The essentiality of the epididymal fat pad for spermatogenesis.

In 1935, two landmark publications by Cornell University scientists established the dogma that longevity and reproductive performance in rodents are primarily controlled by energy intake. McCay, Crowell, and Maynard (1) reported that the lifespans of rats maintained on calorie-restricted diets that retarded growth were prolonged, especially in males. In the same year, Asdell and Crowell (2) showed that sexual development in these growth-retarded rats was also retarded; vaginal opening and age at first estrus were delayed, and in contrast to ad libitum-fed rats, the two events became completely dissociated. After World War II, these findings were extended to domestic animals, where it was shown, for example, that calves fed from birth to sexual maturity at 130% of the recommended total digestible nutrient (TDN) allowances first came into estrus at 37.4 wk of age, compared with 49.1 wk for calves fed 100% of recommended TDN allowances and 72.0 wk for calves fed 70% of recommended TDN allowances (3). Similar data were obtained for age at the onset of spermatogenesis in male calves. Greater longevity of dairy cattle fed the 70% recommended TDN allowance was demonstrated by 1964 (4), and later the ability of caloric restriction to increase longevity was demonstrated in species as diverse as flies (5), worms (6), yeast (7), rodents (8), and monkeys (9). Because the calorie-restricted and control diets used in these early studies contained equal amounts of fat, most workers assumed that any influence of fat on reproduction was through its contributions to energy metabolism. However, by 1963, evidence that fat plays an important role in reproductive performance was obtained by Kennedy and Mitra (10) and by Frisch and McArthur in 1974 (11). These studies were the first to indicate that adipose tissue plays a direct role in female reproduction and suggested the need for a minimal amountof fat fornormal reproductivedevelopment.Finally, the discovery of leptin, a peptide hormone produced only in fat cells, removed any doubt as to the ability of fat cells to act as an endocrine organ and firmly established the role of adipose tissue in reproductive performance (12). Now, in what may become another landmark paper, Chu et al. (13) have extended these early results by establishing, for the first time, that a specific fat depot, the epididymal fat pad, produces a locally acting factor responsible for maintaining spermatogenesis in the hamster. Removal of the epididymal fat pad interrupts spermatogenesis and increases FSH concentration but does not affect testosterone, LH concentration, or mating behavior. However, it increases serum FSH concentrations. Transplantation of the excised epididymal fat pad to a sc site did not restore spermatogenesis. Removal of comparable amounts of white adipose tissue from other sites (inguinal) was also without effect, disproving the idea that the effect is due to a decreased energy supply and/or the need for some minimal amount of fat. The authors do point out the possibility that altered testicular blood flow, resulting in increased testicular temperature, might be an alternative explanation for the inhibition of spermatogenesis that occurs after removal of the epididymal fat pad. However, they do not think this is the case, because of the histological normality of the testicular interstitial cells and the normal testosterone production. They also point out that denervation of the testes at both poles, including the pampiniform plexus, which is more likely to produce damage to the venous drainage than epididymal fat pad removal, did not affect spermatogenesis. If the authors are correct in these conclusions, the race is on to identify any compounds of epididymal fat pad