Regular Article
Reproductive Toxicity and Growth Effects in Rats Exposed to Lead at Different Periods during Development

https://doi.org/10.1006/taap.1996.0044Get rights and content

Abstract

The reproductive toxicity and growth effects of developmental lead exposure were assessed using a rat model in which 0.6% (w/v) lead acetate was administered in the drinking waterad libitum.Three series of experiments were conducted in which lead exposure was initiated beginningin utero,prepubertally, or postpubertally. Lead effects were measured on reproductive physiology and endocrinology, sexually dimorphic hepatic testosterone hydroxylation, and growth rates in both male and female animals. In male animals secondary sex organ weights were significantly decreased only in animals exposed prepubertally. In addition, serum testosterone levels were significantly suppressed, most severely in animals exposed fromin utero(in thein uterogroup). Little effect was observed in adult female rats. However, in female animals exposed prepubertally, delayed vaginal opening and disrupted estrus cycling was observed. More severe reproductive disruption was accompanied by suppression of circulating estradiol in thein uterogroup. Effects on circulating sex steroids were accompanied by variable effects on circulating luteinizing hormone (LH) levels, pituitary LH, and pituitary LHβ mRNA, suggesting a dual site of lead action: (a) at the level of the hypothalamic pituitary unit, and (b) directly at the level of gonadal steroid biosynthesis. Prepubertal growth in both sexes was suppressed 25% in thein uterogroup. However, pubertal growth rates were significantly suppressed only in male animals and postpubertal growth was not significantly different from controls in any of the experiments, despite continued exposure to high lead levels in the drinking water. In addition, at age 85 days, male-specific hepatic hydroxylation of testosterone at positions 2α and 16α, which is catalyzed by a cytochrome P450 isozyme CYP 2C11, itself regulated by sexually dimorphic growth hormone secretion, was unaffected. This suggests that the growth effects of lead are possibly due to a delay in the development of sex-specific pituitary growth hormone secretion patterns rather than a persistent developmental defect. Thus, the reproductive and growth effects of lead are complex and sex-dependent, and appear to involve multiple sites on the hypothalamic–pituitary–gonadal axis.

References (0)

Cited by (138)

  • Sodium para-aminosalicylic acid ameliorates brain neuroinflammation and behavioral deficits in juvenile lead-exposed rats by modulating MAPK signaling pathway and alpha-synuclein

    2023, Toxicology Letters
    Citation Excerpt :

    The reasons may be due PAS’s short t1/2 (34 min) in plasma, thus, only high doses of PAS might be able maintain a stable concentration of PAS in the blood and allow sufficient levels PAS and its major metabolite AcPAS to cross the BBB into the brain parenchyma (Hong et al., 2011). Numerous studies have shown that early-life Pb exposure has negative effect on the growth development (Ronis et al., 1996; Liu et al., 2019). In the present study, we found that the body-weight gain of Pb-exposed rats was significantly slower than that in the control group, suggesting that Pb exposure during juvenile period delayed growth development.

  • Effects of metallic elements on reproduction and development

    2021, Handbook on the Toxicology of Metals: Fifth Edition
  • Endocrine-disrupting chemical removal by carbon nanocomposites

    2021, Handbook of Advanced Approaches Towards Pollution Prevention and Control
  • Effects of metallic elements on reproduction and development

    2021, Handbook on the Toxicology of Metals: Volume I: General Considerations
View all citing articles on Scopus
View full text