New insights for male infertility revealed by alterations in spermatic function and differential testicular expression of thyroid-related genes

Abstract

The impact of thyroid hormone (TH) disorders on male reproductive biology has been a controversial issue for many years. Recently, we reported that hypothyroid male rats have a disruption of the seminiferous epithelium, which may compromise spermatogenesis. To improve the understanding of the reproductive pathogenesis of hypothyroidism and hyperthyroidism, male Wistar rats that developed these dysfunctions in adulthood were used as an experimental model. We evaluated the sperm production, reserves, transit time, morphology, and functionality (acrosome integrity, plasma membrane integrity, and mitochondrial activity), and the testicular expression of the TH receptors (Thra1 and Thra2, Thrb1, and Thrb2), deiodinases (Dio2 and Dio3), and the Mct8 transporter (Slc16a2) were assessed by reverse transcription followed by real-time quantitative PCR (RT-qPCR). The results were evaluated statistically by ANOVA and Tukey HSD test (P < 0.05). Hypothyroidism decreased the total and daily sperm productions and increased the sperm transit time through the epididymis, while the sperm functionality was reduced in both thyroid dysfunctions. Regarding the modulation of gene expression in the testis, hypothyroidism increased the expression of Thra1 and decreased the expression of Dio3, and hyperthyroidism increased the expression of Slc16a2. The observed alterations in spermatic production and function and in the expression of the TH receptor, deiodinase, and the TH transporter are suggestive of TH participation in spermatogenesis in adulthood.

Paternal Subclinical Hypothyroidism Affects the Clinical Outcomes ofIn VitroFertilization/Intracytoplasmic Sperm Injection

“…Others have reported on the negative effects of hypothyroidism on male reproductive function (7,26), and particularly on sperm concentration, motility, and morphology (27,28). Similar observations have been made in animal models (29). Very few studies, however, have focused on the effects of SCH on male reproduction.…”

“…As only a few studies have delineated the mechanistic links between thyroid dysfunction and spermatogenesis, we put forward the following proposals that might help explain the issues. First, animal studies have indicated that a hypothyroid state can affect sperm function (29). An increase in reactive oxygen species production was also observed in sperm isolated from hypothyroid animal models (33).…”

Thyroid Hormones and Spermatozoa: In Vitro Effects on Sperm Mitochondria, Viability and DNA Integrity

“…It is known that the thyroid hormones (THs), 3,5,3′-triiodothyronine (T 3 ) and thyroxine (T 4 ) impact the reproductive function, and thyroid dysfunction is associated with an adverse effect on fertility, both in men [1,2] and women [3]. Indeed, hyperthyroidism or thyrotoxicosis damages spermatogenesis causing maturation arrest, impairs mitochondrial activity and alters the antioxidant systems in rats [4]. Hyperthyroidism results in asthenozoospermia in humans [5,6,7].…”

Altered sperm parameters and subclinical hypothyroidism; A cross sectional study in Karachi, Pakistan

“…5 It reduces serum testosterone levels and is associated with hypogonadism and sperm morphological abnormalities. 4,7 More recent studies, however, have shown that hypothyroidism causes decreased total testosterone (TT) and "sex hormone binding globulin (SHBG)" levels, whereas "luteinizing hormone (LH)"…”