Impact of foetal‐onset hypothyroidism on the epididymis of mature rats

Abstract

It is well established that congenital hypothyroidism leads to male infertility. However, there is a dearth of information on foetal-onset hypothyroidism-induced changes in the epididymis. With regard to transient hypothyroidism, the existing literature deals mainly with the testis. However, it is not known whether there is any corresponding alteration in epididymal morphology and physiology under such a condition. The present study is therefore aimed at understanding the impact of persistent and transient hypothyroidism on the concentration of epididymal sex steroids, as they play a vital role in maintaining the normal structure and function of the epididymis. Normal rats of 90 days of age served as controls (Group I). Hypothyroidism was induced by using pregnant/lactating mothers and post-weaning rats to 0.05% (w/v) methimazole (MMI) in the drinking water. Group II were subjected to persistent hypothyroidism from day 9 of post-coitum (pc) to 90 days. Group III rats were subjected to transient hypothyroidism from day 9 day pc to day 1 post-partum (pp), 21 pp or 35 pp (IIIa, b and c, respectively) and group IV rats were given simultaneous T3 supplementation (3 microg/100 g body wt./day i.m.) with MMI from day 9 pc to day 1 pp; 21 pp and 35 pp (Group IVa, b and c). Animals from all groups were killed on day 90 pp. Serum thyroid stimulating hormone (TSH) and thyroid hormones confirmed euthyroidism in group I, IIIa, b and c and IVa, b and c rats and hypothyroidism in group II rats. Caput and cauda epididymal concentration of testosterone, dihydrotestosterone (DHT), estradiol (E2) and androgen binding protein (ABP) markedly decreased in group II rats. While the concentration of testosterone, E2 and ABP increased in group III rats, that of DHT remained unaltered. However, group IV rats maintained normal concentration of the sex steroid and ABP. The activity of 5-alpha-reductase in the epididymis of all the groups followed the same trend as that of the concentration of epididymal DHT. From the present data it is evident that persistent hypothyroidism diminishes the bioavailability of androgens and oestrogens, while transient hypothyroidism enhances the same, indicating the importance of euthyroidism during foetal and neonatal period towards the maintenance of optimal hormonal status in the epididymis required for its maturation.

Mechanism underlying transient gestational-onset hypothyroidism–induced impairment of posttesticular sperm maturation in adult rats

“…Methimazole (MMI, 0.05% in drinking water) was used to induce hypothyroidism (21)(22)(23). The rats were divided into the following groups: group I: control rats at PND 120, not exposed to MMI; group II: MMI treatment to pregnant dams from ED 9 to ED 14, covering the period of fetal testicular differentiation; group III: MMI treatment from ED 9 to ED 18, covering the period of initial differentiation of epididymis from the Wolffian duct; and group IV: MMI treatment from ED 9 to ED 21, covering the entire period of fetal differentiation of the reproductive tract organs.…”

“…Recent studies have shown the presence of specific T 3 receptors in the epididymis of rats (20). Another study from our laboratory (21) emphasized the need for optimum thyroid function during prenatal and postnatal period to have normal androgen status in the epididymis of adult rats.…”

Thyroid hormone receptor α1–β1 expression in epididymal epithelium from euthyroid and hypothyroid rats

“…Direct eVects of TH have also been reported in the rat epididymis, a component of the testicular excurrent duct system, the epididymis is a highly specialized organ involved in the transport, maturation, and storage of spermatozoa (Del Rio et al 2000;Kala et al 2002;St-Pierre et al 2003). The epididymal epithelium contains several cell types: principal, basal, clear, narrow, halo and apical cells.…”

“…Even though direct eVects of TH have been reported in the rat epididymis (Del Rio et al 2000;Kala et al 2002;StPierre et al 2003) as well as in other cells of the male reproductive system, TR localization was only reported for Leydig and Sertoli cells (Hardy et al 1996;. The goals of the present study were: (1) to assess whether epididymal epithelial cells from the diVerent areas of epididymis express TR ( -( isoforms, (2) to depict their subcellular immunolocalization, and (3) to evaluate if the TR expression is modiWed when rats are submitted to hypothyroid state.…”

“…Also, the epididymis can be divided morphologically and functionally into four segments: the initial segment, caput, corpus, and cauda epididymidis (Serre and Robaire 1998;Jones 1998); they exhibit regional diVerences in gene expression (Jervis and Robaire 2001) and diVerential response to androgen withdrawal, aging, and stress indicating that each region represents discrete regulatory units (KirchhoV 1999). Even though most functions of the epididymis depend upon sex steroids (Kala et al 2002), other regulatory molecules are also implicated in the control of epididymal functions. It has been shown that hyperthyroidism diVerentially inXuences epididymal glycosidases that were expected to interfere with sperm maturation and fertilization events (Maran et al 2001).…”