Influence of hypothyroidism on testicular mitochondrial oxidative stress by activating the p38 mitogen-activated protein kinase and c-Jun NH₂-terminal kinase signaling pathways in rats

Abstract

<jats:p> Thyroid hormone deficiency can impair testicular function. However, knowledge of the effects of mitogen-activated protein kinase (MAPK) pathways on testicular mitochondrial oxidative damage induced by hypothyroidism is still rudimentary. This study aims to explore the possible mechanisms of testicular mitochondrial oxidative damage in hypothyroidism rats. Wistar male rats were randomly divided into control (C), low- (L), and high-hypothyroidism (H) groups (1 ml/100 g body weights (BWs)/day 0, 0.001% and 0.1% propylthiouracil, respectively) by intragastric gavage for 60 days. Blood samples were collected to measure the levels of serum triiodothyronine (T<jats:sub>3</jats:sub>), thyroxine (T<jats:sub>4</jats:sub>), and thyroid stimulating hormone (TSH). Testicular mitochondrial homogenates were used to measure the activities of superoxide dismutase (SOD), catalase (CAT), and Ca<jats:sup>2+</jats:sup>-ATPase as well as protein and mRNA expression of androgen receptor (AR), p38 MAPK, and c-Jun NH<jats:sub>2</jats:sub>-terminal kinase (JNK). Results showed that the BWs, testes weights, and levels of T<jats:sub>3</jats:sub> and T<jats:sub>4</jats:sub> were all significantly decreased and the testes coefficient and level of TSH were significantly increased in the H group. There were significant decreases in SOD activity in the H group as well as decreases in CAT and Ca<jats:sup>2+</jats:sup>-ATPase activities in the L and H groups. Additionally, protein expression of AR decreased significantly and protein expression of phosphorylated p38MAPK and JNK increased significantly in the H group. Therefore, the study suggests that hypothyroidism could affect male reproductive function by disturbing expression of AR, changing the activity of Ca<jats:sup>2+</jats:sup>-ATPase, inducing oxidative stress and then leading to activation of p38MAPK and JNK signaling in the testicular mitochondria. </jats:p>

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats

“…As for hormone receptors and membrane transporters, hypothyroidism increased Ar expression in the testes. Similar to the present study, Chang et al 49 observed an increase in testicular Ar mRNA in hypothyroid rats but a reduction in the AR protein levels. This suggests that there are post-transcriptional alterations in testicular AR expression in hypothyroid rats 49 .…”

“…Similar to the present study, Chang et al 49 observed an increase in testicular Ar mRNA in hypothyroid rats but a reduction in the AR protein levels. This suggests that there are post-transcriptional alterations in testicular AR expression in hypothyroid rats 49 . Furthermore, the increase in Ar mRNA observed in hypo rats may be the result of the reduction in plasma testosterone, because androgens negatively regulat e Ar gene expression 50 , 51 .…”

Chlorella vulgaris or Spirulina platensis mitigate lead acetate-induced testicular oxidative stress and apoptosis with regard to androgen receptor expression in rats

“…These resulting in steroidogenesis inhibition in Leydig cells whereby TNF-α lessened testicular 3band 17b-17ß-hydroxysteroid dehydrogenase activity resulting in reduced testosterone level (Hales 2002;Hong et al 2004). Consequently, AR damage are occurred in response to testicular oxidative burden (Chang et al 2019;Yao et al 2007).…”

Omega 3 fatty acids preserve testicular function by ameliorating BPF-induced dysthyroidism: role of p53/Bcl-2 signaling and proton pump activities

“…Hence, testicular cells are equipped with the transporters and enzymes required to maintain thyroid hormone homeostasis within the testes (Gao et al, 2014). Physiologically, TH is an important factor in redox balance, and alteration in thyroid homeostasis can lead to oxidative stress, apoptosis, and proton pump dysfunction (Chang et al, 2019). Hypothyroidism has been shown to disrupt proton pump (such as Ca2+-ATPase) activities, which in turn disrupts calcium homeostasis (Chang et al, 2019).…”

“…Physiologically, TH is an important factor in redox balance, and alteration in thyroid homeostasis can lead to oxidative stress, apoptosis, and proton pump dysfunction (Chang et al, 2019). Hypothyroidism has been shown to disrupt proton pump (such as Ca2+-ATPase) activities, which in turn disrupts calcium homeostasis (Chang et al, 2019). Maintaining intracellular calcium is important for mitochondrial function since calcium imbalance is a major trigger for mitochondrial dysfunction associated with oxidative stress and apoptosis (Nazıroğlu et al, 2012).…”