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BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation.

Publication ,  Journal Article
Liu, B; Liu, Y; Li, S; Chen, P; Zhang, J; Feng, L
Published in: J Ovarian Res
April 27, 2023

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in ovarian function including follicle development and oocyte maturation, and embryonic development. However, whether BDNF treatment can reimpose ovarian aging and impaired fertility remains elusive. In this study, we investigated the reproductive outcomes of BDNF treatment and potential mechanisms in aged mice. METHOD: "Aged" mice (35-37 weeks old, n = 68) were treated with recombinant human BDNF protein (rhBDNF, 1 µg/200 µL) through daily intraperitoneal (IP) injection for 10 days with/without ovulation induction. Reproductive age mice (8-10 weeks old, n = 28) were treated with ANA 12 (a selective BDNF receptor, TrkB antagonist) through daily IP injection for 5 days with/without ovulation induction. Ovarian function was assessed by ovarian weight, number of follicles, and sex hormone productions. Following induction of ovulation, the number of total oocytes or abnormal oocytes, and blastocyst formation were assessed. Reproductive functions of the mice were evaluated, including pregnancy rate, mating duration for conception, implantation sites, litter size, and weight of offspring. Finally, the molecular mechanism of the effects of BDNF on ovarian cell functions in mice were examined by Western blot and immunofluorescence. RESULTS: rhBDNF treatment increased the ovarian weight, number of follicles, number and quality of oocytes including increased blastocysts formation, blood estrogen levels, and pregnancy rate in 35-37-week-old mice. Conversely, BDNF receptor antagonist, ANA 12, treatment decreased the ovarian volume and number of antral follicles and increased the proportion of abnormal oocytes in 8-10-week-old mice. We further demonstrated that BDNF treatment promoted ovarian cell proliferation as well as activation of TrkB and cyclinD1-creb signalling. CONCLUSION: We demonstrated that ten consecutive days of daily IP injection of rhBDNF rescued ovarian function in aged mice. Our results further indicate that TrkB and cyclin D1-creb signaling may underlie the BDNF function in ovaries. Targeting BDNF-TrkB signaling is a potential novel therapeutic strategy to reverse ovarian aging.

Duke Scholars

Published In

J Ovarian Res

DOI

EISSN

1757-2215

Publication Date

April 27, 2023

Volume

16

Issue

1

Start / End Page

83

Location

England

Related Subject Headings

  • Pregnancy
  • Ovary
  • Ovarian Follicle
  • Oocytes
  • Mice
  • Humans
  • Female
  • Cell Proliferation
  • Brain-Derived Neurotrophic Factor
  • Animals
 

Citation

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Liu, B., Liu, Y., Li, S., Chen, P., Zhang, J., & Feng, L. (2023). BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation. J Ovarian Res, 16(1), 83. https://doi.org/10.1186/s13048-023-01163-9
Liu, Bin, Yongjie Liu, Shuman Li, Pingping Chen, Jun Zhang, and Liping Feng. “BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation.J Ovarian Res 16, no. 1 (April 27, 2023): 83. https://doi.org/10.1186/s13048-023-01163-9.
Liu B, Liu Y, Li S, Chen P, Zhang J, Feng L. BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation. J Ovarian Res. 2023 Apr 27;16(1):83.
Liu, Bin, et al. “BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation.J Ovarian Res, vol. 16, no. 1, Apr. 2023, p. 83. Pubmed, doi:10.1186/s13048-023-01163-9.
Liu B, Liu Y, Li S, Chen P, Zhang J, Feng L. BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation. J Ovarian Res. 2023 Apr 27;16(1):83.
Journal cover image

Published In

J Ovarian Res

DOI

EISSN

1757-2215

Publication Date

April 27, 2023

Volume

16

Issue

1

Start / End Page

83

Location

England

Related Subject Headings

  • Pregnancy
  • Ovary
  • Ovarian Follicle
  • Oocytes
  • Mice
  • Humans
  • Female
  • Cell Proliferation
  • Brain-Derived Neurotrophic Factor
  • Animals