Adult testicular enlargement induced by neonatal hypothyroidism is accompanied by increased sertoliand germ cell numbers

Our previous studies have shown that transient neonatal hypothyroidism, induced by treatment with the reversible goitrogen 6-propyl-2-thiouracil (PTU), increases testicular size and daily sperm production in the adult rat by up to 82% and 136%, respectively. The objective ofthe present study was to examine morphological and functional changesin adult seminiferous tubules associated with PTU-induced increasesin testicular size and sperm production. Sprague-Dawley rats weretreated with PTU from birth to day 25 or left untreated; for morphometry, all testes were fixed by vascular perfusion at 90 days of age.Although testicular weight was increased 62% in treated rats, grosspathological changes were not evident in these organs, and spermatogenesis appeared morphologically normal. The percent area of testisoccupied by seminiferous tubules was equal in control and treatedtestes, but mean seminiferous tubule diameter and length were increased in the PTU-treated testis. The adult number of Sertoli cells in treated testes was increased by 157%, and the numbers of leptotene spermatocytes and round spermatids were increased 84% and 93%, respectively. These results demonstrate that increases in Sertoli cellnumbers result in increased sperm production and support the ideathat Sertoli cells are the major regulators of the magnitude of spermproduction. Although the round spermatid to Sertoli cell ratio wasreduced by nearly 30%, the number of round spermatids per g testiswas increased by 14%. This increased efficiency of sperm productionwas accomplished by an increased density of Sertoli cells along thebasement membrane and an increased height of the seminiferousepithelium. Despite the large increase in Sertoli cell numbers in treatedrats, Northern blot analysis using Sertoli cell-specific cDNA probes fortransferrin and androgen-binding protein indicated that relative steadystate levels of mRNAs per Sertoli cell for these two secretory proteinswere similar in control and treated rats at 90 days of age.