[Gly14]-humanin exerts a protective effect against D-galactose-induced primary ovarian insufficiency in mice

• Published in: Reproductive biomedicine online Vol. 48; no. 2; p. 103330
• Main Authors: Huang, Jin, Feng, Qiwen, Zou, Liping, Liu, Yumeng, Bao, Meng, Xia, Wei, Zhu, Changhong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2024
• Subjects: Animals; Antioxidants - pharmacology; autophagy; Female; Galactose - adverse effects; humanin; Humans; Intracellular Signaling Peptides and Proteins; Mice; oxidative stress; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - prevention & control; primary ovarian insufficiency, D-galactose; autophagy; primary ovarian insufficiency, D-galactose; humanin; oxidative stress
• ISSN: 1472-6483; 1472-6491
• DOI: 10.1016/j.rbmo.2023.103330

Is there a protective effect of the humanin derivative [Gly14]-humanin (HNG) on a D-gal-induced mouse model of primary ovarian insufficiency (POI), and what is the underlying mechanism? D-gal (200 mg/kg/day) was injected subcutaneously for 6 weeks to induce the mouse POI model. Mice treated with HNG were injected intraperitoneally with different concentrations for 6 weeks. Ovarian morphology, function, levels of sex hormones and states of oxidative stress in the ovary and body were evaluated. Compared with the D-gal group, 10 mg/kg HNG improved the abnormal ovarian morphology and oestrous cycle (P = 0.0036), increased the number of ovarian follicles (P = 0.0016) and litters (P = 0.0127), and increased the levels of oestrogen (P = 0.0043) and AMH (P = 0.0147). Antioxidant indicators in the ovaries and serum of mice, including total antioxidant capacity (P = 0.0004 and P = 0.0032, respectively), catalase (P = 0.0173 and P = 0.0103, respectively) and glutathione (both P < 0.0001) were significantly increased. The oxidation indicator malondialdehyde decreased significantly (all P < 0.01). Apoptosis of ovarian granulosa cells was significantly reduced (P = 0.0140) as was the expression of senescence-related proteins p53, p21 and p16 (all P < 0.01). The level of autophagy in ovarian tissue of mice treated with high increased (significantly increased LC3 protein [P < 0.0001] and significantly reduced p62 protein [P = 0.0007]). HNG inhibited D-gal-induced oxidative stress, apoptosis and ovarian damage, promoting ovarian autophagy. HNG may be a potential prophylactic agent against POI. [Display omitted]