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Dietary-Induced Hyperthyroidism Marginally Affects Neonatal Testicular Development

DIRK G. DE ROOIJ

From the ^* Department of Animal Sciences, Human & Animal Physiology Group, Wageningen University, Wageningen, The Netherlands; and the Department of Endocrinology and Metabolism, Utrecht University, Utrecht, The Netherlands, and the Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands.

Correspondence to: Dr Katja J. Teerds, Department of Animal Sciences, Human & Animal Physiology Group, Wageningen University, Marijkeweg 40, 6709 PG Wageningen, The Netherlands (e-mail: katja.teerds{at}wur.nl).

The objective of this study was to determine whether dietary-induced mild fetal/neonatal hyperthyroidism influenced the initiation of spermatogenesis and the development of the adult-type Leydig cell population. Previously, the effects of neonatally induced hyperthyroidism have been investigated in rats using rather high doses (5 to 10 µg/100 g body weight) of tri-iodothyronine, which not only influenced testicular development, but also negatively affected the general body condition of the animals. To induce hyperthyroidism the diet of the dams was supplemented with 15 µg thyroxine (T₄)/100 g body weight 2 weeks prior to mating and the dams and their offspring were kept on this diet until sacrifice. Pups were killed between days 7 and 64 after birth. At the age of 12 days plasma thyroid-stimulating hormone (TSH) levels tended to be lower in hyperthyroid pups, and from the age of 15 days onwards plasma TSH levels were significantly lower in hyperthyroid animals. Concomitantly, plasma T₄ levels were significantly elevated. From the age of 12 days onwards, plasma follicle-stimulating hormone levels were lower in hyperthyroid animals compared with age-matched control groups. Sertoli cell differentiation did not seem to be influenced by the mild hyperthyroid condition, as no difference in tubule lumen formation was observed between euthyroid and hyperthyroid animals. Nevertheless, a small effect on the progression of spermatogenesis was observed 15 days after birth, as the most advanced type of germ cells in the control testis were pachytene spermatocytes, whereas in the hyperthyroid testis these were leptotene and zygotene spermatocytes. Leydig cell proliferation was decreased in the hyperthyroid pups at the age of 15 days and slightly elevated at later ages, suggesting a possible slower onset of the proliferative activity of these cells than in the euthyroid control animals. Taken together, the present results suggest that even mild dietary-induced hyperthyroidism transiently affects the development of the adult-type Leydig cell population as well as the initial progression of spermatogenesis.

     Key words: Thyroxine, Leydig cell development, Sertoli cell differentiation, hyperthyroid