Reproductive aging in the Brown Norway rat is characterized by acceleratedgerm cell apoptosis and is not altered by luteinizing hormone replacement

Reproductive aging in the male Brown Norway (BN) rat is characterized by de creased Leydig cell steroidogenesis associated with seminiferous tubule dys function. This could be a result of a combination of a primary testicular d efect and a secondary hypothalamic pituitary dysfunction. In the present st udy, we determined in the BN rat whether germ cell loss occurred via apopto sis. We then defined the age of onset of Leydig cell dysfunction and germ c ell loss and examined whether chronic luteinizing hormone (LH) replacement would delay or prevent reproductive aging, Plasma hormone levels, testicula r sperm concentrations, and germ cell apoptosis were studied in 6, 9, 12, 1 5, 18, and 21-month-old BN rats. Beginning at 15 months, testicular weight, sperm concentration, total sperm counts, plasma testosterone, LH, and inhi bin decreased, whereas the proportion of regressed testes and plasma follic le-stimulating hormone (FSH) levels increased with aging, Accelerated germ cell apoptosis involving spermatogonia, preleptotene and pachytene spermato cytes, and spermatids was evident in some tubules of the relatively normal testes from 21-month-old rats. In the regressed testes, complete cessation of spermatogenesis occurred. The apoptotic index was higher in the testes o f old (21-month-old) rats in particular at stages XII-XIV when compared wit h younger animals. Chronic LH replacement (0.5 mu g IP twice per day) admin istered to 15-month-old BN rats for 6 months did not alter plasma hormone l evels, testes weight, sperm concentration or content, or the germ cell apop totic index. In the control group, 3 out of 10 testes were regressed, where as in the LH-replaced group, only 1 out of 12 testes was regressed. We show in this study that early reproductive aging in the BN rat began at around 15 months. Germ cell loss associated with aging occurs via apoptosis. Repla cement therapy with LH for 6 months does not decrease or delay the testicul ar dysfunction associated with aging. It is unlikely that hypothalamic-pitu itary dysregulation is the major cause of testicular aging.