REPRODUCTIVE AGING IN THE MALE BROWN-NORWAY RAT - A MODEL FOR THE HUMAN

Previous studies in the Sprague-Dawley rat have demonstrated that male reproductive aging is primarily a neuroendocrine dysfunction characterized by decreased pulsatile LH secretion leading to low serum testosterone (T) levels, whereas sperm production is relatively well maintained. In contrast to the Sprague-Dawley rat, the Brown-Norway (BN) rat has a longer life span, does not become obese, and experiences fewer age-related tumors of the endocrine or reproductive system, thus providing a disease-free model for studying male reproductive aging. We studied the changes in serum hormone levels and related these alterations to testicular T production, Leydig cell morphometry, and spermatogenesis in young (6 months), aging (22 months), and old (30 months) BN rats. Low serum T levels were associated with decreased LH levels in the 22-month-old (T, 0.58 +/- 0.08 ng/ml; LH, 0.45 +/- 0.06 ng/ml) and 30-month-old rats (T, 0.63 +/- 0.10 ng/ml; LH, 0.34 +/- 0.04 ng/ml) compared to those in young rats (T, 1.35 +/- 0.30 ng/ml; LH, 0.79 +/- 0.10 ng/ml). In vitro Leydig cell T production, basally and after stimulation by LH, was similar in young and old rats. The total testicular T content was lower in 30- than in 6-month-old rats. Testicular morphometry showed smaller Leydig cell volume in the old (857 +/- 97 mum3) than in the young rats (1387 +/- 103 mum3), although their number per testis remained unchanged (6 months, 22.7 +/- 1.6 x 10(6)/testis; 30 months, 25.2 +/- 3.1 X 10(6)/testis). In contrast, a marked (68.4%) reduction in the total number of Sertoli cell per testis was noted in the 30-month-old rats. The proportion of the testis occupied by seminiferous tubules was also reduced in the old rats. Significant (P < 0.05) age-related reductions occurred in tubule diameter, length of tubules, and volume of tubules and their lumens. The testicular sperm concentration and total sperm production were significantly reduced in the 22- and 30-month-old rats. These changes in seminiferous tubule function in the old rats were associated with low serum and testicular inhibin and high serum FSH levels. We conclude that aging in the reproductive axis of the BN rat is manifested by 1) lower serum T levels due to decreased pituitary LH stimulation of endogenous T production, and 2) decreased seminiferous tubule function accompanied by elevated FSH levels indicative of a primary testicular disorder. Because of the coexisting testicular and hypothalamic pituitary dysfunction with aging, the BN rat is a better model to study human male reproductive aging than the Sprague-Dawley rat.