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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Reproduction

This article is part of the Research TopicCurrent Insights in Sperm Motility and Male FertilityView all articles

Morinda officinalis oligosaccharides improve sperm motility via the gut microbiota and the IGF-1/PI3K/mTOR signaling pathway

Provisionally accepted
Jiajia  HuJiajia Hu1Guoxuan  LiGuoxuan Li2Bingxue  OuyangBingxue Ouyang2Anguo  WangAnguo Wang1Yejun  LiYejun Li1Hui  LuHui Lu1*
  • 1Hainan Women and Children's Medical Center, Haikou, China
  • 2Hainan Medical University, Haikou, China

The final, formatted version of the article will be published soon.

Background: This study aimed to evaluate the efficacy of Morinda officinalis oligosaccharides (MOS) in improving sperm motility and quality in a gossypol-induced asthenozoospermia mouse model, and to explore the potential underlying mechanisms. Methods: Male C57BL/6J mice were randomly assigned to six groups: normal control, model, low-dose MOS (12.5 mg/kg), medium-dose MOS (25 mg/kg), high-dose MOS (50 mg/kg), and positive control (L-carnitine 10 mg/kg). Asthenozoospermia was induced by gossypol (20 mg/kg) injection every 3 days for 30 days, followed by MOS gavage for 14 days. Sperm motility, hormone levels, and histopathological changes were analyzed, and gut microbiota composition was analyzed using 16S rRNA sequencing. Mechanistic validation was performed using Anaerococcus transplantation and rapamycin co-treatment with MOS. Results: Gossypol impaired sperm concentration and motility and induced luminal sperm depletion with vacuolation in the epididymis, without overt structural lesions in the testes, liver, or kidneys. MOS improved sperm motility in a dose-dependent manner, restored testosterone, normalized white blood cells and blood urea nitrogen levels, and reduced sperm morphological abnormalities. High-dose MOS significantly increased microbial α-diversity and enriched Anaerococcus, shifted the microbial community structure toward that of the normal group. MOS and Anaerococcus transplantation activated the IGF-1/PI3K/mTOR pathway, increased Bcl-2, and reduced Cleaved Caspase-3 expression, whereas rapamycin attenuated these improvements, indicating pathway dependence. Conclusions: MOS ameliorate gossypol-induced asthenozoospermia by remodeling the gut microbiota and activating IGF-1/PI3K/mTOR signaling, thereby improving sperm motility and reducing apoptosis. These findings highlight MOS as a promising microbiota-modulating therapeutic strategy for male reproductive dysfunction.

Keywords: Morinda officinalis Oligosaccharides, Asthenozoospermia, Spermmotility, Gut Microbiota, IGF-1/PI3K/mTOR signaling pathway

Received: 23 Sep 2025; Accepted: 08 Dec 2025.

Copyright: © 2025 Hu, Li, Ouyang, Wang, Li and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Hui Lu

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