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Effects of lead (Pb) exposure during gestation and lactation on female pubertal development in the rat
Robert K Dearth1, Jill K Hiney, Vinod Srivastava
1Department of Veterinary Anatomy & Public Health, Texas A&M University, College Station, TX 77843-4458, USA.
Insights
Lead exposure during pregnancy or lactation delays female puberty by suppressing key hormones like IGF-1, LH, and estradiol. These detrimental effects occur even at low blood lead levels, highlighting critical developmental risks.
Area of Science:
- Environmental Toxicology
- Reproductive Endocrinology
- Developmental Biology
Background:
- Lead (Pb) exposure is known to delay sexual maturation, but the precise mechanisms and critical exposure windows remain unclear.
- Understanding the impact of low-level lead exposure on reproductive development is crucial for public health.
- Previous research indicates potential disruptions in puberty-related hormones, but detailed insights are lacking.
Purpose of the Study:
- To investigate the effects of gestational and/or lactational lead exposure on the onset of female puberty.
- To determine the relationship between maternal and fetal lead levels and subsequent pubertal hormone changes.
- To elucidate the role of insulin-like growth factor-1 (IGF-1) in lead-induced pubertal delay.
Main Methods:
- Adult female rats were exposed to lead acetate (PbAc) or sodium acetate (control) during gestation and/or lactation.
- Cross-fostering was used to isolate exposure during gestation only, lactation only, or both.
- Blood and tissue lead levels, puberty onset, and serum levels of IGF-1, luteinizing hormone (LH), and estradiol (E2) were measured.
Main Results:
- Lead exposure significantly delayed the onset of puberty in female rats.
- Delayed puberty was associated with suppressed serum levels of IGF-1, LH, and E2.
- Lead exposure did not affect liver IGF-1 mRNA levels, suggesting post-transcriptional regulation of IGF-1.
- Detrimental effects were observed regardless of exposure timing, with gestational exposure showing higher sensitivity.
- Observed effects occurred at blood lead levels lower than previously reported, relevant to human health.
Conclusions:
- Lead exposure disrupts the normal timing of female puberty, likely by interfering with IGF-1 synthesis or secretion.
- The findings suggest that lead's detrimental effects on puberty onset are mediated by suppressed circulating IGF-1, impacting LH release.
- Gestational lead exposure appears particularly sensitive, and effects are seen at environmentally relevant low lead levels.
Abstract:
Lead (Pb) can delay sexual maturation; however, the mechanism and critical time of insult are not clearly defined. Therefore, we assessed maternal Pb levels during low-level gestational and/or lactational exposure, as well as blood and tissue Pb in developing fetuses in relation to the subsequent detrimental effects of Pb on puberty-related hormones and the onset of female puberty. Adult Fisher 344 female rats were gavaged daily with either a 1-ml solution of PbAc containing 12 mg/ml Pb or an equal volume of sodium acetate (NaCl), for the controls, from 30 days prior to breeding until their pups were weaned at 21 days. By cross-fostering at the time of birth, the pups were either exposed to PbAc or NaAc during gestation only, lactation only, or during both gestation and lactation. Pb delayed the timing of puberty and this delay was associated with suppressed serum levels of insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and estradiol (E(2)). Liver IGF-1 mRNA was not affected, suggesting that Pb altered translation and/or secretion of IGF-1. We reported previously that peripherally derived IGF-1 acts at the hypothalamic level to facilitate LH release at puberty; hence, we suggest that the action of Pb in decreasing circulating IGF-1 contributes to the delayed puberty. The detrimental effects occurred regardless of the developmental time of exposure, although gestational exposure appeared more sensitive to the effects of Pb. Also, the effects noted were with blood Pb levels less than previously reported and these levels are relevant to human health concerns.

