TrkB agonist antibody ameliorates fertility deficits in aged and cyclophosphamide-induced premature ovarian failure model mice

Xunsi Qin, Yue Zhao, Tianyi Zhang, Chenghong Yin, Jie Qiao, Wei Guo () and Bai Lu ()
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Xunsi Qin: Tsinghua University
Yue Zhao: Peking University Third Hospital
Tianyi Zhang: Tsinghua University
Chenghong Yin: Capital Medical University
Jie Qiao: Peking University Third Hospital
Wei Guo: Tsinghua University
Bai Lu: Tsinghua University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Premature ovarian failure (POF) is a leading cause of women’s infertility without effective treatment. Here we show that intravenous injection of Ab4B19, an agonistic antibody for the BDNF receptor TrkB, penetrates into ovarian follicles, activates TrkB signaling, and promotes ovary development. In both natural aging and cyclophosphamide-induced POF models, treatment with Ab4B19 completely reverses the reduction of pre-antral and antral follicles, and normalizes gonadal hormone. Ab4B19 also attenuates gonadotoxicity and inhibits apoptosis in cyclophosphamide-induced POF ovaries. Further, treatment with Ab4B19, but not BDNF, restores the number and quality of oocytes and enhances fertility. In human, BDNF levels are high in granulosa cells and TrkB levels increase in oocytes as they mature. Moreover, BDNF expression is down-regulated in follicles of aged women, and Ab4B19 activates TrkB signaling in human ovary tissue ex vivo. These results identify TrkB as a potential target for POF with differentiated mechanisms, and confirms superiority of TrkB activating antibody over BDNF as therapeutic agents.

Date: 2022
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DOI: 10.1038/s41467-022-28611-2

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