Fst, also known as follistatin, is a member of the transforming growth factor-β (TGF-β) superfamily and an inhibitor of follicle-stimulating hormone. It plays important roles in animal reproduction, such as regulating oocyte maturation and early embryonic development. It is also involved in the TGF-β/SMAD pathway [1].

In buffalo, Fst is enriched in the ovary and its expression is up-regulated in MII buffalo oocytes compared to the GV stage. Adding the PCD3.1-EGFP-FST vector to the maturation fluid promoted the in vitro maturation rate of buffalo oocytes and the blastocyst rate of embryos cultured in vitro. Interfering with Fst expression in cumulus cells led to abnormal mitochondria location in oocytes, reduced cumulus expansion area, and decreased cleavage and blastocyst rates after parthenogenetic activation. Overexpression of Fst could up-regulate the expression level of apoptosis suppressor gene Bcl-2 and TGF-β/SMAD pathway-related genes TGF-β, SMAD2, and SMAD3, while down-regulating SMAD4 and pro-apoptotic gene BAX [1]. In mice, Fst was up-regulated in A-fiber sensory neurons after spinal nerve ligation. Inhibition or deletion of Fst alleviated neuropathic pain and reduced nociceptive neuron hyperexcitability, while injection or overexpression of Fst induced pain hypersensitivity. Fst binds directly to the insulin-like growth factor-1 receptor (IGF1R), and blocking this interaction attenuated Nav1.7-mediated neuronal hyperexcitability and neuropathic pain [2].

In conclusion, Fst has essential functions in animal reproduction, regulating oocyte-related processes through the TGF-β/SMAD pathway. In addition, it is involved in neuropathic pain in mice, potentially serving as a target for treatment. These findings from in vivo studies in buffalo and mice help to understand the biological functions of Fst in reproduction-related and pain-related biological processes.

References:

1. Wang, Haoxin, Chen, Weili, Shen, Penglei, Shi, Deshun, Lu, Fenghua. 2023. Follistatin (FST) is expressed in buffalo (Bubalus bubalis) ovarian follicles and promotes oocyte maturation and early embryonic development. In Reproduction in domestic animals = Zuchthygiene, 58, 1718-1731. doi:10.1111/rda.14490. https://pubmed.ncbi.nlm.nih.gov/37917549/

2. Jiang, Bao-Chun, Ling, Yue-Juan, Xu, Meng-Lin, Ji, Ru-Rong, Gao, Yong-Jing. 2024. Follistatin drives neuropathic pain in mice through IGF1R signaling in nociceptive neurons. In Science translational medicine, 16, eadi1564. doi:10.1126/scitranslmed.adi1564. https://pubmed.ncbi.nlm.nih.gov/39413164/