한빛사논문
Danbi Lee1 · Jungho Ahn2 · Hwa Seon Koo3* · Youn‑Jung Kang2*
1 Department of Biomedical Science, School of Life Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
2 Department of Biochemistry, School of Medicine, Research Institute for Basic Medical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
3 CHA Fertility Center Bundang, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
* Corresponding authors : Correspondence to Hwa Seon Koo or Youn-Jung Kang.
Abstract
Adequate endometrial growth is a critical factor for successful embryo implantation and pregnancy maintenance. We previously reported the efficacy of intrauterine administration of botulinum toxin A (BoTA) in improving the endometrial angiogenesis and the rates of embryo implantation. Here, we further evaluated its potent therapeutic effects on the uterine structural and functional repair and elucidated underlying molecular regulatory mechanisms. This study demonstrated that a murine model of thin endometrium was successfully established by displaying dramatically decreased endometrial thickness and the rates of embryo implantation compared to normal endometrium. Interestingly, the expressions of insulin-like growth factor binding protein-3 (IGFBP3) and an active 35 kDa-form of osteopontin (OPN) were significantly reduced in thin endometrium, which were almost fully restored by intrauterine BoTA administration. Neutralization of BoTA-induced IGFBP3 subsequently suppressed proteolytic cleavage of OPN, exhibiting un-recovered endometrial thickness even in the presence of BoTA administration, suggesting that BoTA-induced endometrial regeneration might be mediated by IGFBP3-dependent OPN proteolytic cleavage. Our findings suggest that intrauterine BoTA administration improves the endometrial environment in our murine model with thin endometrium by increasing endometrial receptivity and angiogenesis in a manner dependent on the regulatory effect of IGFBP3 on OPN proteolytic cleavage, proposing BoTA as an efficient therapeutic strategy for the patients with thin endometrium.
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