While aging is generally associated with accumulation of DNA damage and decreased cell proliferation, the reason for age-related oligospermia remains unclear. The present study provides evidence that age-related oligospermia may be caused by the altered ability of testicular germ cells to undergo the first mitosis and meiosis. This is due to decreased DNA replication and/or repair in response to DNA damage. Young and aging rats were exposed to either saline or an alkylating agent, cyclophosphamide. The ability of the male germ cells to replicate and/or repair their DNA was estimated by examining expression of PCNA (an essential component of DNA replication and repair machinery) and incorporation of BrdU (analog of thymidine). PCNA expression correlated with that of BrdU incorporation. The ability of germ cells to replicate and/or repair their DNA was affected by both the aging process and cyclophosphamide exposure in a stage-specific manner. At mitosis 1, expression of PCNA and BrdU incorporation decreased with both age and drug exposure. Mitosis 2 was not affected by either age or cyclophosphamide. Meiosis was affected only by the aging process. These differential effects are due, probably, to the different types of DNA damage caused by aging and drug exposure: age produces a long term chronic damage while cyclophosphamide exposure produces an acute short term damage. The results of this study suggest that different mechanisms may be involved in mediating cell cycle arrest and DNA repair at different stages of spermatogenesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20965 |
| Date | January 1999 |
| Creators | Liachenko, Anna. |
| Contributors | Robaire, Bernard (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001652840, proquestno: MQ50820, Theses scanned by UMI/ProQuest. |
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