Overexpression of Rap1B alleviate central precocious puberty and neurodevelopmental damage

Introduction: The central precocious puberty (CPP) in children and adolescents can adversely impact their overall well-being, affecting both their physical and psychological health. Whether Rap1B can mitigate the development of CPP remains unknown.

Methods: The expression of Rap1B was investigated through a comprehensive bioinformatics analysis. Precocious puberty model in rats was established through high-fat feeding (HFD), and further injected AAV-Rap1B. Then, HE staining, vaginal exfoliated cell smear and Other methods were used to explore the incidence of precocious puberty in rats in each group. In addition, Western blot, RT-qPCR, and IHC was used to detect the expression of GnRH, GnRHR, Kiss1, Kiss1R, NeuN, BDNF, TH, AVP. The contents of LH, FSH, E2, T, and AMH in serum of rats were detected by ELISA. The Rap1B cell line was constructed at the cellular level to explore the effects of FFA(OA + PA) induction on cell proliferation, Apoptosis and inflammation.

Results: The expression of Rap1B was significantly up-regulated in overexpressing MKRN3 cells, where overexpressing MKRN3 can alleviate the occurrence of CPP. Overexpression of Rap1B alleviates HFD-induced CPP models, including reduce the content of LH, FSH, E2, T, and AMH in serum, and inhibit the expression of GnRH, Kiss1 and Kiss1R in hypothalamus, and alleviates hypothalamus injury. Furthermore, overexpression of Rap1B in the GT1-7 cell. Overexpression of Rap1B can significantly reverse FFA damage to GT1-7 cells and reduce FFA-induced increase of inflammatory factors (IL-6, IL-1β and TNF-α) in GT1-7 cells.

Conclusion: This study indicated that overexpression of Rap1B alleviate CPP and neurodevelopmental damage. Our study offers a new approach for the treatment of CPP.

Central precocious puberty; High fat diet; Neurodevelopmental damage; Rap1B.