Transient Hypothyroidism: Dual Effect on Adult-Type Leydig Cell and Sertoli Cell Development.

Eddy Rijntjes,Katja J Teerds,Marcos L M Gomes,Hans J M Swarts,Jaap Keijer,Nina Zupanič

doi:10.3389/fphys.2017.00323

Eddy Rijntjes, Katja J Teerds + Show 4 more

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https://doi.org/10.3389/fphys.2017.00323

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Abstract

Transient neonatal 6-propyl-2-thiouracil (PTU) induced hypothyroidism affects Leydig and Sertoli cell numbers in the developing testis, resulting in increased adult testis size. The hypothyroid condition was thought to be responsible, an assumption questioned by studies showing that uninterrupted fetal/postnatal hypothyroidism did not affect adult testis size. Here, we investigated effects of transient hypothyroidism on Leydig and Sertoli cell development, employing a perinatal iodide-deficient diet in combination with sodium perchlorate. This hypothyroidism inducing diet was continued until days 1, 7, 14, or 28 postpartum (pp) respectively, when the rats were switched to a euthyroid diet and followed up to adulthood. Continuous euthyroid and hypothyroid, and neonatal PTU-treated rats switched to the euthyroid diet at 28 days pp, were included for comparison. No effects on formation of the adult-type Leydig cell population or on Sertoli cell proliferation and differentiation were observed when the diet switched at/or before day 14 pp. However, when the diet was discontinued at day 28 pp, Leydig cell development was delayed similarly to what was observed in chronic hypothyroid rats. Surprisingly, Sertoli cell proliferation was 6- to 8-fold increased 2 days after the diet switch and remained elevated the next days. In adulthood, Sertoli cell number per seminiferous tubule cross-section and consequently testis weight was increased in this group. These observations implicate that increased adult testis size in transiently hypothyroid rats is not caused by the hypothyroid condition per se, but originates from augmented Sertoli cell proliferation as a consequence of rapid normalization of thyroid hormone concentrations.

Highlights

It is generally accepted that postnatal development of the testis is highly dependent on the coordinated growth and differentiation of both somatic (Leydig and Sertoli) cells and germ cells (Picut et al, 2015)
Detailed data on these variables from day 12 to 21 pp is provided in Supplementary Table 2
Except for the T28 rats on day 100 pp, when there was no difference, the body weights of the hypothyroid, T28 and PTU pups were significantly lower at all ages when compared to the respective age-matched euthyroid controls

Summary

Introduction

It is generally accepted that postnatal development of the testis is highly dependent on the coordinated growth and differentiation of both somatic (Leydig and Sertoli) cells and germ cells (Picut et al, 2015). It was reported that under PTU-induced hypothyroid conditions, adult-type Leydig cell progenitor formation was arrested in rats up to 21 days after birth (Mendis-Handagama et al, 1998). Following cessation of the hypothyroid condition at the age of 26 days, developing Leydig progenitor cells start to proliferate massively (Hardy et al, 1996), leading to an ∼70% increase in the adult-type Leydig cell population in adulthood as compared to the euthyroid controls (Cooke et al, 1991; Hardy et al, 1993). Hypothyroidism has been reported to prolong the phase of Sertoli cell proliferation, leading to an augmented testicular Sertoli cell number (van Haaster et al, 1992)

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