Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Amniotic Fluid Bisphenol A Level and Its Relationship with Pregnancy Outcomes

임신 중 내분비계 장애물질 Bisphenol A의 양수 내 농도와 임신결과와의 상관관계

  • Yoon, Jeong-Mi (Dept. of Obstetrics and Gynecology, Yonsei University College of Medicine) ;
  • Kwon, Ja-Young (Dept. of Obstetrics and Gynecology, Yonsei University College of Medicine) ;
  • Yoon, Yong-Dal (Dept. of Life Sciences, College of Natural Sciences, Hanyang University) ;
  • Kim, Sei-Kwang (Dept. of Obstetrics and Gynecology, Yonsei University College of Medicine)
  • 윤정미 (연세대학교 의과대학 산부인과학교실) ;
  • 권자영 (연세대학교 의과대학 산부인과학교실) ;
  • 윤용달 (한양대학교 자연과학대학 생명과학과) ;
  • 김세광 (연세대학교 의과대학 산부인과학교실)
  • Received : 2012.02.23
  • Accepted : 2012.06.20
  • Published : 2012.06.30
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Abstract

Bisphenol A (BPA), a chemical with weak estrogenic activity is reported to affect preimplantation embryos, fetuses and alter their postnatal development. This study amied to determine the relation between the levels of BPA in the amniotic fluid and pregnancy outcomes. ELISA was used to measure amniotic fluid BPA in 120 pregnant women who underwent genetic amniocentesis at 15~20 weeks gestation. The most common indication for amniocentesis was advanced maternal age (35 yrs or older). BPA was detected in all amniotic fluid. The range of amniotic fluid BPA concentrations was from 0.89 ng/mL to 37.13 ng/mL with a mean level of 7.24 ng/mL. We compared the means of amniotic fluid BPA concentrations according to maternal age (${\geq}35$ vs. <35 yrs), fetal sex (male vs. female), gestational age at birth (${\geq}37$ vs. <37 weeks), and infant birth weight (${\geq}2.5$ vs. <2.5 kg). No significant differences were found in these outcomes. This is the first report of amniotic fluid BPA levels in Korean pregnant women. Our findings suggest that BPA may not affect the pregnancy outcomes such as fetal sex, preterm delivery and low birth weight. Whether prenatal exposure to BPA can have teratogenic effect on developing embryo needs to be studied.

Bisphenol A(BPA)는 약한 estrogen 활성도를 보이는 화학물질로서 착상 전 배아나 태아에 영향을 미쳐, 출생 후 그들의 신체발달에 변화를 초래한다고 알려져 있다. 본 연구는 인체에서 임신 중기에 양수 내 BPA 농도를 측정하였으며, 측정된 농도에 따라 임신결과에 영향을 미치는지 여부를 알아보고자 하였다. 임신 15주에서 20주 사이에 유전학적 적응증으로 양수천자 검사를 시행 받았던 120명의 임신부 양수를 연구대상으로 ELISA 방법으로 농도를 측정하였다. 양수천자의 가장 많은 적응증은 35세 이상의 고령 임신부였다. BPA는 모든 양수에서 검출이 가능하였으며, 그 농도는 최저치 0.89 ng/mL부터 최고치 37.13 ng/mL까지의 분포를 보였고, 평균치는 7.24 ng/mL이었다. 양수 내 BPA 농도가 여러 임신결과들과 관련성이 있는지를 알아보기 위해 임신부 나이 35세 이상 대 미만, 남자 태아 대 여자 태아, 분만 당시 재태 연령 37주 이상 대 미만, 출생 당시 신생아 체중 2.5 kg 이상 대 미만으로 각각 나누어, 두 군간에 농도를 비교한 결과, 통계학적으로 유의한 차이는 없었다. 본 연구는 한국인 임신부를 대상으로 최초로 양수 내 BPA 농도에 관한 보고이다. 본 연구결과 BPA 농도는 임신부 나이나 태아성별에 따라 차이를 보이지 않았으며, 조산이나 저체중아의 발생과도 관련이 없음을 알 수 있었다. 향후 산전 BPA 노출이 배발생에 영향을 미치는지에 대한 연구가 필요하다고 사료된다.

Keywords

References

  1. Ashby J, Tinwell H (1998) Uterotrophic activity of bisphenol A in the immature rat. Environ Health Perspect 106:719-720. https://doi.org/10.1289/ehp.98106719
  2. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE (1992) Evidence for decreasing quality of semen during past 50 years. Br Med J 305:609-613. https://doi.org/10.1136/bmj.305.6854.609
  3. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM (1997) Secondary sexual characteristics and menses in young girls seen in office practice: A study from the Pediatric Research in Office Settings network. Pediatrics 99: 505-512. https://doi.org/10.1542/peds.99.4.505
  4. Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenbergh JG, vom Saal FS (1999) Exposure to bisphenol A advances puberty. Nature 401:763-764. https://doi.org/10.1038/44517
  5. Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y (2002) Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod 17:2839-2841. https://doi.org/10.1093/humrep/17.11.2839
  6. Krishman AV, Stathis P, Permuth S, Tokes L, Feldman D (1993) Bisphenol A: An estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinol 132:2279-2286. https://doi.org/10.1210/en.132.6.2279
  7. Lee YJ, Ryu HY, Kim HK, Min CS, Lee JH, Kim E, Nam BH, Park JH, Jung JY, Jang DD, Park EY, Lee KH, Ma JY, Won HS, Im MW, Leem JH, Hong YC, Yoon HS (2008) Maternal and fetal exposure to bisphenol A in Korea. Reprod Toxicol 25:413-419. https://doi.org/10.1016/j.reprotox.2008.05.058
  8. Markey CM, Michaelson CL, Veson EC, Sonnenschein C, Soto AM (2001) The mouse uterotrophic assay: A re-evaluation of its validity in assessing the estrogenicity of bisphenol A. Environ Health Perspect 109: 55-60. https://doi.org/10.1289/ehp.0110955
  9. Nagel SC, vom Saal FS, Thayer KA, Dhar MG. Boechler M, Welshons WV (1997) Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ Health Perspect 105:70-76. https://doi.org/10.1289/ehp.9710570
  10. Nikula H, Talonpoika T, Kaleva M, Toppari J (1999) Inhibition of hCG-stimulated steroidogenesis in cultured mouse leddig tumor cell by bisphenol A and octylphenols. Toxicol Appl Pharmacol 157:166-173. https://doi.org/10.1006/taap.1999.8674
  11. Paulozzi LJ, Erickson JD, Jackson RJ (1997) Hypospadias trends in two US surveillance systems. Pediatrics 100: 831-834. https://doi.org/10.1542/peds.100.5.831
  12. Rubin BS, Murray MK, Damassa DA, King JC, Soto AM (2001) Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ Health Perspect 109:675-680. https://doi.org/10.1289/ehp.01109675
  13. Schconfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I (2002) Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect 110(11):A703-A707. https://doi.org/10.1289/ehp.021100703
  14. Steinmetz R, Brown NG, Allen DL, Bigsby RM, Ben- Jonathan N (1997) The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. Endocrinol 138:1780-1786. https://doi.org/10.1210/en.138.5.1780
  15. Strassburg CP, Strassburg A, Kneip S, Barut A, Tukey RH, Rodeck B, Manns MP (2002) Developmental aspects of human hepatic drug glucuronidation in young children and adults. Gut 50:259-265. https://doi.org/10.1136/gut.50.2.259
  16. Takahashi O, Oishi S (2000) Disposition of orally administered 2,2-bis (4-hydroxyphenyl) propane (bisphenol A) in pregrant rats and the placental transfer to fetus. Environ Health Perspect 108:931-935. https://doi.org/10.1289/ehp.00108931
  17. Takai Y, Tsutsumi O, Ikezuki Y, Kamei Y, Osuga Y, Yano T, Taketani Y (2001) Preimplantation exposure to bisphenol A advances postnatal development. Reprod Toxicol 15:71-74.
  18. Takeuchi T, Tsutsumi O (2002) Serum bisphenol A concentrations showed gender differences, possibly linked to androgen levels. Biochem Biophys Res Commun 291:76-78. https://doi.org/10.1006/bbrc.2002.6407
  19. Tida H, Maehara K, Doiguchi M, Mori T, Yamada F (2003) Bisphenol A-induced apoptosis of cultured rat Sertoli cells. Reprod Toxicol 17:457-464. https://doi.org/10.1016/S0890-6238(03)00034-0
  20. vom Saal FS, Cooke PS, Buchanan DL, Palanza P, Thayer KA, Nagel SC, Parmigiani S, Welshons WV (1998) A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior. Toxicol Ind Health 14:239-260. https://doi.org/10.1177/074823379801400115
  21. Vrijheid M, Dolk H, Armstrong B, Abramsky L, Bianchi F, Fazarinc I, Garne E, Ide R, Robert E, Scott JE, Stone D, Tenconi R (2002) Chromosomal congenital anomalies and residence near hazardous waste landfill sites. Lancet 359:320-322. https://doi.org/10.1016/S0140-6736(02)07531-1
  22. Yamada H, Furuta I, Kato EH, Kataoka S, Usuki Y, Kobashi G, Sata F, Kishi R, Fujimoto S (2002) Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester. Reprod Toxicol 16:735-739. https://doi.org/10.1016/S0890-6238(02)00051-5
  23. Yokota H, Iwano H, Endo M, Kobayashi T, Inoue A, Ikushiro S, Yuasa A (1999) Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver. Biochem J 340; 405-409. https://doi.org/10.1042/0264-6021:3400405
  24. Yoshida M, Shimomoto T, Katashima S, Watanabe G, Taya K, Maekawa A (2004) Maternal exposure to low doses of bisphenol A has no effects on development of female reproductive tract and uterine carcinogenesis in donryu rats. J Reprod Dev 50:349-360. https://doi.org/10.1262/jrd.50.349
  25. Zalko D, Soto AM, Dolo L, Dorio C, Rathahao E, Debrauwer L (2003) Biotransformation of bisphenol A in a mammalian model: Answers and new questions raised by low dose metabolic fate studies in pregnant CD1 mice. Environ Health Perspect 111:309-319.