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Human amniotic epithelial cells inhibit granulosa cell apoptosis induced by chemotherapy and restore the fertility.

Zhang Q, Xu M, Yao X, Li T, Wang Q, Lai D - Stem Cell Res Ther (2015)

Bottom Line: Premature ovarian failure and insufficiency are significant long-term side-effects of chemotherapy for female cancer patients.Additionally, the ovarian function and fertility of mice were assessed via counts of follicles and mating experiments at 4 weeks after hAEC transplantation. hAECs significantly inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis induced by chemotherapeutics and reduced the inflammatory reaction in ovaries at 7 days after transplantation.These results suggest a potential molecular mechanism for the effective therapy of hAEC transplantation in chemotherapy-induced premature ovarian failure and insufficiency.

View Article: PubMed Central - PubMed

Affiliation: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. 10111010022@fudan.edu.cn.

ABSTRACT

Introduction: Premature ovarian failure and insufficiency are significant long-term side-effects of chemotherapy for female cancer patients. Recently, stem cell transplantation has been identified as a promising treatment for premature ovarian failure and insufficiency. We have previously demonstrated that human amniotic epithelial cells (hAECs) migrate into injured tissue and promote the recovery of ovarian function in chemoablated mice. However, the molecular mechanism guiding this process remains unclear.

Methods: To further investigate the effect of hAECs on chemotherapy-induced apoptosis, cultured primary hAECs were injected intravenously into mice treated with cyclophosphamide and busulphan. Apoptosis of granulosa cells was observed by TUNEL staining, and apoptosis-related gene expression was performed on ovarian tissue by real-time PCR and Western blot 7 days after hAEC transplantation. Additionally, the ovarian function and fertility of mice were assessed via counts of follicles and mating experiments at 4 weeks after hAEC transplantation.

Results: hAECs significantly inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis induced by chemotherapeutics and reduced the inflammatory reaction in ovaries at 7 days after transplantation. In addition, 4 weeks after transplantation, hAECs promoted the development of follicles and increased the number of cumulus oocyte complexes in chemoablated mice. Furthermore, hAECs improved ovarian mass and increased the number of follicles compared to those of the chemoablated group, and hAEC transplantation partially rescued the fertility of chemoablated mice.

Conclusions: hAEC transplantation promotes ovarian function by inhibiting tumor necrosis factor-alpha-mediated cell apoptosis and reducing inflammation in chemotherapy-induced premature ovarian failure. These results suggest a potential molecular mechanism for the effective therapy of hAEC transplantation in chemotherapy-induced premature ovarian failure and insufficiency.

No MeSH data available.


Related in: MedlinePlus

hAEC transplantation increased the number of ovarian follicles and restored the fertility of chemoablated mice. A Bar graph illustrating body weight of experimental and control groups following hAEC transplantation. B The ovarian weight in different groups at 28 days after hAEC transplantation. C Histological analysis of ovaries in different groups at 28 days after hAEC transplantation. D The number of different stage follicles counted at 28 days after hAEC transplantation. E Bar graph representing the number of pups per pregnancy at the end of mating. Data are mean ± SEM; *p < 0.05 versus Sham; #p < 0.05 versus Cy. Scale bars in c = 500 μm (a–c), 200 μm (d–f), 100 μm (g–i), 50 μm (j–l). Cy chemoablated group (n = 6; n = 10 in E), Cy + hAECs hAEC-treated group (n = 6; n = 10 in E), Sham sham group (n = 6; n = 5 in E)
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Fig6: hAEC transplantation increased the number of ovarian follicles and restored the fertility of chemoablated mice. A Bar graph illustrating body weight of experimental and control groups following hAEC transplantation. B The ovarian weight in different groups at 28 days after hAEC transplantation. C Histological analysis of ovaries in different groups at 28 days after hAEC transplantation. D The number of different stage follicles counted at 28 days after hAEC transplantation. E Bar graph representing the number of pups per pregnancy at the end of mating. Data are mean ± SEM; *p < 0.05 versus Sham; #p < 0.05 versus Cy. Scale bars in c = 500 μm (a–c), 200 μm (d–f), 100 μm (g–i), 50 μm (j–l). Cy chemoablated group (n = 6; n = 10 in E), Cy + hAECs hAEC-treated group (n = 6; n = 10 in E), Sham sham group (n = 6; n = 5 in E)

Mentions: To investigate the long-term effects of hAEC transplantation on ovarian function, we recorded changes in body weight at various time points following hAEC transplantation. The body weight and ovarian weight of mice in the chemoablated group were significantly lower than those in the sham group. While hAEC transplantation had no obvious effect on body weight (Fig. 6A), the ovarian weight in the hAEC-treated group was significantly higher than that in the chemoablated group at 28 days following transplantation (Fig. 6B, p < 0.05). Histologic evaluation indicated that ovaries were severely atrophic, and the population of each stage of follicles was significantly decreased in chemoablated mice (Fig. 6C). hAEC transplantation greatly increased the number of healthy follicles, especially secondary and mature follicles, and attenuated the number of follicular atresia compared to the chemoablated group (Fig. 6C and D, p < 0.05).Fig. 6


Human amniotic epithelial cells inhibit granulosa cell apoptosis induced by chemotherapy and restore the fertility.

Zhang Q, Xu M, Yao X, Li T, Wang Q, Lai D - Stem Cell Res Ther (2015)

hAEC transplantation increased the number of ovarian follicles and restored the fertility of chemoablated mice. A Bar graph illustrating body weight of experimental and control groups following hAEC transplantation. B The ovarian weight in different groups at 28 days after hAEC transplantation. C Histological analysis of ovaries in different groups at 28 days after hAEC transplantation. D The number of different stage follicles counted at 28 days after hAEC transplantation. E Bar graph representing the number of pups per pregnancy at the end of mating. Data are mean ± SEM; *p < 0.05 versus Sham; #p < 0.05 versus Cy. Scale bars in c = 500 μm (a–c), 200 μm (d–f), 100 μm (g–i), 50 μm (j–l). Cy chemoablated group (n = 6; n = 10 in E), Cy + hAECs hAEC-treated group (n = 6; n = 10 in E), Sham sham group (n = 6; n = 5 in E)
© Copyright Policy - OpenAccess
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Fig6: hAEC transplantation increased the number of ovarian follicles and restored the fertility of chemoablated mice. A Bar graph illustrating body weight of experimental and control groups following hAEC transplantation. B The ovarian weight in different groups at 28 days after hAEC transplantation. C Histological analysis of ovaries in different groups at 28 days after hAEC transplantation. D The number of different stage follicles counted at 28 days after hAEC transplantation. E Bar graph representing the number of pups per pregnancy at the end of mating. Data are mean ± SEM; *p < 0.05 versus Sham; #p < 0.05 versus Cy. Scale bars in c = 500 μm (a–c), 200 μm (d–f), 100 μm (g–i), 50 μm (j–l). Cy chemoablated group (n = 6; n = 10 in E), Cy + hAECs hAEC-treated group (n = 6; n = 10 in E), Sham sham group (n = 6; n = 5 in E)
Mentions: To investigate the long-term effects of hAEC transplantation on ovarian function, we recorded changes in body weight at various time points following hAEC transplantation. The body weight and ovarian weight of mice in the chemoablated group were significantly lower than those in the sham group. While hAEC transplantation had no obvious effect on body weight (Fig. 6A), the ovarian weight in the hAEC-treated group was significantly higher than that in the chemoablated group at 28 days following transplantation (Fig. 6B, p < 0.05). Histologic evaluation indicated that ovaries were severely atrophic, and the population of each stage of follicles was significantly decreased in chemoablated mice (Fig. 6C). hAEC transplantation greatly increased the number of healthy follicles, especially secondary and mature follicles, and attenuated the number of follicular atresia compared to the chemoablated group (Fig. 6C and D, p < 0.05).Fig. 6

Bottom Line: Premature ovarian failure and insufficiency are significant long-term side-effects of chemotherapy for female cancer patients.Additionally, the ovarian function and fertility of mice were assessed via counts of follicles and mating experiments at 4 weeks after hAEC transplantation. hAECs significantly inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis induced by chemotherapeutics and reduced the inflammatory reaction in ovaries at 7 days after transplantation.These results suggest a potential molecular mechanism for the effective therapy of hAEC transplantation in chemotherapy-induced premature ovarian failure and insufficiency.

View Article: PubMed Central - PubMed

Affiliation: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. 10111010022@fudan.edu.cn.

ABSTRACT

Introduction: Premature ovarian failure and insufficiency are significant long-term side-effects of chemotherapy for female cancer patients. Recently, stem cell transplantation has been identified as a promising treatment for premature ovarian failure and insufficiency. We have previously demonstrated that human amniotic epithelial cells (hAECs) migrate into injured tissue and promote the recovery of ovarian function in chemoablated mice. However, the molecular mechanism guiding this process remains unclear.

Methods: To further investigate the effect of hAECs on chemotherapy-induced apoptosis, cultured primary hAECs were injected intravenously into mice treated with cyclophosphamide and busulphan. Apoptosis of granulosa cells was observed by TUNEL staining, and apoptosis-related gene expression was performed on ovarian tissue by real-time PCR and Western blot 7 days after hAEC transplantation. Additionally, the ovarian function and fertility of mice were assessed via counts of follicles and mating experiments at 4 weeks after hAEC transplantation.

Results: hAECs significantly inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis induced by chemotherapeutics and reduced the inflammatory reaction in ovaries at 7 days after transplantation. In addition, 4 weeks after transplantation, hAECs promoted the development of follicles and increased the number of cumulus oocyte complexes in chemoablated mice. Furthermore, hAECs improved ovarian mass and increased the number of follicles compared to those of the chemoablated group, and hAEC transplantation partially rescued the fertility of chemoablated mice.

Conclusions: hAEC transplantation promotes ovarian function by inhibiting tumor necrosis factor-alpha-mediated cell apoptosis and reducing inflammation in chemotherapy-induced premature ovarian failure. These results suggest a potential molecular mechanism for the effective therapy of hAEC transplantation in chemotherapy-induced premature ovarian failure and insufficiency.

No MeSH data available.


Related in: MedlinePlus