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已发表论文
孕龄 SD 大鼠中烯丙雌醇的初步发育安全性评估：F0 代及早期 F1 代终点指标的评价
Authors Jiang L, Zhuan S, Jin W , Wen H, Li D
Received 20 March 2025
Accepted for publication 13 November 2025
Published 26 December 2025 Volume 2025:19 Pages 11659—11673
DOI https://doi.org/10.2147/DDDT.S529390
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Tin Wui Wong
Lai Jiang,1 Shengnan Zhuan,2 Wenjie Jin,3 He Wen,3 Dajin Li4
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Obstetrics and Gynecology, Bengbu Medical University, Bengbu, Anhui, 233030, People’s Republic of China; 3Tianjin Tiancheng New Drug Evaluation Co., Ltd, Tianjin, People’s Republic of China; 4Haboratory of Reproduction Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, 200001, People’s Republic of China
Correspondence: Dajin Li, Email medicallidj@163.com He Wen, Email wenh@tipr.com.cn
Objective: The objective of this study was to evaluate the developmental and hormonal safety profile of different doses of allylestrenol administered during gestation in SD rats, focusing on selected physiological and reproductive indices in the Parental (F0) and First-generation offspring (F1) generations.
Methods: In this study, 138 successfully mated Sprague-Dawley (SD) female rats were randomly divided into solvent control (Sol-C), progesterone injection control (PgI-C), progesterone soft-gel capsule control (PgSC-C), low-dose allylestrenol (Alt-LD, 5 mg kg− 1), medium-dose allylestrenol (Alt-MD, 10 mg kg− 1), and high-dose allylestrenol (Alt-HD, 20 mg kg− 1) groups, with 16 successfully mated female rats in each group. Satellite groups were also established, each consisting of 7 successfully mated female rats.
Results: Estradiol levels on gestation day 19 (GD19) were reduced in the Alt-HD compared to the Sol-C (P < 0.05). Compared with the Sol-C, there was no significant change in the anogenital distance (AGD) on postnatal day 21 (PND21) and PND54 in both male and female littermates in each allylestrenol dose group (P > 0.05). Testosterone levels were significantly elevated in the Alt-MD and Alt-LD groups compared to the Sol-C (P < 0.05). On GD19, the estradiol level was significantly reduced only in the Alt-HD group (9.981 ± 0.514 ng/mL) compared with the Sol-C group (18.725 ± 4.770 ng/mL; P < 0.05). The low-dose (Alt-LD: 17.575 ± 3.017 ng/mL) and medium-dose (Alt-MD: 11.927 ± 3.663 ng/mL) groups showed numerically lower values than Sol-C, but the difference was not statistically significant after adjustment. 95% CIs for Sol-C, Alt-MD, and Alt-HD were [17.1, 20.3], [10.2, 13.7], and [9.4, 10.5] ng/mL, respectively.
Conclusion: Allylestrenol at doses of 5, 10, and 20 mg kg− 1 did not result in overt developmental abnormalities in maternal or offspring rats across selected early endpoints. However, further long-term and functional evaluations across generations are needed to fully establish its safety profile.
Keywords: allylestrenol, SD rats, normal pregnancy, progesterone, reproductive toxicity
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Obstetrics and Gynecology, Bengbu Medical University, Bengbu, Anhui, 233030, People’s Republic of China; 3Tianjin Tiancheng New Drug Evaluation Co., Ltd, Tianjin, People’s Republic of China; 4Haboratory of Reproduction Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, 200001, People’s Republic of China
Correspondence: Dajin Li, Email medicallidj@163.com He Wen, Email wenh@tipr.com.cn
Objective: The objective of this study was to evaluate the developmental and hormonal safety profile of different doses of allylestrenol administered during gestation in SD rats, focusing on selected physiological and reproductive indices in the Parental (F0) and First-generation offspring (F1) generations.
Methods: In this study, 138 successfully mated Sprague-Dawley (SD) female rats were randomly divided into solvent control (Sol-C), progesterone injection control (PgI-C), progesterone soft-gel capsule control (PgSC-C), low-dose allylestrenol (Alt-LD, 5 mg kg− 1), medium-dose allylestrenol (Alt-MD, 10 mg kg− 1), and high-dose allylestrenol (Alt-HD, 20 mg kg− 1) groups, with 16 successfully mated female rats in each group. Satellite groups were also established, each consisting of 7 successfully mated female rats.
Results: Estradiol levels on gestation day 19 (GD19) were reduced in the Alt-HD compared to the Sol-C (P < 0.05). Compared with the Sol-C, there was no significant change in the anogenital distance (AGD) on postnatal day 21 (PND21) and PND54 in both male and female littermates in each allylestrenol dose group (P > 0.05). Testosterone levels were significantly elevated in the Alt-MD and Alt-LD groups compared to the Sol-C (P < 0.05). On GD19, the estradiol level was significantly reduced only in the Alt-HD group (9.981 ± 0.514 ng/mL) compared with the Sol-C group (18.725 ± 4.770 ng/mL; P < 0.05). The low-dose (Alt-LD: 17.575 ± 3.017 ng/mL) and medium-dose (Alt-MD: 11.927 ± 3.663 ng/mL) groups showed numerically lower values than Sol-C, but the difference was not statistically significant after adjustment. 95% CIs for Sol-C, Alt-MD, and Alt-HD were [17.1, 20.3], [10.2, 13.7], and [9.4, 10.5] ng/mL, respectively.
Conclusion: Allylestrenol at doses of 5, 10, and 20 mg kg− 1 did not result in overt developmental abnormalities in maternal or offspring rats across selected early endpoints. However, further long-term and functional evaluations across generations are needed to fully establish its safety profile.
Keywords: allylestrenol, SD rats, normal pregnancy, progesterone, reproductive toxicity