P53 Plays an Important Role in the Early Stage of Autologous Heterotopic Transplantation of Ovaries into the Backs of Mice

Transplant Proc. 2020 Jan-Feb;52(1):406-413. doi: 10.1016/j.transproceed.2019.11.028. Epub 2020 Jan 3.

Abstract

Background: Subcutaneous ovarian transplantation has recently begun receiving increased attention. Fourteen days after transplantation is used as an important time point for assessing the recovery of ovarian function. The goal of this study is to determine the expression of apoptotic genes in the ovary at this time.

Methods: This study investigated follicle development and the expression of 3 apoptosis genes (Bax, Bcl2, and P53) after mouse ovaries were transplanted. Seven-week-old mouse ovaries were autologously transplanted into back muscle. The ovaries were harvested on day 14, morphology was observed by hematoxylin and eosin staining, and the distribution of 3 proteins was observed by immunohistochemistry. TUNEL staining showed where apoptosis occurred in the ovary. Finally, RT-PCR/Western blotting was used to analyze the differential expression of mRNA/proteins between the transplantation group and the control group.

Results: The results revealed follicles at different stages at the edge of the grafts. In immunohistochemical experiments, BAX, BCL2, and P53 were found to be extensively expressed in the transplant group and the control group. P53 was strongly expressed in the medulla of transplanted ovaries. Bax was strongly expressed in the antral follicles of both groups. The results were consistent with the results of the TUNEL experiments. Three genes (Bax, Bcl2, and P53) were downregulated in the transplanted groups. The results showed that significant differences were detected in Bax and P53 mRNA expression levels between the transplanted groups and the control group (P < .01). Bcl2 expression was not significantly different, but the Bax/Bcl2 ratio increased. The results of the protein experiments were the same.

Conclusion: P53 may downregulate Bax in the early stage of transplantation. Follicle growth and atresia were regulated through modulation of Bcl2- and Bax-mediated apoptotic pathways in heterotopic ovarian transplantation.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Ovarian Follicle / metabolism*
  • Ovarian Follicle / pathology*
  • Ovary / metabolism*
  • Ovary / pathology*
  • Ovary / transplantation*
  • Transplantation, Autologous
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein