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Updated: Jul 13, 2026
Murine Orchiectomy and Ovariectomy to Reduce Sex Hormone Production
Published on: November 17, 2023
Octylphenol reduces the expressions of steroidogenic enzymes and testosterone production in mouse testis
Suel-Kee Kim1, Jong-Hoon Kim, Ho-Joon Lee
1Laboratory of Toxicogenomics for Endocrine Disruptors and Reproductive Endocrinology, Department of Life Science, Hanyang University, Seoul 133-791, Republic of Korea.
Abstract:
4-tert-octylphenol (OP) is known to disrupt testicular development and reduce male fertility. In the present study, male mice were exposed to OP at two different developmental stages, and the expression of steroidogenic enzymes and testosterone production were evaluated. Juvenile (15-day-old) and adult (8-week-old) male mice were injected with 2, 20, or 200 mg/kg of OP or 0.2 microg/kg of estradiol valerate for 5 days. Testosterone concentration was measured by radioimmunoassay and the expressions of the testicular genes were determined by RT-PCR analysis and immunohistochemistry. In the animals exposed with 20 mg/kg of OP during juvenile stage, histochemical analysis of the testis showed that number of pyknotic germ cells inside the tubule was increased, while the number of oil red O positive Leydig cells was decreased. Moreover, the lumen formation was remarkably delayed. A reduced serum testosterone concentration and down-regulated expressions of the mRNAs for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and 17alpha-hydroxylase/C(17-20) lyase (P450(17alpha)) were also observed after juvenile exposure to OP. Immunohistochemical staining for P450scc was mainly detected in interstitial Leydig cells, and a slightly reduced expression of P450scc protein was observed in the testis exposed to 20 mg/kg of OP during juvenile stage. The present study demonstrates that juvenile exposure to OP inhibits steroidogenesis by decreasing the expressions of steroidogenic enzymes in the testis. Diminished lipid content in Leydig cells and reduced transcriptional expression of the cholesterol transport gene, StAR, also support altered cholesterol metabolism and/or transport as a potential mechanism for the decreased testosterone production following exposure to OP. Altogether, the alteration of steroidogenesis by exposure to OP may adversely affect the normal development of the testis and spermatogenesis.
Insights
Juvenile exposure to 4-tert-octylphenol (OP) impairs male mouse testicular development and testosterone production by inhibiting steroidogenic enzymes and altering cholesterol metabolism. This endocrine disruption affects Leydig cells and germ cells, potentially impacting fertility.
Area of Science:
- Endocrinology
- Toxicology
- Reproductive Biology
Background:
- 4-tert-octylphenol (OP) is an endocrine-disrupting chemical known to affect male reproductive health.
- Testicular development and steroidogenesis are sensitive to environmental exposures during critical developmental windows.
- Understanding the specific mechanisms of OP toxicity on the male reproductive system is crucial for risk assessment.
Purpose of the Study:
- To investigate the effects of juvenile and adult exposure to 4-tert-octylphenol (OP) on testicular development and function in male mice.
- To evaluate the impact of OP on steroidogenic enzyme expression and testosterone production.
- To elucidate potential mechanisms underlying OP-induced reproductive toxicity.
Main Methods:
- Male mice were exposed to varying doses of OP (2, 20, 200 mg/kg) or estradiol valerate during juvenile (15-day-old) or adult (8-week-old) stages for 5 days.
- Testosterone concentrations were measured using radioimmunoassay.
- Gene expression of steroidogenic enzymes (StAR, P450scc, P45017α) was analyzed via RT-PCR and immunohistochemistry; testicular histology was also assessed.
Main Results:
- Juvenile exposure to 20 mg/kg OP significantly increased pyknotic germ cells and decreased Leydig cell lipid content (oil red O staining).
- OP exposure during the juvenile stage led to delayed lumen formation, reduced serum testosterone levels, and down-regulated mRNA expression of StAR, P450scc, and P45017α.
- Reduced P450scc protein expression was observed in testes exposed to OP during the juvenile period.
Conclusions:
- Juvenile exposure to 4-tert-octylphenol (OP) inhibits testicular steroidogenesis by down-regulating steroidogenic enzyme expression.
- Altered cholesterol metabolism and/or transport, indicated by reduced StAR expression and Leydig cell lipid content, contribute to decreased testosterone production.
- OP-induced alterations in steroidogenesis may adversely affect normal testicular development and spermatogenesis, potentially leading to reduced male fertility.
