Liu Shuang, Wang Weiyong, Liu Huiyu, Wei Hongwei, Weng Yashuang, Zhou Wenjun, Zhang Xiaodan, He Sihui, Chen Ye, Wang Yahong, Zhang Meijia, Chen Xin
The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Reproductive Medicine Center, Shunde Hospital of Southern Medical University (The First People's Hospital of Shunde), Foshan, 528300, China.
Mol Med. 2024 Dec 20;30(1):251. doi: 10.1186/s10020-024-01042-z.
Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear.
The role of BBR on primordial activation was investigated by neonatal mouse ovary culture and intraperitoneal injection, and by human ovarian fragment culture. Furthermore, the effect of BBR on the quantity of ovulated oocytes was investigated by the intragastric administration of aged mice.
BBR in vitro culture and in vivo intraperitoneal injection significantly increased growing follicle number and phosphorylated protein kinase B (p-Akt) levels in neonatal mouse ovaries. BBR also significantly increased the relative fluorescence intensities of p-Akt in the oocytes of primordial follicles. BBR-increased the number of growing follicles and the levels of p-Akt were blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Furthermore, BBR intragastric administration significantly increased the quantity of ovulated oocytes in aged mice. Moreover, BBR significantly increased growing follicle proportion and p-Akt levels in cultured human ovarian fragments.
BBR promotes mouse and human primordial follicle activation through the PI3K/Akt pathway in oocytes, and improves the quantity of ovulated oocytes in aged mice. Our results suggest a potential use of oral medicine BBR to improve fertility in POI patients and aged women.
原始卵泡激活对于高龄女性和卵巢早衰（POI）女性的生殖至关重要。但目前缺乏有效且安全的体内激活原始卵泡的治疗方法。黄连素（BBR）具有多种药理特性，但其对原始卵泡激活的影响尚不清楚。
通过新生小鼠卵巢培养和腹腔注射以及人卵巢组织块培养来研究BBR对原始卵泡激活的作用。此外，通过对老龄小鼠灌胃给药来研究BBR对排卵卵母细胞数量的影响。
BBR体外培养和体内腹腔注射显著增加了新生小鼠卵巢中生长卵泡的数量以及磷酸化蛋白激酶B（p-Akt）的水平。BBR还显著增加了原始卵泡卵母细胞中p-Akt的相对荧光强度。BBR增加生长卵泡数量以及p-Akt水平的作用被磷脂酰肌醇3激酶（PI3K）抑制剂LY294002阻断。此外，BBR灌胃给药显著增加了老龄小鼠排卵卵母细胞的数量。而且，BBR显著增加了培养的人卵巢组织块中生长卵泡的比例和p-Akt水平。
BBR通过卵母细胞中的PI3K/Akt途径促进小鼠和人原始卵泡激活，并改善老龄小鼠排卵卵母细胞的数量。我们的结果提示口服药物BBR在改善POI患者和高龄女性生育能力方面具有潜在用途。
