Abstract：
OBJECTIVE: To investigate the specific mechanisms of action of Fertiwell in a mouse model of D-galactose-induced aging of the reproductive system.
METHODS: C57BL/6J mice were randomized into four groups: intact mice (control group), a group of mice with artificial accelerated aging treated with D-galactose alone (Gal), D-galactose followed by Fertiwell (PP), and D-galactose followed by a combination of L-carnitine and acetyl-L-carnitine (LC). The artificial accelerated aging of reproductive system was induced by daily intraperitoneal administration of D-galactose at a dose of 100 mg/kg for 8 weeks. After the end of therapy in all groups, the characteristics of sperm, the level of serum testosterone, immunohistochemical parameters, and the expression of specific proteins were evaluated.
RESULTS: Fertiwell had a pronounced therapeutic effect on testicular tissues and spermatozoa, restored testosterone levels to normal values, and, in addition, was more effective protector against oxidative stress in the reproductive system compared to L-carnitine and acetyl-L-carnitine, which are widely used in male infertility. Fertiwell at a dose of 1 mg/kg allowed to significantly increase the number of motile spermatozoa to 67.4+/-3.1%, which was comparable to indicators in the intact group. The introduction of the Fertiwell positively affected the activity of mitochondria, which was also expressed in an increase in sperm motility. In addition, Fertiwell restored the intracellular level of ROS to the values of the control group and reduced the number of TUNEL+ cells (with fragmented DNA) to the level of intact control. Thus, Fertiwell, containing testis polypeptides, has a complex effect on reproductive function, leading to a change in gene expression, an increase in protein synthesis, the prevention of DNA damage in the testicular tissue, and an increase in mitochondrial activity in testicular tissue and spermatozoa of the vas deferens, which leads to the subsequent improvement of testicular function.
METHODS: C57BL/6J mice were randomized into four groups: intact mice (control group), a group of mice with artificial accelerated aging treated with D-galactose alone (Gal), D-galactose followed by Fertiwell (PP), and D-galactose followed by a combination of L-carnitine and acetyl-L-carnitine (LC). The artificial accelerated aging of reproductive system was induced by daily intraperitoneal administration of D-galactose at a dose of 100 mg/kg for 8 weeks. After the end of therapy in all groups, the characteristics of sperm, the level of serum testosterone, immunohistochemical parameters, and the expression of specific proteins were evaluated.
RESULTS: Fertiwell had a pronounced therapeutic effect on testicular tissues and spermatozoa, restored testosterone levels to normal values, and, in addition, was more effective protector against oxidative stress in the reproductive system compared to L-carnitine and acetyl-L-carnitine, which are widely used in male infertility. Fertiwell at a dose of 1 mg/kg allowed to significantly increase the number of motile spermatozoa to 67.4+/-3.1%, which was comparable to indicators in the intact group. The introduction of the Fertiwell positively affected the activity of mitochondria, which was also expressed in an increase in sperm motility. In addition, Fertiwell restored the intracellular level of ROS to the values of the control group and reduced the number of TUNEL+ cells (with fragmented DNA) to the level of intact control. Thus, Fertiwell, containing testis polypeptides, has a complex effect on reproductive function, leading to a change in gene expression, an increase in protein synthesis, the prevention of DNA damage in the testicular tissue, and an increase in mitochondrial activity in testicular tissue and spermatozoa of the vas deferens, which leads to the subsequent improvement of testicular function.
摘要：
目的：探讨Fertiwell在D-半乳糖诱导的小鼠生殖系统衰老模型中的具体作用机制。
方法：C57BL/6J小鼠随机分为四组：完整小鼠（对照组），一组单独用D-半乳糖（Gal）治疗的人工加速衰老的小鼠，D-半乳糖，然后是Fertiwell（PP），和D-半乳糖,然后是L-肉碱和乙酰基-L-肉碱(LC)的组合。通过每天以100mg/kg的剂量腹腔注射D-半乳糖，持续8周，诱导生殖系统的人工加速衰老。在所有组的治疗结束后，精子的特征，血清睾酮水平,免疫组织化学参数，并评估了特定蛋白质的表达。
结果：费蒂韦尔对睾丸组织和精子有明显的治疗作用，睾酮水平恢复到正常值,and,此外,与L-肉碱和乙酰-L-肉碱相比，对生殖系统中的氧化应激更有效的保护剂，广泛用于男性不育。Fertiwell在1mg/kg的剂量下允许将活动精子的数量显着增加到67.4/-3.1％，与完整组的指标相当。Fertiwell的引入积极影响线粒体的活性，这也表现为精子活力的增加。此外,Fertiwell将ROS的细胞内水平恢复到对照组的值，并将TUNEL细胞（具有片段化的DNA）的数量减少到完整对照的水平。因此，费蒂韦尔,含有睾丸多肽，对生殖功能有复杂的影响，导致基因表达的变化，蛋白质合成的增加，预防睾丸组织中的DNA损伤，睾丸组织和输精管精子的线粒体活性增加，从而导致睾丸功能的后续改善。
方法：C57BL/6J小鼠随机分为四组：完整小鼠（对照组），一组单独用D-半乳糖（Gal）治疗的人工加速衰老的小鼠，D-半乳糖，然后是Fertiwell（PP），和D-半乳糖,然后是L-肉碱和乙酰基-L-肉碱(LC)的组合。通过每天以100mg/kg的剂量腹腔注射D-半乳糖，持续8周，诱导生殖系统的人工加速衰老。在所有组的治疗结束后，精子的特征，血清睾酮水平,免疫组织化学参数，并评估了特定蛋白质的表达。
结果：费蒂韦尔对睾丸组织和精子有明显的治疗作用，睾酮水平恢复到正常值,and,此外,与L-肉碱和乙酰-L-肉碱相比，对生殖系统中的氧化应激更有效的保护剂，广泛用于男性不育。Fertiwell在1mg/kg的剂量下允许将活动精子的数量显着增加到67.4/-3.1％，与完整组的指标相当。Fertiwell的引入积极影响线粒体的活性，这也表现为精子活力的增加。此外,Fertiwell将ROS的细胞内水平恢复到对照组的值，并将TUNEL细胞（具有片段化的DNA）的数量减少到完整对照的水平。因此，费蒂韦尔,含有睾丸多肽，对生殖功能有复杂的影响，导致基因表达的变化，蛋白质合成的增加，预防睾丸组织中的DNA损伤，睾丸组织和输精管精子的线粒体活性增加，从而导致睾丸功能的后续改善。
