrochimeric .6-8 ํ•˜์ง€๋งŒ ์ž„์‹ ์„ ๊ฒฝํ—˜ํ•œ ์—ฌ์„ฑ์—๊ฒŒ์„œ ๋ฐœ์ƒํ•œ ํ˜• ๊ฐ„์—ผ, C 9 ์ด๋‚˜ ์ž๊ถ ๊ฒฝ๋ถ€์•”10๊ณผ ๊ฐ™์€ ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜ ์ด์™ธ์˜ ์งˆ๋ณ‘ ์—์„œ๋„ ๋ณ‘๋ณ€์ด๋‚˜ ์ฃผ์œ„ ์กฐ์ง์— ํƒœ์•„ ์„ธํฌ๋“ค์ด ๊ด€์ฐฐ๋˜๋ฉด ์„œ ํƒœ์•„ ์„ธํฌ์˜, microchimerism์ด๋ผ๋Š” ํ˜„์ƒ์ด ์™œ ์—ฌ ์„ฑ์—๊ฒŒ์„œ ๋‚˜ํƒ€๋‚˜๋ฉฐ ์ด๋Ÿฌํ•œ ํ˜„์ƒ๊ณผ ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•๊ณผ๋Š” ์–ด ๋– ํ•œ ์ƒ๊ด€๊ด€๊ณ„๊ฐ€ ์žˆ๋Š” ๊ฒƒ์ธ๊ฐ€์— ๋Œ€ํ•ด ์˜๋ฌธ์ด ์ฆ๊ฐ€ํ•˜๊ณ  ์žˆ์œผ๋ฉฐ ์ด์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ๋งค์šฐ ํฅ๋ฏธ๋กญ๊ฒŒ ์ง„ํ–‰๋˜๊ณ  ์žˆ๋‹ค. ์ž๊ถ๋‚ด๋ง‰์ฆ์€ ์ „ํ†ต์ ์œผ๋กœ ์ž๊ถ๋‚ด๊ฐ• ์ด์™ธ์˜ ๊ณณ์— ์ž๊ถ ๋‚ด๋ง‰ ์กฐ์ง์ด ์กด์žฌํ•˜๋Š” ์งˆํ™˜์œผ๋กœ ์ •์˜ํ•  ์ˆ˜ ์žˆ๋‹ค ์ž๊ถ๋‚ด. ๋ง‰์ฆ์€ ์–‘์„ฑ์˜ ๋งŒ์„ฑ์ ์ธ ์—ผ์ฆ์„ฑ ์งˆํ™˜์ด๋ฉฐ ํŠน์ง•์ ์ธ ์ž„, ์ƒ ์–‘์ƒ์œผ๋กœ๋Š” ๋งŒ์„ฑ ๊ณจ๋ฐ˜ํ†ต ์›”๊ฒฝํ†ต ์„ฑ๊ตํ†ต๊ณผ ๊ฐ™์€ ํ†ต, , ์ฆ๊ณผ ๋ถˆ์ž„ ๋“ฑ์„ ๋ณด์ธ๋‹ค ๊ฐ€์žฅ ํ”ํ•œ ํ˜•ํƒœ์ธ ๊ณจ๋ฐ˜๋‚ด ์ž๊ถ. ๋‚ด๋ง‰์ฆ์€ ๊ฐ€์ž„๊ธฐ ์—ฌ์„ฑ์˜15-20% ์ •๋„์—์„œ ๋ฐœ๋ณ‘ํ•˜๋ฉฐ, ๋ถˆ์ž„ ํ™˜์ž์˜ ๊ฒฝ์šฐ์—๋Š”30-50%์ •๋„์—์„œ ๋ฐœ์ƒํ•  ์ •๋„๋กœ ํ”ํ•œ ๋ถ€์ธ๊ณผ ์งˆํ™˜์ด๋‹ค.11 ๊ณจ๋ฐ˜๋‚ด ์ž๊ถ๋‚ด๋ง‰์ฆ์˜ ๋ฐœ์ƒ ๊ธฐ์ „์œผ๋กœ๋Š” ํฌ๊ฒŒ ์ฐฉ์ƒ์ด

๋ก  (implantation theory)๊ณผ ํ™”์ƒ์ด๋ก  (metaplasia ์ด ์ œ๊ธฐ๋˜๊ณ  ์žˆ๋‹ค ์ฐฉ์ƒ์ด๋ก ์€ ์ตœ์ดˆ ์›์ธ theory) . ์œผ๋กœ ๋‚œ๊ด€์„ ํ†ตํ•˜์—ฌ ์ •์ƒ ์œ„์น˜์˜ ์ž๊ถ (primum moven) ๋‚ด๋ง‰ ์„ธํฌ๋“ค์ด ๋ณต๊ฐ•๋‚ด๋กœ ์—ญ๋ฅ˜ํ•ด์„œ ๋ณต๋ฒฝ์— ์œ ์ฐฉ๋˜๊ณ  ์ฆ ์‹ํ•˜์—ฌ ์ž๊ถ๋‚ด๋ง‰์ฆ ๋ณ‘๋ณ€์„ ํ˜•์„ฑํ•œ๋‹ค๋Š” ์ด๋ก ์ด๋‹ค ๋ชจ๋“ . ์—ฌ์„ฑ์˜ ์•ฝ80%์—์„œ ์ƒ๋ฆฌ์˜ ์—ญ๋ฅ˜๊ฐ€ ๋ฐœ์ƒํ•˜๋ฏ€๋กœ ์ž๊ถ๋‚ด, ๋ง‰์ฆ์€ ๋‹ค๋ฅธ ์š”์ธ๋“ค์ด ํ•จ๊ป˜ ์ž‘์šฉ์„ ํ•˜์—ฌ ๋ฐœ์ƒํ•œ๋‹ค ์ž๊ถ. ๋‚ด๋ง‰ ์„ธํฌ์˜ ์ฆ์‹๊ณผ ์ฐฉ์ƒ์„ ํ—ˆ์šฉํ•˜๋Š” ์š”์†Œ (permissive ๊ฐ€ ์žˆ์œผ๋ฉฐ ์ด๋Ÿฐ ์š”์†Œ๋“ค๋กœ ์ธํ•˜์—ฌ ๋ณต๊ฐ•๋‚ด ์ฒด์•ก factor) , ์˜ ์ƒํ™”ํ•™์  ์„ธํฌํ•™์  ๊ตฌ์„ฑ ์„ฑ๋ถ„์ด (peritoneal fluid) , ๋‚˜ ๋ฉด์—ญ๋ฐ˜์‘ ๋“ฑ์˜ ๋ณ€ํ™”๊ฐ€ ์˜ค๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค ์ด. ์— ๋ฐ˜ํ•ด ํ™”์ƒ์ด๋ก ์€ ๋ณต๊ฐ•๋‚ด, mรผllerian ํ˜•์˜ ๋‚ด๋ง‰ ์„ธํฌ ๊ฐ€ ์„ฑํ˜ธ๋ฅด๋ชฌ์— ์˜์กดํ•˜์—ฌ ๋ณ€ํ˜• (transformation)๋œ๋‹ค๋Š” ๊ฐ€์„ค๋กœ ๋‚จ์„ฑ์—์„œ์˜ ์ž๊ถ๋‚ด๋ง‰์ฆ์ด๋‚˜ ์ƒ๋ฆฌ๊ฐ€ ์—†๋Š” ์—ฌ์„ฑ์˜ ์ž๊ถ๋‚ด๋ง‰์ฆ์„ ์„ค๋ช…ํ•˜๋Š” ์ด๋ก ์ด ๋˜๊ณ  ์žˆ๋‹ค ๋‘ ๊ฐ€์ง€ ์ด๋ก . ์€ ์„œ๋กœ ์ƒ๋ณด์ ์ด๊ธด ํ•˜์ง€๋งŒ ๋Œ€๋ถ€๋ถ„์˜ ์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋Š” ์ฐฉ์ƒ, ์ด๋ก ์„ ์ง€์ง€ํ•˜๋Š” ๊ฒฐ๊ณผ๋“ค์„ ๋ณด๊ณ ํ•˜๊ณ  ์žˆ๋‹ค.12 ๊ทธ๋Ÿฌ๋‚˜, Gleicher ๋“ฑ์ด ์ž๊ถ๋‚ด๋ง‰์ฆ ํ™˜์ž์˜ 40-60% ์ •๋„์—์„œ ์ž๊ฐ€ํ•ญ์ฒด๊ฐ€ ์ฆ๊ฐ€ํ•œ ๊ฒƒ์„ ๋ณด๊ณ ํ•˜๋ฉฐ,13์ž๊ถ๋‚ด๋ง‰ ์ฆ์˜ ๋ฐœ์ƒ ๊ธฐ์ „์„ ์ž๊ฐ€๋ฉด์—ญ์งˆํ™˜์œผ๋กœ ์„ค๋ช…ํ•˜๋ ค๋Š” ๊ฐ€์„ค์„ ์ œ์‹œํ•œ ์ดํ›„๋กœ ๋‹ค๋ฅธ ์ž๊ฐ€๋ฉด์—ญ์งˆํ™˜๊ณผ ๋™๋ฐ˜ํ•˜๋Š” ๊ฒฝ์šฐ๊ฐ€, ๋งŽ๊ณ  ์Šต๊ด€์„ฑ ๋ฉด์—ญ ๋งค๊ฐœ ์œ ์‚ฐ๊ณผ์˜ ๊ด€๋ จ์„ฑ ๋•Œ๋ฌธ์— ์ตœ๊ทผ ๋“ค ์–ด ์ž๊ถ๋‚ด๋ง‰์ฆ์„ ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜์œผ๋กœ ์ ‘๊ทผํ•˜๋Š” ์‹œ๋„๊ฐ€ ๋Š˜๊ณ  ์žˆ๋‹ค.14 ๋ณธ ์—ฐ๊ตฌ์—์„œ ์ €์ž๋“ค์€ ์ฒซ์งธ ํƒœ์•„์„ธํฌ์˜, microchi-์ด ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜์„ ํฌํ•จํ•˜๋Š” ์—ฌ๋Ÿฌ ์งˆํ™˜๊ณผ ๊ด€๋ จ merism ์„ฑ์ด ์žˆ์œผ๋ฉฐ ๋‘˜์งธ ์ž๊ถ๋‚ด๋ง‰์ฆ์ด ๋ถ€์ธ๊ณผ์ ์œผ๋กœ ํ”ํ•œ, , ์งˆํ™˜์ด๊ณ  ๋˜ํ•œ ์ž๊ฐ€๋ฉด์—ญ์งˆํ™˜์˜ ํŠน์ง•์„ ๊ฐ€์ง€๊ณ  ์žˆ์œผ๋ฏ€๋กœ ํƒœ์•„์„ธํฌ์˜ microchimerism์ด ๋ถ„๋งŒ์„ ๊ฒฝํ—˜ํ•œ ์—ฌ์„ฑ์˜ ์ž๊ถ๋‚ด๋ง‰์ฆ ์กฐ์ง์—์„œ ๋ฐœ๊ฒฌ๋œ๋‹ค๋Š” ๊ฐ€์„ค์„ ์„ธ์šฐ๊ฒŒ ๋˜์—ˆ ๋‹ค ์ด๋ฅผ ์œ„ํ•ด ์ž๊ถ๋‚ด๋ง‰์ฆ ์กฐ์ง์—์„œ ํ˜•๊ด‘ ์ œ์ž๋ฆฌ๋ณดํ•ฉ๊ฒฐ. ํ•ฉ๋ฒ• (fluorescence in situ hybridization, ์ดํ•˜ FISH ๋กœ ์•ฝํ•จ ์„ ์ด์šฉํ•˜์—ฌ ํƒœ์•„์„ธํฌ์˜) microchimerism์„ ํ™• ์ธํ•˜์˜€๋‹ค.

(3)

์—ฐ๊ตฌ ๋Œ€์ƒ 1. ์—ฐ๊ตฌ ๋Œ€์ƒ์€ ๋‚œ์†Œ์˜ ์ž๊ถ๋‚ด๋ง‰์ฆ์œผ๋กœ ์‚ฐ๋ถ€์ธ๊ณผ์—์„œ ์ง„๋‹จ๋œ 10๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€๋‹ค ์—ฐ๊ตฌ๊ตฐ์œผ๋กœ ์ ์–ด๋„. ํ•œ ๋ช… ์ด์ƒ์˜ ๋‚จ์•„๋ฅผ ์ถœ์‚ฐํ•œ ๊ฒฝํ—˜์ด ์žˆ๋Š” ์—ฌ์„ฑ์—์„œ ์ž ๊ถ๋‚ด๋ง‰์ฆ์ด ์ง„๋‹จ๋œ ํ›„ ์ž๊ถ๋‚ด๋ง‰์ข…์ ˆ์ œ์ˆ  ํ˜น์€ ๋‚œ์†Œ์ ˆ ์ œ์ˆ ์„ ์‹œํ–‰ํ•œ ํ™˜์ž ๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€๊ณ  ๋Œ€์กฐ๊ตฐ์œผ5 , ๋กœ๋Š” ์ž„์‹ ์˜ ๊ฒฝ๋ ฅ์ด ์—†๋Š” ์—ฌ์„ฑ์—์„œ ์ž๊ถ๋‚ด๋ง‰์ฆ์„ ์ง„๋‹จ ํ•˜๊ณ  ์ž๊ถ๋‚ด๋ง‰์ข…์ ˆ์ œ์ˆ  ํ˜น์€ ๋‚œ์†Œ์ ˆ์ œ์ˆ ์„ ์‹œํ–‰ํ•œ ํ™˜ ์ž ๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€๋‹ค5 . Table 1์€ ํ™˜์ž๊ตฐ๊ณผ ๋Œ€์กฐ ๊ตฐ์˜ ์‚ฐ๊ณผ๋ ฅ์— ๋Œ€ํ•ด ๋น„๊ตํ•œ ๊ฒƒ์ด๋‹ค ๋‘ ๊ตฐ ๋ชจ๋‘์—์„œ. ์„ ๋งŒ๋“ค ๊ฐ€๋Šฅ์„ฑ์ด ์žˆ๋Š” ๋‹ค๋ฅธ ์ƒํ™ฉ ์ฆ‰ microchimerism , ์ˆ˜ํ˜ˆ ์žฅ๊ธฐ ์ด์‹ ๋“ฑ์€ ์—†์—ˆ๋‹ค, . ๋ฐฉ๋ฒ• 2. ๋Š” ์™€ ์—ผ์ƒ‰์ฒด ์†Œ์‹์ž๋ฅผ ์ด์šฉํ•˜์—ฌ ์ด์ „์˜ ๊ธฐ FISH X Y ์ˆ ๋œ ๋ฐฉ๋ฒ•์— ๋”ฐ๋ผ ๋‹ค์Œ๊ณผ ๊ฐ™์ด ์‹œํ–‰ํ•˜์˜€๋‹ค.155 ยตM๋‘๊ป˜ ํŒŒ๋ผํ•€ ๊ณ ์ •๋œ ์กฐ์ง ์ ˆํŽธ์„ ์–‘์ „ํ•˜๊ฐ€ ์ถฉ์ „๋œ ์Šฌ๋ผ์ด๋“œ ๋กœ ๋งŒ๋“ค์–ด37โ„ƒ์—์„œ overnightํ•œ๋‹ค ํŒŒ๋ผํ•€ ์ œ๊ฑฐ๋ฅผ ์œ„. ํ•ด 100% xylene ์šฉ์•ก์— 10๋ถ„๊ฐ„ ๋ฒˆ ์”ป๋Š”๋‹ค3 . 100%, ์—ํƒ„์˜ฌ๋กœ ๊ฐ๊ฐ ๋ถ„์”ฉ ์„ ํ•œ ํ›„ 85%, 70% 5 rehydration , ์—ผ์‚ฐ ์šฉ์•ก์— ๋ถ„๊ฐ„ ์ฒ˜๋ฆฌํ•œ๋‹ค ์—์„œ 0.2 M 20 . 80โ„ƒ 2x

SCC (0.3 M sodium chloride and 0.03 M sodium

์šฉ์•ก์œผ๋กœ ๋ถ„๊ฐ„ ์ฒ˜๋ฆฌํ•œ๋‹ค ๋ฅผ ์‚ฌ

citrate) 20 . TEN buffer ์šฉํ•œ 0.05 mg/mL proteinase K ์šฉ์•ก์œผ๋กœ 37โ„ƒ์—์„œ

๋ถ„๊ฐ„ ์ฒ˜๋ฆฌํ•œ๋‹ค ์šฉ์•ก์œผ๋กœ ๋ถ„๊ฐ„

10 . 4% formaldehyde 10 ๊ณ ์ •์‹œํ‚จ๋‹ค. 70%, 85%, 100%์—ํƒ„์˜ฌ๋กœ ํƒˆ์ˆ˜์‹œํ‚จ ํ›„

Table 1. Reproductive History of Patients with Endometriosis

Study group

Pregnancy history

Control group

Pregnancy history

Male Female Abortion Male Female Abortion

Case 1 1 0 2 Case 6 0 0 0 Case 2 2 0 1 Case 7 0 0 0 Case 3 1 1 1 Case 8 0 0 0 Case 4 1 1 0 Case 9 0 0 0 Case 5 2 0 1 Case 10 0 0 0 ๊ณต๊ธฐ ์ค‘์— ๋ง๋ฆฐ๋‹ค ์ƒ์šฉํ™”๋˜์–ด ์‚ฌ์šฉ์ด ๊ฐ€๋Šฅํ•œ. Vysis ํšŒ์‚ฌ์˜ ์—ผ์ƒ‰์ฒด ์†Œ์‹์ž (Downers Grove, IL, USA) X

๋Š” ์ ์ƒ‰ ํ˜•๊ด‘์„ ๋ณด์ด๋Š” ๋กœ ํ•˜

(DXZ1) cyanine-3 labeling ๊ณ , Y ์—ผ์ƒ‰์ฒด ์†Œ์‹์ž(PHY10)๋Š” ๋…น์ƒ‰ ํ˜•๊ด‘์„ ๋ณด์ด๋Š”

๋กœ ์„ ํ•˜์—ฌ

isothiocyanate labeling 16 ๋งŒ๋“  FISH ์†Œ์‹์ž ์„ ์ ˆํŽธ์— ์ฒจ๊ฐ€ํ•œ๋‹ค ์†Œ์‹์ž์™€ ๋ชฉํ‘œ ๋ณ€ cocktail . DNA ์„ฑ (denaturation)์„ ์œ„ํ•ด90โ„ƒ ์˜ค๋ธ์—์„œ 10๋ถ„๊ฐ„ ์ฒ˜ ๋ฆฌํ•œ๋‹ค ๋‹ค์Œ๋‚ . formamide๋กœ ๊ณ ์ • ํ›„ 2x SCC/0.03 ๋กœ ยตg/mL DAPI (4.6-diamidino-2-phenylindole) ํ•œ๋‹ค counterstain . ๋Œ€์ƒ ํ™˜์ž๊ตฐ๊ณผ ๋Œ€์กฐ๊ตฐ์˜ ์ถœ์‚ฐ๋ ฅ์— ๋Œ€ํ•ด ๋ชจ๋ฅด๋Š” ํŒ๋… ์ž์— ์˜ํ•˜์—ฌscoring์ด ์‹œํ–‰๋˜์—ˆ๋‹ค ๋‹ค์Œ ์„ธ ๊ฐ€์ง€ ๊ธฐ์ค€. ์„ ๋งŒ์กฑ์‹œํ‚ค๋Š” ์กฐ์ง ํ‘œ๋ณธ์„ ๋ถ„์„์— ํฌํ•จ ์‹œ์ผฐ๋‹ค ์ฒซ์งธ. , ์กฐ์ง ์ ˆํŽธ์„ ๋ณดํ•ฉ๊ฒฐํ•ฉ๋ฒ• ์‹œํ–‰ํ•˜๋Š” ๋™์•ˆ์˜ ์„ธํฌ ์†์‹ค์ด ์ตœ์†Œ์ธ ๊ฒฝ์šฐ ๋‘˜์งธ, , 75%์ด์ƒ์˜ ํ•ต์—์„œFISH signal์„ ๋ณด์ด๋Š” ๊ฒฝ์šฐ ์…‹์งธ, , X์™€ Y ์—ผ์ƒ‰์ฒด์˜ signal์ด ๊ฐ™์€ ๊ฐ• ๋„ (intensity)๋กœ ๋ณด์ด๋Š” ๊ฒฝ์šฐ๋ฅผ ๊ธฐ์ค€์œผ๋กœ ํ•˜์˜€๋‹ค ์ด. ๊ธฐ์ค€์ด ์ถฉ์กฑ๋˜๋Š” ๊ฒฝ์šฐ ๊ฐ ํ™˜์ž ๋‹น ๊ฐœ์˜ ์Šฌ๋ผ์ด๋“œ๋ฅผ ๋ถ„3 ์„ํ•˜๊ณ  scoring ํ•˜์˜€๋‹ค. Leica ํ˜•๊ด‘ ํ˜„๋ฏธ๊ฒฝ 400 ๋ฐฐ์œจ ๋กœ scoring์„ ํ•˜์˜€๊ณ  ๊ฐ๊ฐ์˜, Y signal ์–‘์„ฑ์œผ๋กœ ์ƒ๊ฐ ๋˜๋Š” ์„ธํฌ๋“ค์€ 1000 ๋ฐฐ์œจ์—์„œ FISH signal์˜ ์ง„์œ„๋ฅผ ๊ฐ€๋ ธ๋‹ค.

๊ฒฐ

๊ณผ

์€ ์—ฐ๊ตฌ๊ตฐ์˜ ๋‚œ์†Œ ์กฐ์ง์—์„œ ๊ด€์ฐฐ๋œ ๋‚จ์„ฑ ์„ธํฌ Fig. 1 ์˜ ์˜ˆ๋ฅผ ๋ณด์—ฌ์ฃผ๋Š” ์‚ฌ์ง„์ด๋‹ค (male cell) . ๋‚จ์•„ ์ถœ์‚ฐ๋ ฅ์ด ์žˆ๋Š” ์—ฐ๊ตฌ๊ตฐ ๋ช… ๋ชจ๋‘์—์„œ ๋‚จ์„ฑ ์„ธํฌ5

(4)

๊ฐ€ ๊ด€์ฐฐ๋˜์—ˆ๋‹ค ๊ด€์ฐฐ๋œ ๋‚จ์„ฑ ์„ธํฌ์˜ ์ˆ˜๋Š” ๊ฐ ํ™˜์ž๋“ค์˜. ๋ถ„์„ํ•œ ์ ˆํŽธ์—์„œ ๋น„๊ต์  ์ผ์ •ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค ๋˜ํ•œ ๋ช‡. , ๋ช‡ ๊ฒฝ์šฐ์—์„œ๋Š” ๋‚จ์„ฑ ์„ธํฌ๋“ค์ด ์ง‘๋‹จ(cluster)์„ ์ด๋ฃจ์–ด ์„œ ๊ด€์ฐฐ๋˜๊ธฐ๋„ ํ•˜์˜€๋‹ค(case 2์™€case 4). ์ด์™€๋Š” ๋Œ€์กฐ ์ ์œผ๋กœ ์ถœ์‚ฐ๋ ฅ์ด ์—†๋Š” ๋Œ€์กฐ๊ตฐ์˜ ๊ฒฝ์šฐ์—์„œ๋Š” ๋‚จ์„ฑ ์„ธํฌ ๊ฐ€ ๋ช… ๋ชจ๋‘์—์„œ ๊ด€์ฐฐ๋˜์ง€ ์•Š์•˜๋‹ค5 (Table 2).

Fig. 1. Photographs show FISH using Cyanine 3-labeled X (orange) and fluorescein isothiocyanate-labeled Y (green) chromosome

probes. Nuclei are counterstained with 4โ€™,6- diamidino-2-phenylindole (blue). Male microchimeric cells with 1 Y chromosome (green) and 1 X chromosome (orange) are present within ovarian tissue. A (magnification X400) B (magnification X1000).

Table 2. Numbers of Microchimeric Male Cells Observed in Ovarian Tissue by FISH

Study group

Numbers of microchimeric cell

Slide 1 Slide 2 Slide 3

Case 1 4 (cluster of 3) 4 (cluster of 3) 3 (cluster of 3)

Case 2 16 (cluster of 11,2,2) 2 2

Case 3 5 (cluster of 2) 7 (cluster of 2) 5

Case 4 9 (cluster of 7) 11 (cluster of 5,2) 16 (cluster of 6,3)

Case 5 3 7 (cluster of 4,3) 7 (cluster of 2,5)

Control group Case 6 0 0 0 Case 7 0 0 0 Case 8 0 0 0 Case 9 0 0 0 Case 10 0 0 0

๊ณ 

์ฐฐ

๋ณธ ์—ฐ๊ตฌ์—์„œ ์ƒ์กด ๋‚จ์•„๋ฅผ ๋ถ„๋งŒ ํ›„ ์ž๊ถ๋‚ด๋ง‰์ฆ์ด ๋ฐœ ์ƒํ•œ ๋‚œ์†Œ ์กฐ์ง์—์„œ ํƒœ์•„ ๊ธฐ์›์˜ michrochimerism ์„ธํฌ๊ฐ€ ๋ฐœ๊ฒฌ๋˜๋Š” ๊ฒƒ์„ ๊ด€์ฐฐํ•˜์˜€๋‹ค ํ•˜์ง€๋งŒ ์ง€๊ธˆ๊นŒ์ง€. , ๊ณ ์ •๋œ ๋‹ค์–‘ํ•œ ์กฐ์ง๋“ค ์˜ˆ๋ฅผ ๋“ค๋ฉด ํ”ผ๋ถ€ ๋น„ paraffin , , ,

A

B

(5)

์žฅ ์ž๊ถ๊ฒฝ๋ถ€ ๋Œ€์žฅ ๊ฐ„ ๋“ฑ์—์„œ, , , FISH๊ฐ€ ์„ฑ๊ณต์ ์œผ๋กœ ์ง„ ํ–‰๋˜์—ˆ์œผ๋‚˜ ํŒŒ๋ผํ•€์— ์˜ํ•ด ๊ณ ์ •๋œ ๋‚œ์†Œ ์กฐ์ง์—์„œ์˜, ๋Š” ์ตœ์ดˆ๋กœ ์‹œํ–‰๋˜์—ˆ๊ณ  ๋ฐฉ๋ฒ•์„ ์ตœ์ ํ™”์‹œํ‚ค๋Š”๋ฐ ์–ด FISH , ๋ ค์›€์ด ์žˆ์—ˆ๋‹ค ๊ธฐ๋ณธ์ ์œผ๋กœ. paraffin bloc ์ƒํƒœ์˜ ์กฐ์ง ์„ ๊ฐ€์ง€๊ณ  FISH๋ฅผ ์‹œํ–‰ํ•˜๊ณ  ์ด๊ฒƒ์„, scoring ํ•˜๊ธฐ ์œ„ ํ•ด์„œ๋Š”5 ยตM ๋‘๊ป˜๋กœ ์ž˜๋ฆฌ์–ด ์–‘์„ฑ ์ „ํ•˜๋ฅผ ๋ค ์Šฌ๋ผ์ด๋“œ ์— ๊ณ ์ •๋œ ์กฐ์ง ์ „์ฒด์˜ ์„ธํฌ๋“ค (positive charged slide)

์ด ๋งค์šฐ ์ผ์ •ํ•œFISH signal์„ ๊ฐ–๊ณ  ์žˆ์–ด์•ผ ํ•˜๋ฉฐ ์ €๋ฐฐ, ์œจ(400 )๋ฐฐ ๋กœ ์ถฉ๋ถ„ํžˆ ํŒ๋… ๊ฐ€๋Šฅํ•ด์•ผ ํ•œ๋‹ค ์™œ๋ƒํ•˜๋ฉด ์ „. , ์ฒด์ ์œผ๋กœ ์ผ์ •ํ•œsignal์„ ๊ฐ–๊ณ  ์žˆ์ง€ ์•Š์€ ๊ฒฝ์šฐ์—๋Š” ๋งค ์šฐ ํฌ๊ท€ํ•œ ๋ชฉํ‘œ์„ธํฌ(target cell, ์ฆ‰, male fetal cell) ๋ฅผ ์‹คํ—˜ ํŒ๋… ๊ณผ์ •์—์„œ ๋ˆ„๋ฝ์‹œํ‚ฌ ์ˆ˜ ์žˆ๊ธฐ ๋•Œ๋ฌธ์— ์™„์ „ํžˆ ๋‹ค๋ฅธ ๊ฒฐ๊ณผ๋ฅผ ์–ป์„ ์ˆ˜ ์žˆ๋‹ค ๋˜ํ•œ ์ €๋ฐฐ์œจ. (400 )๋ฐฐ ๋กœ ํ•˜๋‚˜ ์˜ ์Šฌ๋ผ์ด๋“œ๋ฅผ ํŒ๋…ํ•˜๋Š”๋ฐ ๋ณดํ†ต ํ•˜๋ฃจ์— ์‹œ๊ฐ„์”ฉ ์ผ์˜, 4 6 ์‹œ๊ฐ„์ด ๊ฑธ๋ฆฌ๊ธฐ ๋•Œ๋ฌธ์— ๋งŒ์ผ ๊ณ ๋ฐฐ์œจ, (1,000 )๋ฐฐ ๋กœ ํŒ๋… ๊ฐ€๋Šฅํ•œFISH๊ฒฐ๊ณผ๋ฅผ ๊ฐ–๋Š”๋‹ค๋ฉด ์Šฌ๋ผ์ด๋“œ ํ•œ ์žฅ์„ ์™„์ „ํžˆ ํŒ๋…ํ•˜๋Š”๋ฐ ์•ฝ ๋‹ฌ์˜ ์‹œ๊ฐ„์ด ์†Œ์š”๋˜๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค ๊ทธ๋Ÿฌ1 . ๋ฏ€๋กœ, FISH signal์˜ ์„ ๋ช…๋„๊ฐ€ ๋งค์šฐ ์ค‘์š”ํ•˜๋‹ค ์—ฌ๋Ÿฌ ๊ฐ€. ์ง€ ์ค‘์š”ํ•œ ๋‹จ๊ณ„๊ฐ€ ์žˆ์ง€๋งŒ ๊ฐ€์žฅ ์ค‘์š”ํ•œ ๊ณผ์ •์€, 80โ„ƒ์˜ ๊ณ ์˜จ๊ณผproteinase K์— ๋…ธ์ถœ๋˜๋Š” ์‹œ๊ฐ„์„ ์ตœ์ ํ™”ํ•˜๋Š” ๊ฒƒ ์ด์—ˆ๋‹ค ์ ์ ˆํ•œ ์‹œ๊ฐ„ ์ด์ƒ ๋…ธ์ถœ ์‹œ์—๋Š” ๊ทธ๊ฒƒ์ด ๋ช‡ ์ดˆ์ผ. ์ง€๋ผ๋„ ์กฐ์ง ๋ง๋‹จ์˜ ์†Œ์‹ค์ด ๋งŽ์•˜๊ณ  ์ ์ ˆํ•œ ์‹œ๊ฐ„๋ณด๋‹ค ์ , ๊ฒŒ ๋…ธ์ถœ๋œ ๊ฒฝ์šฐ๋Š” ํ˜•๊ด‘ ์†Œ์‹์ž๊ฐ€ ์กฐ์ง ์„ธํฌ์˜ ํ•ต์— ๊ฒฐํ•ฉ ๋˜์ง€ ์•Š์•„์„œ ์ €๋ฐฐ์œจ์—์„œ ํŒ๋…ํ•  ์ˆ˜๊ฐ€ ์—†์—ˆ๋‹ค. ์„ ์ผ์œผํ‚ค๋Š” ์ž„์‹  ์ค‘์˜ ์„ธํฌ์˜ Michrochimerism ์™•๋ž˜๋Š” ํƒœ์•„์™€ ์‚ฐ๋ชจ ์‚ฌ์ด์— ์–‘๋ฐฉํ–ฅ (bi-directional ์œผ๋กœ ์ผ์–ด๋‚˜๋ฉฐ ์‚ฐ๋ชจ์˜ ์„ธํฌ๋“ค์ด ํƒœ์•„ ์ˆœํ™˜ trafficking) , ์— ๋“ค์–ด๊ฐ€์„œ ํƒœ์•„์˜ ์กฐ์ง์œผ๋กœ ์ด๋™๋จ์„ ๋ณด๊ณ ํ•œ ๋ฐ”๊ฐ€ ์žˆ ๋‹ค.17์ด์ „์— ๋‚จ์ž ์•„๊ธฐ๋ฅผ ์ถœ์‚ฐํ•œ ๊ฒฝํ—˜์ด ์žˆ๋Š” ๊ฑด๊ฐ•ํ•œ ์‚ฐ ๋ชจ์˜30-50%๊นŒ์ง€ ํƒœ์•„ ์„ธํฌ์—์„œ ๊ธฐ์›๋œ ๋‚จ์„ฑ ์„ธํฌ๋“ค์ด ๋ฐœ๊ฒฌ๋˜์ง€๋งŒ,18 ์•„์ง๊นŒ์ง€ ์ด๋Ÿฌํ•œ ์žฅ๊ธฐ๊ฐ„์˜ ํƒœ์•„ ์„ธํฌ์˜ ์ด ์‚ฐ๋ชจ์—๊ฒŒ ์–ด๋– ํ•œ ์˜ํ–ฅ์„ ์ฃผ๋Š”์ง€์— microchimerism ๋Œ€ํ•œ ์—ฐ๊ตฌ๋Š” ์‹œ์ž‘ํ•˜๋Š” ์ˆ˜์ค€์— ๋ถˆ๊ณผํ•˜๋‹ค. ์—ฌ๋Ÿฌ ๋ณด๊ณ ์ž๋“ค์— ์˜ํ•ด์„œ ์ „์‹ ์„ฑ ๊ฒฝํ”ผ์ฆ (systemic sclerosis),6-8 ์†Œ์•„๊ธฐ ํŠน๋ฐœ์„ฑ ์—ผ์ฆ์„ฑ ๊ทผ๋ณ‘ (juvenile idiopathic inflammatory myopathy),19 Graves ๋ณ‘ (Graves's disease),20ํ•˜์‹œ๋ชจํ†  ๊ฐ‘์ƒ์„ ์ข… (Hashimoto's

thyroditis),21 Sjรถgren ์ฆํ›„๊ตฐ(Sjรถgren's syndrome),22 ์›๋ฐœ์„ฑ ๋‹ด๋„์„ฑ ๊ฐ„๊ฒฝ๋ณ€์ฆ (primary biliary cirrhosis),23 ์ „์‹ ์„ฑ ํ™๋ฐ˜์„ฑ ๋‚ญ์ฐฝ (systemic lupus erythematosus)24 ๋“ฑ์˜ ์ž๊ฐ€ ๋ฉด์—ญ์งˆํ™˜(autoimmune disease)์˜ ๋ฐœ์ƒ์— ์ด ์ผ์ •ํ•œ ์—ญํ• ์„ ํ•  ์ˆ˜ ์žˆ๋Š” ๊ฐ€๋Šฅ์„ฑ microchimerism

์— ๋Œ€ํ•ด์„œ ๋ณด๊ณ ๊ฐ€ ๋˜์—ˆ๋‹ค ํ•˜์ง€๋งŒ ์ž„์‹ ์ค‘ ๋‹คํ˜•์„ฑ ๋ฐœ์ง„. , (polymorphic eruption of pregnancy),25 ๊ฐ์—ผ์„ฑ ๊ฐ„ ์—ผ,9์ž๊ฐ€๋ฉด์—ญ์„ฑ์ด ์•„๋‹Œ ๊ฐ‘์ƒ์„  ์งˆํ™˜,26ํ˜ˆ์•ก์•”,27์ž๊ถ์•” ๋“ฑ10 ์ž๊ฐ€๋ฉด์—ญ์งˆํ™˜์ด ์•„๋‹Œ ๋‹ค๋ฅธ ์งˆ๋ณ‘๊ณผ microchimerism ์˜ ์—ฐ๊ด€์„ฑ์— ๋Œ€ํ•œ ์ฆ๊ฑฐ๋“ค๋„ ๊ณ„์† ๋ฐํ˜€์ง€๊ณ  ์žˆ๋‹ค ์ด. ๋Ÿฐ ์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋“ค์€ microchimerism์ด ์ž๊ฐ€๋ฉด์—ญ ์งˆํ™˜ ์˜ ๋ณ‘์ธ์— ์ง์ ‘ ๊ด€๋ จ๋œ๋‹ค๊ธฐ ๋ณด๋‹ค๋Š” ์งˆ๋ณ‘์˜ ๊ฒฐ๊ณผ๋ฌผ๋กœ microchimerism์ด ๋‚˜ํƒ€๋‚˜๋Š” ๊ฒƒ์ด๋ฉฐ ์‚ฐ๋ชจ์˜ ํ˜ˆ์•ก, ์ˆœํ™˜์œผ๋กœ ์ด๋™๋œ ํƒœ์•„์ธก ์„ธํฌ๋“ค์ด ๋‹ค์–‘ํ•œ ์กฐ์ง์œผ๋กœ ์˜ ๋ถ„ํ™”๋  ๊ฐ€๋Šฅ์„ฑ์„ ์ œ์‹œํ•˜๊ณ  ์žˆ๋‹ค๊ณ  ํ•˜๊ฒ ๋‹ค ์ตœ๊ทผ. ๋“ฑ ์— ์˜ํ•ด ์™€ ๋ฉด์—ญ์กฐ์ง Khosrotehrani (2004) FISH ํ™”ํ•™๋ฒ• (immunohistochemistry)์„ ๊ฒฐํ•ฉํ•œ microc-himerism์— ๋Œ€ํ•œ ์—ฐ๊ตฌ ๋ณด๊ณ ๋Š” ํƒœ์•„ ์„ธํฌ์˜ ๋‹ค์–‘ํ•œ ๋ถ„ ํ™”๋Šฅ๋ ฅ์€ ์ž„์‹  ํ›„์— ์˜ค๋žœ ๊ธฐ๊ฐ„ ์ƒ์กดํ•˜๋Š” ํƒœ์•„์„ธํฌ๊ฐ€ ์ค„ ๊ธฐ์„ธํฌ(stem cell)์ผ ๊ฐ€๋Šฅ์„ฑ์„ ๋†’๊ฒŒ ์‹œ์‚ฌํ•˜๊ณ  ์žˆ์œผ๋ฉฐ,5 ์ตœ๊ทผ ์ œ๋Œ€ํ˜ˆ์„ ๊ฐ€์ง€๊ณ  ์ง„ํ–‰๋˜๋Š” ์ค„๊ธฐ์„ธํฌ ์—ฐ๊ตฌ์— ์ค‘์š” ํ•œ ๊ทผ๊ฑฐ๋ฅผ ์ œ์‹œํ•œ๋‹ค๊ณ  ํ•˜๊ฒ ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๊ฒฐ๊ณผ๋Š” ๋‚จ์ž ์•„๊ธฐ๋ฅผ ์ถœ์‚ฐํ•œ ๊ฒฝํ—˜์ด ์žˆ๋Š” ์ž๊ถ๋‚ด๋ง‰์ฆ ํ™˜์ž์˜ ๋‚œ์†Œ์—์„œ๋Š” ํƒœ์•„ ์„ธํฌ๊ฐ€ ๊ด€์ฐฐ๋˜๊ณ  ์ถœ์‚ฐ๋ ฅ์ด ์—†๋Š” ๋Œ€์กฐ๊ตฐ์˜ ์ž๊ถ๋‚ด๋ง‰์ฆ ํ™˜์ž์˜ ๋‚œ์†Œ ์กฐ ์ง์—์„œ๋Š” ํƒœ์•„ ์„ธํฌ๊ฐ€ ๊ด€์ฐฐ๋˜์ง€ ์•Š์œผ๋ฏ€๋กœ ํƒœ์•„ ์„ธํฌ ์˜ michrochimerismํ˜„์ƒ์€ ์ถœ์‚ฐํ•œ ๊ฒฝํ—˜์ด ์žˆ๋Š” ์—ฌ์„ฑ ์˜ ์ž๊ถ๋‚ด๋ง‰์ฆ๊ณผ ์ผ์ •ํ•œ ์—ฐ๊ด€์„ฑ์ด ์žˆ์Œ์„ ์‹œ์‚ฌํ•œ๋‹ค ์ฆ‰. , ์ž„์‹  ์ „๊ณผ ํ›„์— ์ƒ๊ธฐ๋Š” ๋‹ค๋ฅธ ์กฐ๊ฑด์€ ์ž„์‹  ํ›„์˜ ์ž๊ถ๋‚ด๋ง‰ ์ฆ์ด ์ง€๊ธˆ๊นŒ์ง€ ๋ฐํ˜€์ง„ ์›์ธ ์ด์™ธ์— ์ถ”๊ฐ€์ ์œผ๋กœ ๋‹ค๋ฅธ ๊ธฐ ์ „์ด ์กด์žฌํ•˜๋Š” ๊ฒƒ์€ ์•„๋‹Œ๊ฐ€ ํ•˜๋Š” ์ถ”์ธก์ด ๊ฐ€๋Šฅํ•˜๋ฉฐ ์ž„์‹ , ์ค‘์— ํƒœ์•„์—๊ฒŒ์„œ ์ด๋™๋œ ํƒœ์•„ ์„ธํฌ๊ฐ€ ์ž„์‹  ํ›„์˜ ๋‚œ์†Œ์— ์„œ ์ง€์†๋˜๋ฉฐ ๋‚œ์†Œ์—์„œ ๋ฐœ์ƒํ•˜๋Š” ์ž๊ถ๋‚ด๋ง‰์ฆ์˜ ๋ฐœ์ƒ์ด๋‚˜ ์ง„ํ–‰์— ์—ฐ๊ด€๋  ์ˆ˜ ์žˆ๋Š” ๊ฐ€๋Šฅ์„ฑ์„ ์ƒ๊ฐํ•  ์ˆ˜ ์žˆ๋‹ค. ํ•˜์ง€๋งŒ ๋ณธ ์—ฐ๊ตฌ์—์„œ, microchimerism์ด ์—†๋Š” ๋Œ€์กฐ ๊ตฐ์˜ ๊ฒฝ์šฐ์—๋„ ์ž๊ถ๋‚ด๋ง‰์ฆ์ด ๋ฐœ์ƒ๋œ ๊ฒƒ์„ ํ™•์ธํ•˜์˜€๊ธฐ ๋•Œ๋ฌธ์— microchimerism๊ณผ ์ž๊ถ๋‚ด๋ง‰์ฆ์˜ ๊ด€๋ จ์„ฑ์„ ํ™•

(6)

์ธํ•˜๊ธฐ ์œ„ํ•ด์„œ๋Š” ๋” ๋งŽ์€ ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ ์—ฐ๊ตฌ๊ตฐ๊ณผ ๋Œ€์กฐ๊ตฐ์„ ์„ธ๋ถ„ํ•˜์—ฌ ์ถ”๊ฐ€์ ์ธ ์—ฐ๊ตฌ๋ฅผ ์‹œํ–‰ํ•˜๋Š” ๊ฒƒ์ด ํ•„ ์š”ํ•˜๋‹ค ๋˜ํ•œ ๋ณธ ์—ฐ๊ตฌ๋Š” ์—ฐ๊ตฌ๊ตฐ์˜ ๋‚œ์†Œ์—์„œ ๋ฐœ๊ฒฌ๋œ. , ์„ธํฌ๋“ค์˜ ๊ธฐ์›์„ ์•Œ ์ˆ˜ ์žˆ๋Š” ๋ฉด์—ญ์กฐ์ง microchimerism ํ•™์  ๋ถ„์„์ด ์—†์–ด ์ž๊ถ๋‚ด๋ง‰์ฆ์—์„œ์˜ michrochimerism ์„ธํฌ์˜ ์—ญํ• ์— ๋Œ€ํ•œ ์ถ”์ธก์— ์ค‘์š”ํ•œ ํ•œ๊ณ„์ ์ด ์žˆ์œผ๋ฉฐ, ์กฐ์ง์—์„œ ๋ถ„ํ™”๊ฐ€ ์ด๋ฃจ์–ด์ง„ ํƒœ์•„ microchimerism ์„ธ ํฌ๊ฐ€ ๋‹ค๋ฅธ ์ฃผ๋ณ€ ์„ธํฌ์™€ ๊ฐ™์€ ๊ธฐ๋Šฅ์„ ํ•˜๋Š”์ง€๋Š” ์—ฌ๋ถ€๋Š” ์•„์ง๊นŒ์ง€ ์˜๋ฌธ์ ์œผ๋กœ ๋‚จ์•„ ์žˆ์–ด์„œ ์ด์— ๋Œ€ํ•ด์„œ๋Š” ์ถ”ํ›„ ์˜ ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค ๊ทธ๋ฆฌ๊ณ  ํƒœ์•„์„ธํฌ. ์—์„œ ๋ฐœ๊ฒฌ๋˜๋Š” ํƒœ์•„์„ธํฌ์˜ ํŠน์ง•์— ๋Œ€ microchimerism ํ•œ ์—ฐ๊ตฌ์™€ ์—ฌ๋Ÿฌ ๊ฐ€์ง€ ๋‹ค์–‘ํ•˜๊ฒŒ ๋ถ„ํ™”ํ•˜๋Š” ์ •ํ™•ํ•œ ๊ธฐ์ „์„ ์•Œ์•„๋‚ด๋Š” ๊ฒƒ๋„ ์•ž์œผ๋กœ์˜ ๊ณผ์ œ๊ฐ€ ๋  ๊ฒƒ์ด๋‹ค. ๊ฒฐ๋ก ์ ์œผ๋กœ ๋ณธ ์—ฐ๊ตฌ์—์„œ ํŒŒ๋ผํ•€ ๊ณ ์ •๋œ ๋‚œ์†Œ ์กฐ์ง์˜, ๊ฐ€ ์„ฑ๊ณต์ ์œผ๋กœ ์‹œํ–‰๋˜์—ˆ๋‹ค ๋˜ํ•œ ์ž„์‹  ์ค‘ ๋ชจ์ฒด์˜ FISH . , ์ˆœํ™˜์œผ๋กœ ์ด๋™๋œ ํƒœ์•„์ธก microchimerism์„ธํฌ๊ฐ€ ์ž๊ถ ๋‚ด๋ง‰์ฆ๊ณผ ๊ฐ™์€ ์—ฌ์„ฑ์—์„œ ํ˜ธ๋ฐœํ•˜๋Š” ์งˆํ™˜์— ์กด์žฌํ•˜๊ณ  ์žˆ ์Œ์ด ํ™•์ธ๋˜์—ˆ๋‹ค ์ด๋Ÿฌํ•œ ํƒœ์•„์ธก. microchimerism์„ธํฌ ๊ฐ€ ์งˆ๋ณ‘์˜ ๋ฐœ์ƒ์— ๊ด€๋ จ๋˜๋Š”์ง€์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ๋”์šฑ ํ•„์š” ํ•˜๋‹ค๊ณ  ํ•˜๊ฒ ๋‹ค.

์ฐธ๊ณ ๋ฌธํ—Œ

1. Liegeois A, Escourrou J, Ohvre E, Charreire J. Michrochimerism: a stable state of low-ratio proliferation of allogeneic bone marrow. Transplant Proc 1977; 9: 273-6.

2. Agriga H, Ohto H, Burch MP, et al. Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. Transfusion 2001; 41: 1524-30.

3. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acsd Sci U S A 1996; 93: 705-8. 4. Lo YM, Patel P, Sampietro M, Gillmer MD, Fleming KA, Wainscoat JS. Detection of single-copy fetal DNA sequence from maternal blood. Lancet 1990; 335: 1463-4.

5. Khosrotehrani K, Johnson KL, Cha DH, Salomon RN, Bianchi DW. Transfer of fetal cells with multilineage potential to maternal tissue. JAMA 2004; 292: 75-80.

6. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, et al. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet 1998; 351: 559-62.

7. Artlett CM, Smith JB, Jimenez SA. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med 1998; 338: 1186-91.

8. Johnson KL, Nelson JL, Furst DE, McSweeney PA, Roberts DJ, Zhen DK, et al. Fetal cell microchimerism in tissue from multiple sites in women with systemic sclerosis. Arthritis Rheum 2001; 44: 1848-54. 9. Johnson KL, Samura O, Nelson JL, McDonnell WM, Bianchi DW. Significant fetal cell microchimerism in a nontransfused woman with hepatitis C: Evidence of long-term survival and expansion. Hepatology 2002; 36: 1295-7.

10. Cha D, Khosrotehrani K, Kim Y, Stroh H, Bianchi DW, Johnson KL. Cervical cancer and microchimerism. Obstet Gynecol 2003; 102: 774-81.

11. Goldman MA, Cramer DW. The epidermiology of endometriosis. Prog Clin Biol Res 1990; 323: 15-31.

12. Koninckx PR, et al. Implantation versus infiltration: the Samson versus the endometriotic disease theory. Gynecol Obstet Invest 1999; 47: 3-9.

13. Gleicher N, el-Roeiy A, Confino E, Friberg J. Is endometriosis an autoimmune disease? Obstet Gynecol 1990; 70: 115-22. 14. Nothnick WB. Treating endometriosis as an autoimmune disease.

Fertil Steril 2001; 76: 223-31.

15. Johnson KL, Zhen DK, Bianchi DW. The use of fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections for the study of microchimerism. Biotechniques 2000; 29: 1220-4. 16. Johnson KL, Nath J, Fluorescence in situ hybridization (FISH): DNA

probe production and hybridization criteria. Biotech Histochem 1998; 73: 6-22.

17. Srivatsa B, Srivatsa S, Johnson KL, Bianchi DW. Maternal cell microchimerism in newborn tissues. J Pediatr 2003; 142: 31-5. 18. Lambert NC, Lo YM, Erickson TD, et al. Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? a quantitative answer. Blood 2002; 100: 2845-51. 19. Artlett CM, Miller FW, Rider LG. Persistent maternally derived

peripheral microchimerism is associated with juvenile idiopathic inflammatory myopathies. Rheumatology (Oxford) 2001; 40: 1279-84. 20. Ando T, Imaizumi M, Graves PN, Unger P, Davies TF. Intrathyroidal fetal microchimerism in Gravesโ€™ disease. J Clin Endocrinol Metab 2002; 87: 3315-20.

21. Klintschar M, Schwaiger P, Mannweiler S, Regauer S, Kleiber M. Evidence of fetal microchimerism in Hashimotoโ€™s thyroiditis. J Clin Endocrinol Metab 2001; 86: 2494-8.

22. Endo Y, Negishi I, Ishikawa O. Possible contribution of microchi-merism to the pathogenesis of Sjogrenโ€™s syndrome. Rheumatology 2002; 41: 490-5.

23. Fanning PA, Jonsson JR, Clouston AD, Edwards-Smith C, Balderson GA, Macdonald GA, et al. Detection of male DNA in the liver of female patients with primary biliary cirrhosis. J Hepatol 2000; 33: 690-5.

24. Johnson KL, McAlindon TE, Mulcahy E, Bianchi DW. Microchi-merism in a female patient with systemic lupus erythematosus. Arthritis Rheum 2001; 44: 2107-11.

25. Aractingi S, Berkane N, Bertheau P, Le Goue C, Dausset J, Uzan S, et al. Fetal DNA in skin of polymorphic eruptions of pregnancy. Lancet 1998; 352: 1898-901.

26. Srivatsa B, Srivatsa S, Johnson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: A case-control study. Lancet 2001; 358: 2034-8. 27. Catlin EA, Roberts Jr JD, Erana R, Preffer FI, Ferry JA, Kelliher AS, et al. Transplacental transmission of natural killer-cell lymphoma. N Eng J Med 1999; 341: 85-91.

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๊ตญ๋ฌธ์ดˆ๋ก

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๋ชฉ์ : ์ถœ์‚ฐ์„ ๊ฒฝํ—˜ํ•œ ์—ฌ์„ฑ์—๊ฒŒ์„œ ๊ด€์ฐฐ๋˜๋Š”microchimerism์ด ํ”ํ•œ ๋ถ€์ธ๊ณผ ์งˆํ™˜์ด๋ฉด์„œ ์ž๊ฐ€๋ฉด์—ญ์งˆํ™˜์˜ ํŠน์ง•์„ ๊ฐ€์ง€๋Š” ์ž๊ถ ๋‚ด๋ง‰์ฆ ๋‚œ์†Œ ์กฐ์ง์—์„œ ๋ฐœ๊ฒฌ๋˜๋Š”๊ฐ€๋ฅผ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค. ์—ฐ๊ตฌ ๋ฐฉ๋ฒ•: ํ™˜์ž๊ตฐ์œผ๋กœ๋Š” ์ ์–ด๋„ ํ•œ ๋ช… ์ด์ƒ์˜ ๋‚จ์ž ์•„๊ธฐ๋ฅผ ์ถœ์‚ฐํ•œ ์‚ฐ๊ณผ๋ ฅ์ด ์žˆ๋Š” ์—ฌ์„ฑ์—์„œ ์ž๊ถ๋‚ด๋ง‰์ฆ์ด ์ง„๋‹จ๋œ ํ›„ ์ž๊ถ ๋‚ด๋ง‰์ข…์ ˆ์ œ์ˆ  ํ˜น์€ ๋‚œ์†Œ์ ˆ์ œ์ˆ ์„ ์‹œํ–‰ํ•œ ํ™˜์ž ๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€์œผ๋ฉฐ ๋Œ€์กฐ๊ตฐ์œผ๋กœ๋Š” ์ž„์‹ ์˜ ๊ฒฝ๋ ฅ์ด ์—†๋Š” ์—ฌ์„ฑ์—์„œ5 , ์ž๊ถ๋‚ด๋ง‰์ฆ์„ ์ง„๋‹จํ•˜๊ณ  ์ž๊ถ๋‚ด๋ง‰์ข…์ ˆ์ œ์ˆ  ํ˜น์€ ๋‚œ์†Œ์ ˆ์ œ์ˆ ์„ ์‹œํ–‰ํ•œ ํ™˜์ž ๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€๋‹ค ํƒœ์•„ ๊ธฐ์› ์„ธํฌ์˜5 . ์กด์žฌ ์—ฌ๋ถ€๋ฅผ ์•Œ์•„๋ณด๊ธฐ ์œ„ํ•˜์—ฌX์—ผ์ƒ‰์ฒด์™€Y์—ผ์ƒ‰์ฒด ํŠน์ด ์†Œ์‹์ž(probe)๋ฅผ ์ด์šฉํ•œ ํ˜•๊ด‘ ์ œ์ž๋ฆฌ๋ณดํ•ฉ๊ฒฐํ•ฉ๋ฒ•(fluorescence ์„ ์ด์šฉํ•˜์—ฌ ์กฐ์ง ์ ˆํŽธ์„ ๋ถ„์„ํ•˜์˜€๋‹ค in situ hybridization, FISH) .

๊ฒฐ๊ณผ: ํŒŒ๋ผํ•€ ๊ณ ์ •๋œ ๋‚œ์†Œ ์กฐ์ง์—์„œFISH๊ฐ€ ์„ฑ๊ณต์ ์œผ๋กœ ์‹œํ–‰๋˜์—ˆ๋‹ค ๋ช…์˜ ํ™˜์ž๊ตฐ ๋‚œ์†Œ ์กฐ์ง ๋ชจ๋‘ ํƒœ์•„์ธก ๋‚จ์„ฑ ์„ธํฌ๋“ค์ด. 5 ๋ฐœ๊ฒฌ๋˜์—ˆ๋‹ค ์ด์™€๋Š” ๋Œ€์กฐ์ ์œผ๋กœ ์ถœ์‚ฐ๋ ฅ์ด ์—†๋Š” ๋Œ€์กฐ๊ตฐ์˜ ๊ฒฝ์šฐ์—์„œ๋Š” ๋ช… ๋‚œ์†Œ ์กฐ์ง ๋ชจ๋‘์—์„œ ํƒœ์•„ ์„ธํฌ๊ฐ€ ๊ด€์ฐฐ๋˜์ง€ ์•Š. 5 ์•˜๋‹ค. ๊ฒฐ๋ก : ๋˜ํ•œ ์ž„์‹  ์ค‘ ๋ชจ์ฒด์˜ ์ˆœํ™˜์œผ๋กœ ์ด๋™๋œ ํƒœ์•„์ธก, microchimerism์„ธํฌ๊ฐ€ ์ž๊ถ๋‚ด๋ง‰์ฆ๊ณผ ๊ฐ™์€ ์—ฌ์„ฑ์—์„œ ํ˜ธ๋ฐœํ•˜๋Š” ์งˆํ™˜์— ์กด์žฌํ•˜๊ณ  ์žˆ์Œ์ด ํ™•์ธ๋˜์—ˆ๋‹ค ์ด๋Ÿฌํ•œ ํƒœ์•„์ธก. microchimerism์„ธํฌ๊ฐ€ ์งˆ๋ณ‘์˜ ๋ฐœ์ƒ์— ๊ด€๋ จ๋˜๋Š”์ง€์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ๋”์šฑ ํ•„์š” ํ•˜๋‹ค๊ณ  ํ•˜๊ฒ ๋‹ค. ์ค‘์‹ฌ๋‹จ์–ด:Microchimerism, ์ž๊ถ๋‚ด๋ง‰์ฆ

References

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