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The effect of mTOR activation and PTEN inhibition on human primordial follicle activation in ovarian tissue culture

  • Fertility Preservation
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Abstract

Purpose

The effect of PTEN inhibitor (Bpv(HOpic); Bpv) and mTOR activators (phosphatidic acid (PA) and propranolol (PP)), were evaluated on the activation and subsequent development of human primordial follicles in ovarian tissue culture.

Methods

Slow frozen-thawed human ovarian cortical strips were incubated for 24 h in different groups: (1) Control (base medium), (2) Bpv (100 µM), (3) PA (200 µM), (4) PA + PP (50 µm), and (5) Bpv + PA + PP. Afterward, the medium was exchanged, and all groups were cultured without stimulators for 6 additional days. The proportion of normal and degenerated follicles, estradiol secretion, and expression of RPS6, FOXO3a, and AKT proteins was evaluated and compared between groups.

Results

After 24 h of culture, there was no significant difference between the proportion of primordial and growing follicles in either of the experimental groups. This non-significant change was also observed for the phosphorylated protein to total protein ratios of RPS6, FOXO3a, and AKT proteins. After 7 days of culture, the proportion of the transitional follicles was significantly higher in comparison to the primordial follicles for the PA, PA + PP, and Bpv + PA + PP groups. The estradiol level was significantly higher on the last day compared to the first day, in PA, PA + PP, and Bpv + PA + PP groups. Hormonal secretion was significantly higher in the PA and PA + PP groups and lower in the Bpv and Bpv + PA + PP groups compared to the control on day 7 of culture.

Conclusion

Temporary in vitro treatment of human ovarian tissue with mTOR activators enhances the initiation of primordial follicle development and positively influences steroidogenesis after short-term culture.

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Funding

This research was financially supported by the Royan Institute.

Author information

Authors and Affiliations

  1. Department of Developmental Biology, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, ACECR, Tehran, Iran

    Zeinab Ghezelayagh

  2. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

    Zeinab Ghezelayagh, Naeimeh Sadat Abtahi & Bita Ebrahimi

  3. Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Mojtaba Rezazadeh Valojerdi

Authors
  1. Zeinab Ghezelayagh
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  2. Naeimeh Sadat Abtahi
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  3. Mojtaba Rezazadeh Valojerdi
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  4. Bita Ebrahimi
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Contributions

Zeinab Ghezelayagh: PhD student, investigation, methodology, formal analysis, writing—original draft.

Naeimeh Sadat Abtahi: Troubleshooting in the lab, data curation, follicular count, writing—review and editing.

Mojtaba Rezazadeh Valojerdi: Scientific adviser of the project, writing—review and editing.

Bita Ebrahimi: Supervision, conceptualization, project administration, writing—review and editing.

Corresponding author

Correspondence to Bita Ebrahimi.

Ethics declarations

Ethics approval

This study was approved by the Ethics Committee of Royan Institute (ethics code: IR.ACECR.ROYAN.REC.1396.212).

Consent to participate

Informed consent was received from all individual participants included in the study.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Key messages

In vitro activation of primordial follicles via various pharmacological compounds provides an alternative technique for fertility restoration. Here we indicate that in vitro treatment of human ovarian tissue with mTOR activators enhances the initiation of primordial follicle development and positively influences steroidogenesis.

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Ghezelayagh, Z., Abtahi, N.S., Rezazadeh Valojerdi, M. et al. The effect of mTOR activation and PTEN inhibition on human primordial follicle activation in ovarian tissue culture. J Assist Reprod Genet 39, 1739–1747 (2022). https://doi.org/10.1007/s10815-022-02537-6

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  • DOI: https://doi.org/10.1007/s10815-022-02537-6

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