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Published on: October 13, 2018
Exposure to 4-nonylphenol compromises Leydig cell development in pubertal male mice
Shanhui Tao1, Zhiang Yao1, Huitao Li1
1Department of Pharmacy, Wenzhou University, Wenzhou, Zhejiang 325000, China.
Abstract:
Exposure to 4-nonyl phenol (4-NP) on Leydig cell (LC) development and function remains poorly understood. We explored the effects of 4-NP on LC development and elucidate the underlying mechanisms. Male (28-day-old) mice received orally 4-NP (0.125, 0.25, and 0.5 mg/kg/day) for 28 days. We found that 4-NP at ≥ 0.125 mg/kg markedly compromised serum testosterone levels and LC numbers. Gene and protein expression analysis demonstrated downregulation of key genes and their proteins involved in LC steroidogenesis, including Star, Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b6, and Scarb1. Furthermore, exposure to 4-NP induced oxidative stress, as evidenced by elevated reactive oxygen species (ROS) and malondialdehyde (MDA), as well as reduced superoxide dismutase 1/2 and catalase (CAT). Apoptosis was also observed in LCs following exposure to 4-NP, as shown by an increased BAX/BCL2 ratio and caspase-3. A TM3 mouse LC line further confirmed that 4-NP induced ROS and the expression of apoptosis-related genes and proteins. In conclusion, this study demonstrates that 4-NP exposure compromises LC development through multiple mechanisms.
Insights
4-Nonylphenol (4-NP) exposure harms Leydig cell (LC) development and function. This study reveals 4-NP disrupts testosterone production, induces oxidative stress, and triggers apoptosis in LCs.
Area of Science:
- Endocrinology
- Toxicology
- Reproductive Biology
Background:
- Leydig cells (LCs) are crucial for testosterone production.
- The impact of 4-nonylphenol (4-NP) on LC development and function is not well understood.
- Investigating environmental toxicants like 4-NP is vital for reproductive health.
Purpose of the Study:
- To explore the effects of 4-NP exposure on male mouse Leydig cell development and function.
- To elucidate the underlying molecular mechanisms of 4-NP toxicity in LCs.
Main Methods:
- Adult male mice were orally administered 4-NP at varying doses (0.125, 0.25, 0.5 mg/kg/day) for 28 days.
- Serum testosterone levels, LC numbers, and gene/protein expression related to steroidogenesis were analyzed.
- Oxidative stress markers (ROS, MDA, SOD, CAT) and apoptosis indicators (BAX/BCL2 ratio, caspase-3) were assessed.
- A TM3 mouse LC cell line was used to confirm cellular effects.
Main Results:
- 4-NP exposure significantly reduced serum testosterone levels and LC numbers starting at 0.125 mg/kg.
- Key steroidogenic genes and proteins (e.g., Star, Cyp11a1, Cyp17a1) were downregulated.
- 4-NP induced significant oxidative stress (increased ROS, MDA; decreased SOD, CAT) and apoptosis (increased BAX/BCL2, caspase-3) in LCs.
- In vitro studies using TM3 cells corroborated the in vivo findings regarding ROS and apoptosis.
Conclusions:
- 4-Nonylphenol exposure adversely affects Leydig cell development and function in male mice.
- Mechanisms include disruption of steroidogenesis, induction of oxidative stress, and promotion of apoptosis.
- These findings highlight the potential reproductive risks associated with 4-NP exposure.
