Transient fetal/neonatal hypothyroidism affects leydig cell development

TRANSIENT FETAL/NEONATAL HYPOTHYROIDISM AFFECTS LEYDIG CELL DEVELOPMENT Previously the effects of neonatal hypothyroidism have been investigated using rather unphysiological approaches like propyl-thiouracil (PTU) treatment. These studies showed that PTU induced hypothyroidism delayed the development of Sertoli and Leydig cells. In these studies PTU treatment was discontinued before day 28 post partum due to liver and kidney toxicity. Furthermore, it has recently been demonstrated that PTU influences Leydig cell function and possibly development directly, making it difficult to interpret the former hypothyroid data. In the present study a mild form of hypothyroidism was induced already during fetal development. Dams were fed an iodide-free diet to which 0.5% perchlorate was added to deplete endogenous iodide stores. The rats were put on the control diet (iodide content according to the AIN-93 guidelines, 0% perchlorate) 0, 7, 14, 28 or 35 days after parturition. Pups were killed between days 7 and 85 after birth. No differences were found if perchlorate treatment was discontinued at the age of 0 or 7 days. Transient hypothyroidism (14 or 28 days) resulted in a decrease in body and testis weight of the pups, whereas discontinuation of the diet after 35 days resulted in macro-orchidism. In contrast, continued hypothyroidism did not result in absolute macro-orchidism. Leydig cell proliferation, as identified by BrdU and 3ß-HSD labelling, was slightly decreased by transient hypothyroidism (>14d) up to day 21 of age, and significantly increased above control levels from day 35 onwards. Plasma testosterone levels were significantly elevated in the transient hypothyroid groups (>14d) from day 21 post partum onwards. In contrast to the controls, tubular lumen formation was significantly delayed in the testes. The data suggest that (transient) hypothyroidism over an age of 7 days can influence testis maturation. Eddy Rijntjes, Department of Animal Sciences, Human and Animal Physiology Group, Marijkeweg 40, 6709 PG Wageningen, the Netherlands, tel: +31(0)317 482876, email eddy.rijntjes@wur.nl