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

ObjectiveTo understand the mechanism underlying gestational-onset hypothyroidism–induced male infertility.DesignControlled laboratory study.SettingResearch laboratory in a university department of endocrinology.Animal(s)Wistar rat.Intervention(s)Pregnant rats were exposed to methimazole from embryonic days 9 to 14, 18, and 21, covering specific fetal periods of differentiation and development of male reproductive tract organs.Main Outcome Measure(s)Fertility of male rats was assessed by testing sperm count, forward motility, and in vivo fertilizing ability. Secretory activity of the epididymis was evaluated by quantifying sialic acid, carnitine, and glycerylphosphorylcholine. Bioavailability of androgens was assessed by quantifying testosterone in serum and testicular interstitial fluid and epididymal 5α-reductase activity/mRNA expression. Androgen receptor (AR) status in the epididymis was tested by detecting the expression levels of its mRNA and protein, as well as ligand binding activity. Data were analyzed statistically by one-way analysis of variance.Result(s)Gestational exposure to methimazole decreased sperm forward motility, in vivo fertilizing ability, bioavailability of androgens, AR status, and secretory activity of the epididymis in adult rats.Conclusion(s)Transient gestational-onset hypothyroidism affects male fertility by impairing posttesticular sperm maturation process in the epididymis, owing to subnormal androgen(s) bioavailability, AR expression, and AR functional activity.