Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15
Dibutyl phthalate (DBP) has been reported to induce central precocious puberty (CPP). However, the mechanism by which DBP accelerates primordial follicle activation and contributes to CPP has not been studied. This study aims to explore the effects of DBP on puberty onset and the role of primordial...
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Elsevier
2025-07-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325008000 |
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| author | Yangcheng Yao Wenjuan Liu Maoxing Tang Zhaoyi Wang Xiqian Zhang Yufeng Li Xiaomin Xiao Fenghua Liu |
| author_facet | Yangcheng Yao Wenjuan Liu Maoxing Tang Zhaoyi Wang Xiqian Zhang Yufeng Li Xiaomin Xiao Fenghua Liu |
| author_sort | Yangcheng Yao |
| collection | DOAJ |
| description | Dibutyl phthalate (DBP) has been reported to induce central precocious puberty (CPP). However, the mechanism by which DBP accelerates primordial follicle activation and contributes to CPP has not been studied. This study aims to explore the effects of DBP on puberty onset and the role of primordial follicle activation in DBP-related CPP. Female ICR pups (developed by the Institute of Cancer Research, USA) were exposed to DBP from PND5 to PND20. Vaginal opening, a marker of puberty onset, was monitored daily staring from PND20. The involvement of the hypothalamus-pituitary-ovary axis (HPOA) was evaluated, and the activation of primordial follicles was analysed. To investigate the role of primordial follicle activation in CPP development, masitinib was used to establish a model of primordial follicle silencing. Additionally, a neonatal ovary in vitro culture model was developed to explore the mechanism by which DBP accelerates primordial follicle activation. Compared to the control group, the DBP-exposed group exhibited significantly earlier vaginal opening. The hypothalamic gene expression of KISS1, GPR54, as well as serum levels of LH and E2, were elevated. Moreover, the activation of primordial follicle was accelerated in the DBP group. However, these effects were blocked by masitinib treatment. In vitro culture of neonatal ovaries revealed that DBP downregulates AMH expression via the BMP15/p38-MAPK pathway. In conclusion, our study firstly demonstrates that the activation of primordial follicles is essential for CPP development, and DBP contributes to CPP by accelerating primordial follicle activation through the BMP15/p38-MAPK/AMH pathway. |
| format | Article |
| id | doaj-art-72b5017c6d7d47c0becaf3f477d9d2a9 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-72b5017c6d7d47c0becaf3f477d9d2a92025-08-20T03:20:04ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0130011846010.1016/j.ecoenv.2025.118460Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15Yangcheng Yao0Wenjuan Liu1Maoxing Tang2Zhaoyi Wang3Xiqian Zhang4Yufeng Li5Xiaomin Xiao6Fenghua Liu7Department of Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Reproductive Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, China; Correspondence to: No. 521 Xingnan Road Panyu District, Guangzhou, Guangdong Province 511400, China.Dibutyl phthalate (DBP) has been reported to induce central precocious puberty (CPP). However, the mechanism by which DBP accelerates primordial follicle activation and contributes to CPP has not been studied. This study aims to explore the effects of DBP on puberty onset and the role of primordial follicle activation in DBP-related CPP. Female ICR pups (developed by the Institute of Cancer Research, USA) were exposed to DBP from PND5 to PND20. Vaginal opening, a marker of puberty onset, was monitored daily staring from PND20. The involvement of the hypothalamus-pituitary-ovary axis (HPOA) was evaluated, and the activation of primordial follicles was analysed. To investigate the role of primordial follicle activation in CPP development, masitinib was used to establish a model of primordial follicle silencing. Additionally, a neonatal ovary in vitro culture model was developed to explore the mechanism by which DBP accelerates primordial follicle activation. Compared to the control group, the DBP-exposed group exhibited significantly earlier vaginal opening. The hypothalamic gene expression of KISS1, GPR54, as well as serum levels of LH and E2, were elevated. Moreover, the activation of primordial follicle was accelerated in the DBP group. However, these effects were blocked by masitinib treatment. In vitro culture of neonatal ovaries revealed that DBP downregulates AMH expression via the BMP15/p38-MAPK pathway. In conclusion, our study firstly demonstrates that the activation of primordial follicles is essential for CPP development, and DBP contributes to CPP by accelerating primordial follicle activation through the BMP15/p38-MAPK/AMH pathway.http://www.sciencedirect.com/science/article/pii/S0147651325008000Dibutyl phthalateCentral precocious pubertyPrimordial follicleBMP15AMH |
| spellingShingle | Yangcheng Yao Wenjuan Liu Maoxing Tang Zhaoyi Wang Xiqian Zhang Yufeng Li Xiaomin Xiao Fenghua Liu Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15 Ecotoxicology and Environmental Safety Dibutyl phthalate Central precocious puberty Primordial follicle BMP15 AMH |
| title | Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15 |
| title_full | Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15 |
| title_fullStr | Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15 |
| title_full_unstemmed | Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15 |
| title_short | Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15 |
| title_sort | dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating bmp15 |
| topic | Dibutyl phthalate Central precocious puberty Primordial follicle BMP15 AMH |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325008000 |
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