Age-related changes in Leydig cell number, daily sperm production, and circulating hormone levels were studied in 15 men between 20 and 48 yr of age and 15 men between 50 and 76 yr of age. Testes and blood samples were obtained at autopsy less than 15 h after death due to trauma or heart attack. Leydig cell number was determined by quantitative histometric estimation of the proportion of glutaraldehyde-perfused, decapsulated testicular parenchyma occupied by Leydig cell nuclei of measured average volume in both testes of each subject. Daily sperm production was determined by phase contrast cytometry of round spermatid nuclei in homogenates of both fixed testes from each individual. LH, FSH, PRL, and testosterone in serum from the heart or large veins were quantified by RIA. No relationship was detected between any of the testicular or hormonal values and postmortem time. The average total number of Leydig cells was reduced by 44% in the older men and was negatively correlated with age (p = -0.62) in all men. Mean serum LH was elevated more than 2-fold in the older men and was positively correlated with age (p = +0.53) in all men. Neither serum testosterone nor serum PRL changed significantly with age. Daily sperm production was more than 50% lower in older men and was negatively correlated with age (p = -0.76) in all men. Serum FSH was more than 3-fold higher in the older men and was positively correlated with age (p = +0.72) in all men. The highest FSH levels were found in men with the lowest rates of sperm production, and FSH and daily sperm production were inversely correlated even after the effects of age were removed. These findings show that the response of the human testis to aging is variable and that the predictive value of age for most testicular characteristics is weak at the level of individual men. Nevertheless, age accounts for more than a third of the variation in Leydig cell number, and it explains more than half the variation in daily sperm production. Hence, age is the largest single contributing factor yet identified in the search for explanations underlying the variation in testicular structure and function found in groups of normal men.

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The human Sertoli cell population was characterized in 14 men by histometric analysis and by direct counts of nuclei in testicular homogenates. Testes obtained at autopsy were perfused with glutaraldehyde and embedded in Epon. Nucleolar and nuclear volumes were determined by the formula of a sphere given the diameter of the nucleoli or average diameter of nuclei measured at the height and width. Nuclear volume was also estimated by adding volumes of nuclear profiles in 0.5-micron serial sections. Sertoli cell number/g was calculated by the product of the percentage nucleoli or nuclei in the parenchyma, parenchymal volume, and histologic correction factor divided by the volume of a single nucleolus or nucleus. Also, Sertoli cell nuclei were counted directly in homogenates of fixed parenchyma. Number of Sertoli cells/g was similar (P greater than 0.05) whether determined by serial sections or in homogenates, but the estimate based on the nucleolar method was higher (P less than 0.01) and the nuclear measurement method was lower (P less than 0.01) than that for serial sections. A group of 37 men aged 20 to 48 yr had significantly (P less than 0.01) more Sertoli cells than did 34 men aged 50 to 85 yr. It is concluded that: 1) the homogenate method is valid for quantification of the Sertoli cell population, 2) Sertoli cells are evenly distributed in different regions of the testis, 3) the average human Sertoli cell supports relatively few germ cells, 4) the human Sertoli cell population declines with age, and 5) there is a significant relationship between sperm production rates and number of Sertoli cells.

Age-related changes in daily sperm production (DSP) and testicular weights were investigated in paired testes from 89 men aged 21-50 years and 43 men aged 51-80 years. For both DSP/testis and DSP/g parenchyma, remarkably large standard deviations exceeded 50% of mean values. However, DSP/g and DSP/testis for both right and left testes were approximately 30% higher in the younger than in the older group (P less than 0.01) and were negatively correlated with age (P less than 0.01) when data from both groups were pooled. Weights of whole testes and of testicular parenchyma were similar in both age groups and were not significantly correlated with age. However, testicular tunic weights were 29% higher in the older group (P less than 0.001) and were positively correlated with age (P less than 0.001). Both testicular tunic weight and the % of total testis occupied by tunic were negatively correlated with DSP/g (P less than 0.01); these correlations were weakened by removing the effect of age. Although total testicular weight and testicular parenchymal weight did not change with age, these values were about 10% lower on the left than on the right (P less than 0.001). In addition to its increase with age, testicular tunic weight was about 8% greater for right than for left testes in all men (P less than 0.001). Although the average size of the testis varied from right to left, DSP/g was similar in paired testes (P = 0.15), and the correlation between right and left DSP/g was high (rho = +0.89, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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Potential daily sperm production per gram of testicular parenchyma (PDSP/g) based on pachytene plus diplotene primary spermatocytes was determined by two methods for 10 men aged 26 to 53 years and compared with published daily sperm production per gram parenchyma (DSP/g) based on round spermatid nuclei for these same men. The PDSP/g based on primary spermatocytes was similar (P greater than 0.05) whether determined by histometric analysis (10.0 +/- 1.1 X 10(6] or from homogenates of parenchyma (10.4 +/- 1.0 X 10(6]. When PDSP/g values were compared to DSP/g (5.9 +/- 0.9 X 10(6) for the histometric or 5.5 +/- 0.8 X 10(6) for the homogenate method), 44.9 +/- 6.7% loss of potential sperm production during postprophase of meiosis was detected by the histometric approach and 48.3 +/- 7.9% loss by the homogenate method. Similar results were obtained when testes of 15 additional men aged 26 to 53 years were evaluated by the homogenate method; PDSP/g was 10.6 +/- 0.6 X 10(6), DSP/g was 5.8 +/- 0.5 X 10(6), and the loss during postprophase of meiosis was 45.3 +/- 4.4%. For all 25 men, DSP/g was significantly (P less than 0.01) correlated with PDSP/g (r = + 0.70) and with the percentage loss of potential sperm production during postprophase of meiosis (r = 0.86). Over 73% of the variation in DSP/g could be attributed to variation in the percentage loss during postprophase of meiosis. Whether faulty meiotic divisions and/or degenerating secondary spermatocytes were responsible, almost half of the potential sperm production in these 25 men was lost during postprophase of meiosis.