실험적 마우스 모델에서 예측 불가능한 스트레스가 황체형성호르몬 수용체의 발현과 생식기능에 미치는 영향에 관한 연구

The Effects of Unpredictable Stress on the LHR Expression and Reproductive Functions in Mouse Models

  • Choi, Sung-Young (College of Veterinary Medicine, Kyungpook National University) ;
  • Park, Jin-Heum (College of Veterinary Medicine, Kyungpook National University) ;
  • Zhu, Yuxia (College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Young-Jong (College of Veterinary Medicine, Kyungpook National University) ;
  • Park, Jae-Ok (College of Veterinary Medicine, Kyungpook National University) ;
  • Moon, Changjong (College of Veterinary Medicine, Chonnam National University) ;
  • Shin, Taekyun (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Ahn, Meejung (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Kim, Suk-Soo (Department of Philosophy, Kyungpook National University) ;
  • Park, Young-Sik (Department of Animal Biotechnology, Kyungpook National University) ;
  • Chae, Hyung-Bok (College of Law, Kyungpook National University) ;
  • Kim, Tae-Kyun (Department of Agricultural Economics, Kyungpook National University) ;
  • Kim, Seung-Joon (College of Veterinary Medicine, Kyungpook National University)
  • 심사 : 2014.10.11
  • 발행 : 2014.10.31

초록

본 연구의 목적은 예측 불가능한 만성적인 스트레스가 생식기능과 황체형성호르몬 수용체의 발현에 미치는 영향을 알아보는 것이다. 9 주령 암컷 C57BL/6 마우스를 무작위로 선택하여 대조군과 스트레스군의 두 집단으로 분류하였다. 스트레스군은 35일 동안 하루에 두 번씩 12가지의 서로 다른 스트레스를 무작위로 선택하여 스트레스를 주었다. 대조군에 비하여 스트레스군에서 불안과 관련된 행동들이 유의성 있게 증가하였으며(P < 0.05), 스트레스를 받는 동안의 증체율 또한 유의성 있게 감소하였다(P < 0.01). 그리고 평균 산자수도 대조군에 비하여 스트레스 군에서 유의하게 감소함을 관찰 하였다(P < 0.01). 조직학적인 검사에서 일차, 이차 및 초기 성숙 난포의 비율이 대조군에 비해 스트레스 군에서 유의하게 감소한 반면(P < 0.05) 폐쇄 난포의 비율은 유의하게 증가하였다(P < 0.01). 면역조직화학적 검사를 통해 과립막세포와 황체세포의 황체형성호르몬 수용체 발현을 관찰한 결과, 대조군에 비해 스트레스군에서 그 발현이 감소하였고, 웨스턴 블롯을 통해 난소 내 황체형성호르몬 수용체의 단백질 양을 측정한 결과 또한 대조군에 비하여 스트레스군에서 유의하게 감소하였다(P < 0.05). 본 연구를 통해 난소의 황체형성호르몬 수용체는 예측 불가능한 스트레스에 의해 영향을 받으며, 변화된 황체형성호르몬 수용체가 난자의 난포 발육 불량과 생식기능의 이상에 영향을 미친다는 것을 실험적으로 증명하였다.

The objective of this study was to investigate the effect of chronic unpredictable stress on the reproductive function and ovarian luteinizing hormone receptor (LHR) expression. 9-week-old C57BL/6 female mice were randomly divided into two groups: control group and stressed group. Mice have been stressed twice a day for 35 days with 12 different stressors which were randomly selected. The results demonstrate that there is significant increase in the anxiety-related behaviors (P < 0.05), decrease body weight gain rate (P < 0.01) and decrease in the average of litter size in stressed mice compared with control group (P < 0.01). Furthermore, the rate of primary, secondary and early antral follicles in stressed mice significantly decreased (P < 0.05), whereas that of atretic follicles significantly increased compared with control mice (P < 0.01). The immunohistochemical analysis revealed that reduced LHR expression in granulosa cells of follicle and luteal cells of corpus luteum in response to chronic unpredictable stress. The western blot analysis revealed significantly decrease in LHR expression in the stressed mice ovaries compared with the control (P < 0.05). These results suggest that ovarian LHR expression affected by chronic unpredictable stress and the modulated ovarian LHR is responsible for ovarian follicular maldevelopment and reproductive dysfunction.

키워드

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