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Role of Visfatin in Restoration of Ovarian Aging and Fertility in the Mouse Aged 18 Months

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Abstract

The activation of dormant primordial follicles and ovarian angiogenesis has been attempted as a new treatment strategy for age-related ovarian aging. This study examined whether visfatin rescues age-related fertility decline in female mice aged 18 months, and whether this effect relates to the mTOR/PI3K signaling pathways for activation of primordial follicles and ovarian angiogenesis. Female mice were intraperitoneally injected with 0.1 ml of 500 ng/ml or 1000 ng/ml of visfatin three times at intervals of 2 days, and both ovaries were provided for H&E staining. In another experiment, the mice were superovulated with pregnant mare’s serum gonadotropin and human chorionic gonadotropin, and were mated with males. After 18 h, zygotes were collected and cultured for 4 days, and numbers and embryo developmental competency of zygotes retrieved were evaluated. The expression of mTOR/PI3K signaling pathway regulated genes (4EBP1, S6K1, and RPS6) and angiogenic factors (VEGF, visfatin, and SDF-1α) in the ovary were examined. As well, visfatin-treated mice were mated with male mice for 2 weeks, and the pregnancy outcome was monitored up to 3 weeks. Visfatin significantly increased the total numbers of follicles compared with control. Numbers of zygotes retrieved, blastocyst formation rate, and pregnancy rate were significantly increased at 500 ng/ml of visfatin (2.83%, 40.0%, and 80%, respectively) compared with control (0, 0, and no pregnancy). Ovarian expressions of S6K1, RPS6, VEGF, visfatin, and SDF-1α were significantly stimulated at 500 ng/ml of visfatin. These results show that visfatin treatment of an optimal dose rescues age-related decline in fertility, possibly by stimulating mTOR/PI3K signaling.

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Funding

This study was supported by a grant of the Basic Research Project, Ministry of Science and ICT and National Research Foundation, Republic of Korea (2017R1A2B4010859).

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Author notes

  1. Byung-Kyoo Park, Min Jung Park, Bo Sun Joo and Kyu-Sup Lee contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Gudeok-Ro 187, Seo-Gu, Busan, 49241, Republic of Korea

    Byung-Kyoo Park, Hwi Gon Kim, Si Eun Han & Kyu-Sup Lee

  2. The Korea Institute for Public Sperm Bank, Busan, Republic of Korea

    Min Jung Park & Bo Sun Joo

  3. Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea

    Chang-Woon Kim

  4. Infertility Institute, Pohang Women’s Hospital, Posco-daero 269, Buk-Ku, Pohang, Gyeongsangbuk-do, 37754, Republic of Korea

    Bo Sun Joo

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  1. Byung-Kyoo Park
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  2. Min Jung Park
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Corresponding authors

Correspondence to Bo Sun Joo or Kyu-Sup Lee.

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This study was approved by the institutional review board of Pusan National University Hospital, Korea. All animal experiments were conducted under the guidance for the Care and Use of Laboratory Animals of the National Institutes of Health, approved by the Pusan National University Hospital Institutional Animal Care and Use Committee.

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Park, BK., Park, M.J., Kim, H.G. et al. Role of Visfatin in Restoration of Ovarian Aging and Fertility in the Mouse Aged 18 Months. Reprod. Sci. 27, 681–689 (2020). https://doi.org/10.1007/s43032-019-00074-9

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  • DOI: https://doi.org/10.1007/s43032-019-00074-9

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