Optimized platelet rich plasma releasate (O-rPRP) repairs galactosemia-induced ovarian follicular loss in rats by activating mTOR signaling and inhibiting apoptosis

Platelet rich plasma contains a collection of growth factors, and an optimal formulation, named O-rPRP, contains the highest possible concentration of growth factors. Challenging the healing power of O-rPRP in a high-galactose diet-induced premature ovarian insufficiency (POI) experimental rat model. Rats were divided into four groups of ten rats each and treated for four week as follows; 1) the control group, fed with normal diet and received intraperitoneal (i.p.) injection of PBS once/week; 2) the POI group, fed with galactose diet (50%) and received PBS (i.p.) once/week; 3) the POI/O-rPRP group, fed a 50% galactose diet and received O-rPRP (i.p.) once/week; 4) the O-rPRP group (negative control), fed with a normal diet and received O-rPRP (i.p.) once/week. The levels of galactose, follicle stimulating hormone, 17 β-estradiol, anti-mullerian hormone and inhibin B were measured in serum samples. Western blotting and quantitative real-time PCR assays were employed to investigate the levels of miR-223, β1 integrin, p70S6k and MCL-1 in ovarian tissues. After O-rPRP treatment, β1 integrin expression was enhanced, and miR-223 expression was decreased. Unlike the untreated galactose group, in the group treated with O-rPRP, p70S6k and MCL-1 expression levels were increased, indicating that the mTOR growth signaling pathway was active and that apoptosis was inactive. After the introduction of O-rPRP, the number of follicles and the follicular maturation improved, which was consistent with the improvement of inhibin B levels and subsequent inhibition of FSH. O-rPRP inhibited galactose-induced excessive atresia and provided an overall protective effect on the ovarian follicles. Alternative medicine; Regenerative medicine; Reproductive hormone; Reproductive system; Toxicology; Cell biology; Apoptosis; Galactosemia; mTOR; Ovarian insufficiency; Platelet rich plasma.