Journal
TOXICOLOGY
Volume 210, Issue 2-3, Pages 247-256Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2005.02.004
Keywords
lead; neonatal periods; male reproductive dysfunction; defective sperm function; macrophages
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Funding
- NIEHS NIH HHS [T32ES07251] Funding Source: Medline
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BALB/c mice were exposed to 0.1 ppm lead acetate in the drinking water from postnatal day (PND) I for 6 weeks. Until PND21, lead exposure was from mother's milk; thereafter, it was directly from the drinking water. The blood lead levels were the highest in pups before weaning (59.5 +/- 0.9 mug/dL) and significantly lower between PND21 and PND42 (20.3 +/- 4.7 mug/dL). At PND42, lead-exposed male mice were tested for fertility, sperm DNA, and macrophage number. Mating of lead-treated mates with non-treated females confirmed the reduction of fertility in the exposed males. Flow cytometric studies of testicular preparations indicated that the sperm count was not different between lead-exposed and control males however, the lead-treated mice had a significant increase in the number of testicular cells having a <1n amount of DNA, which coincided with a decrease in the number of testicular cells with a 2n and 4n amount of DNA. The number of testicular macrophages also was decreased in lead-exposed males, which could reflect altered levels of CSF-1 or response to CSF-1, as previously reported [Kowolenko, M., Tracy, L., Lawrence, D.A., 1989. Lead-induced alterations of in vitro bone marrow cell responses to colony stimulating factor- 1. J. Leukoc. Biol. 45, 198-206]. Our study showed that exposure to 0.1 ppm of lead during the neonatal and adolescent period is sufficient to reduce fertility in adult male mice; however, it did not affect sperm count on PND42. The presence of an increased number of apoptotic (<1n amount of DNA) testicular cells may be diagnostic of defective sperm function. Thus, an administered dose of 0.1 ppm via drinking water ingestion by neonatal male BALB/c mice sufficient to produce PbB of 20-60 mg/dL compromised reproductive function in these mice as adults. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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