ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Embryonic Development
Developmental and reproductive toxicity assessment of sporoderm-removed Ganoderma lucidum spores
Provisionally accepted
Junxiu Liu1
Yisheng Song1
Chuanhuai Chen1Jing Liu1Siming Zhang1Fang Liu1Ruiyu Tian1
Jinjin Shao1Lili Zhang1Tingli Bian1
Ruimin Sun1
Li Yu1Shuizhen Pan1Yunxiang Chen1Yaoxian Xuan1Hanbo Wang2
Zhenhao Li2Ying Chen1
Lijiang Zhang1*- 1Hangzhou Medical College, Hangzhou, China
- 2Jinhua Shouxiangu Pharmaceutical Co., Ltd., Jinhua, China
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Ganoderma lucidum is a traditional Chinese medicine with high medicinal value and widely used in modern healthcare. Its spores are reported to contain antitumor, anti-inflammatory properties among other biological benefits; however, thick spore-wall limits its bioavailability. Sporoderm-removed G. lucidum spores (RGLS) offer improved bioavailability. However, data on their safety in pregnant and lactating populations remain limited, highlighting the need for developmental and reproductive toxicity (DART) assessment. We aimed to evaluate the developmental and reproductive safety of RGLS to support its clinical application in maternal and perinatal populations. Following ICH S5(R3) guidelines, we conducted three non-clinical DART studies: embryo-fetal developmental toxicity (EFD) in rats, in vitro whole embryo culture (WEC) in rabbits, and prenatal and perinatal toxicity (PPND) in rats. Female rats were administered RGLS (0.4, 1.2, and 4.0 g/kg/day) via oral gavage from gestation day (GD) 6 to GD17 (EFD) or to postnatal day (PND) 20. Rabbit embryos were cultured for 48 h in media containing 0.688, 0.963, and 1.238 mg/mL RGLS extract. Our results showed no maternal toxicity, embryotoxicity, or teratogenicity in rats, apart from reversible drug-mixed feces. Offspring showed no adverse effects on growth, neurodevelopment (Morris water maze), or fertility. Rabbit embryos exhibited normal morphology and organ development. The no observed adverse effect level of RGLS was 4.0 g/kg, which was approximately 20 times the intended clinical dose. Overall, our study supports the safe use of RGLS in clinical applications for pregnant and lactating women, indicating that it can be added to a healthy diet.
Keywords: RGLS, reproductive toxicity, developmental toxicity, NOAEL, medication safety
Received: 15 Sep 2025; Accepted: 05 Dec 2025.
Copyright: © 2025 Liu, Song, Chen, Liu, Zhang, Liu, Tian, Shao, Zhang, Bian, Sun, Yu, Pan, Chen, Xuan, Wang, Li, Chen and Zhang. 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: Lijiang Zhang
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