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Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate
B T Akingbemi1, R T Youker, C M Sottas
1Center for Biomedical Research, Population Council, New York, New York 10021, USA. benson@popcbr.rockefeller.edu
Biology of Reproduction
|September 22, 2001
Summary
Di(2-ethylhexyl)phthalate (DEHP) exposure in rodents impacts male reproductive health by altering testosterone (T) and luteinizing hormone (LH) levels. These effects depend on the developmental stage during exposure, influencing Leydig cell function and T biosynthesis.
Area of Science:
- Endocrinology
- Reproductive Toxicology
- Environmental Health
Background:
- Phthalates, including di(2-ethylhexyl)phthalate (DEHP), are environmental contaminants linked to reproductive anomalies in rodents.
- Concerns exist regarding the potential adverse effects of phthalates on human reproductive health.
- Testosterone (T), crucial for male fertility, is produced by testicular Leydig cells and regulated by luteinizing hormone (LH).
Purpose of the Study:
- To investigate the impact of DEHP exposure on Leydig cell androgen biosynthesis in developing and adult rats.
- To determine the effects of DEHP on serum T and LH levels at different developmental stages.
- To identify the no-observed-effect-level (NOEL) and lowest-observed-effect-level (LOEL) for DEHP exposure.
Main Methods:
- Pregnant rats were administered DEHP during gestation; offspring were assessed for serum T and LH levels at various ages.
- Prepubertal and adult rats were gavaged with varying doses of DEHP for 14 or 28 days.
- Leydig cell steroidogenesis, including enzyme activity and T production, was evaluated.
- Serum T and LH levels were measured in exposed rats.
Main Results:
- Gestational DEHP exposure reduced serum T and LH in male offspring at early ages (21 and 35 days), with effects diminishing by 90 days.
- In prepubertal rats, DEHP exposure decreased steroidogenic enzyme activity (e.g., 17beta-hydroxysteroid dehydrogenase) and T production.
- Extended prepubertal exposure paradoxically increased T production capacity and serum LH.
- Adult rat exposure to DEHP did not alter androgen biosynthesis.
- NOEL and LOEL were determined to be 1 mg/kg/day and 10 mg/kg/day, respectively.
Conclusions:
- DEHP's effects on Leydig cell steroidogenesis are critically dependent on the developmental stage at the time of exposure.
- DEHP may disrupt male reproductive health by modulating T-biosynthetic enzyme activity and serum LH levels.
- These findings highlight the importance of developmental timing in assessing the risks of environmental endocrine disruptors.