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| REVIEW ARTICLE |
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| Year : 2019 | Volume
: 8
| Issue : 5 | Page : 203-210 |
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Thyroid hormones in male reproduction and infertility
Ahmed Alahmar MBChB, MSc. 1, Sulagna Dutta2, Pallav Sengupta3
1 College of Science, University of Sumer, Iraq
2 Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Malaysia
3 Department of Physiology, Faculty of Medicine and Biomedical Sciences, MAHSA University, Malaysia
| Date of Submission | 24-May-2019 |
| Date of Decision | 20-Jun-2019 |
| Date of Acceptance | 19-Jul-2019 |
| Date of Web Publication | 07-Sep-2019 |
Correspondence Address:
Ahmed Alahmar
College of Science, University of Sumer
Iraq
 Source of Support: None, Conflict of Interest: None  | 10 |
DOI: 10.4103/2305-0500.268135
Thyroid hormones have been well studied for its relevance to male reproduction in the last few decades. They are considered as essential regulators of male reproductive functions and play vital roles in male gonadal developments. Hyperthyroidism and hypothyroidism both affect testicular functions and influence neuroendocrine regulations over reproductive functions via the crosstalk between the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis. The alterations in the male reproductive hormonal milieu by thyroid hormones may lead to reduced testosterone levels and deterioration of semen quality. However, there are very few reports on the direct effects of thyroid disorders upon testicular functions and semen quality. This article aims to review the available literature to present a concise updated concept on the regulation of male reproductive functions by the thyroid hormones, and the possible mechanism by which thyroid dysfunctions affects testicular functions.
Keywords: Thyroid hormone, Hypothyroidism, Hyperthyroidism, Steroidogenesis, Spermatogenesis, Semen quality, Infertility
How to cite this article:
Alahmar A, Dutta S, Sengupta P. Thyroid hormones in male reproduction and infertility. Asian Pac J Reprod 2019;8:203-10 |
| 1. Introduction | |  |
Thyroid hormones may modulate male reproductive functions by various routes, which have been the research interests since the past several decades. However, the exact mechanism of how thyroid hormones associate with male infertility remains elusive[1]. A global declining trend in semen quality over the last decades presents an alarming revelation on male fecundity[2],[3],[4],[5],[6]. To unveil the underlying causatives for such declining pattern in male fertility parameters, the endocrine regulations of male reproduction have been set forth as one of the major research interests. Male subfertility or infertility involves multivariate causatives with innumerable environmental and lifestyle factors leading to endogenous modulations[7],[8],[9],[10],[11]. They may disrupt the physiological hormonal milieu, among which one of the most important is the thyroid hormone profile that carries out versatile functions[5],[12] and also essentially determines normal male reproductive functions. The altered levels in thyroid hormones have deleterious impacts upon semen quality and male fertility[13].
The overall idea of thyroid hormone functions in the regulation of male reproduction can be contemplated through several studies[14],[15]. However, the mechanisms of how altered thyroid profile affects male fertility parameters are the subjects that are less delved[16]. This article thereby aims to review and present a concise updated knowledge on the general functions of thyroid hormones in regulating male reproductive functions and the possible mechanism by which thyroid disorders lead to altered testicular functions and semen quality.
| 2. Genomic and non-genomic effects of thyroid hormones on male reproduction | | |
Mechanism of action of thyroid hormones is mainly fulfilled through transcriptional regulation. Thyroid hormone nuclear receptors were found to be expressed in fetal and adult Sertoli cells[17]. Binding of triiodothyronine (T3) to its receptors in testicular cells activates gene transcription and protein synthesis as well as Sertoli cells proliferation and differentiation[18],[19]. The non-genomic effects may comprise binding of thyroid hormones to their nonnuclear receptors or to affect cell’s structure, metabolic rate, and proliferation of cells. However, the differences between genomic and nongenomic actions of the hormone have not yet clearly understood[20]. It was demonstrated that binding to nonnuclear receptors enhances the synthesis of cyclic adenosine monophosphate, the releasing of calcium, and the improvement of sperm kinetics. It was reported that addition of thyroxine (T4) to semen samples significantly increased hypermotility within 20 minutes[21]. Also, other iodothyronines could have an unknown non-genomic effect on spermatozoa by binding to its cytoskeleton or mitochondria[20].
Furthermore, thyroid hormones were known to regulate redox status and involve antioxidant systems[22]. Increased oxidative stress, due to neonatal hypothyroidism, has impaired the testicular glucose homeostasis, which may affect germ cell survival and proliferation as well as expression of proliferating cell nuclear antigen[23]. In transient hypothyroidism, there is higher protein carbonylation with a reduction in levels of superoxide dismutase (SOD), catalase, glutathione reductase, and glutathione peroxidase. While in the persistent type, only SOD and catalase levels were increased[24].
| 3. Impact of hypothyroidism on semen parameters and sex hormones | | |
Hypothyroidism is a pathological state of reduced circulating levels of T4 and T3 and increased thyroid stimulating hormone. Such decreased thyroid hormones have been reported to positively correlate with reduced serum testosterone level[25],[26]. This condition is related to several male reproductive disorders, such as hypoactive sexual behavior, erectile dysfunctions, delayed ejaculation, and deteriorated semen quality[27]. Hypothyroidism and male infertility have been associated through different studies[26],[28],[29] but it is not yet clear how hypothyroidism may directly affect semen quality[30].
3.1. Human studies
Hypothyroidism in men is not as common as found in women[31],[32], and its occurrence in men can be due to chronic exposure to various endocrine disruptors[33],[34]. It has been reported that hypothyroidism may cause a slight reduction in the serum levels of sex hormone-binding globulin (SHBG) and free testosterone as compared to that in the euthyroid men[31],[32]. The responsiveness of the gonadotropic cells of the anterior pituitary to gonadotropin-releasing hormone (GnRH) for the secretion of luteinizing hormone (LH) may get altered in hypothyroidism which leads to the altered hormonal milieu of the hypothalamic-pituitary-testicular axis[31]. It has been shown that T4 therapy could potentially result in an elevation of plasma testosterone level to normal in hypothyroid men[27].
Subclinical hypothyroidism in men has been shown to have insignificant impacts on semen quality in terms of sperm count, morphology and motility[35]. However, short-term post-pubertal hypothyroidism has been suggested to reduce semen volume[26],[36], sperm motility and secretions by the accessory glands[31],[32]. De la Balze et al demonstrated testicular histological abnormalities in six hypothyroid men with prepubertal/pubertal hypothyroidism. Through these observations it had been suggested that severe and prolonged hypothyroidism since childhood or puberty may lead to inhibition upon pituitary gonadotropins secretion that in turn may affect testicular morphology and functions[37]. Wortsman et al have found reduced levels of serum testosterone and concentrations of SHBG in most of the male subjects with hypothyroidism[25]. Corrales et al had also demonstrated that short-term post-pubertal hypothyroidism in men could not alter the testicular functions to the extent to deteriorate semen quality[26]. Jaya Kumar et al studied the male reproductive and endocrine functions in eight primary hypothyroid men. Their investigation proceeded from the hypothyroid state to the euthyroid state with T4 therapy. The study claimed some improvements in semen quality as the subjects achieved euthyroid state[36]. In a prospective controlled study, Krassas et al had also put forth that hypothyroidism impairs spermatogenesis, with alterations in sperm morphology and sperm motility[38].
3.2. Animal studies
Studies in rats demonstrated that hindering thyroid hormone secretions by antithyroidal drugs leads to spermatogenic arrest, reduction in seminiferous tubular diameter, seminal volume, weight of testicles, epididymis and prostate gland[39],[40],[41],[42]. Hypothyroidism in rats has also been associated with impairment in progressive sperm motility, transit time of sperm through the epididymis and secretions of the accessory glands[43],[44]. This condition also seems to affect sperm acrosome and mitochondrial functions[43]. Moreover, a significant decline in the number of viable testicular germ cells has been evident in rats with both transient and persistent hypothyroidism[24], which may attribute to reduced antioxidant capacity and induction of testicular oxidative stress[24],[41]. As thyroid hormones are essential for regulation of Sertoli cells differentiation, reduced levels of thyroid hormones after birth in rodents with congenital hypothyroidism have been shown to result in unregulated Sertoli cells proliferation and delay in their differentiation. This resulted in an uncontrolled high testicular weight and unregulated sperm production[45],[46].
3.3. Mechanism of action
Hypothyroidism characterized by reduced circulating levels of T3 and T4 may decrease SHBG concentrations and serum testosterone level, thereby impairing spermatogenesis. Thyroid insufficiency for a long period in childhood or puberty may lead to inhibition in pituitary gonadotropin secretions impeding gonadal growth, functions, secretory activities of the accessory glands, and may also induce erectile dysfunction, delayed ejaculation, lower libido and deteriorate semen quality. It also results in decreased seminiferous tubular diameter and net organ weight of testicles, epididymis and prostate gland thereby leading to impaired sperm development, sperm motility, and their transport through the epididymis. Sperm vitality may also get affected in conditions of hypothyroidism owing to the induction of testicular oxidative stress[47].
| 4. Impact of hyperthyroidism on semen parameters and sex hormones | | |
4.1. Human studies
Hyperthyroidism, a state of elevated serum total T4 levels is related to enhanced circulation levels of SHBG and reduced metabolic clearance rate of serum testosterone[48],[49]. Hyperthyroid men mainly suffer from subnormal levels of bioavailable testosterone[50] and an increase in circulating estradiol levels. These alterations in sex hormones may lead to gynecomastia[50], reduced libido[51] and occurrence of erectile dysfunction[52]. It is also evident that the LH and follicle-stimulating hormone responses are exaggerated towards the exogenous administration of GnRH in hyperthyroid men[30],[53]. The changes in the reproductive hormones profile thereby affect testicular functions and alter semen quality.
There are very few clinical studies that have correlated hyperthyroidism with semen quality. Clyde et al had reported that out of three hyperthyroid male patients in a clinical study, two was detected with oligozoospermia with reduced sperm motility, while the third had reduced sperm count besides having decreased sperm motility[54]. Kidd et al had also shown decreased sperm counts (<40 ×106/mL) in hyperthyroid men[49]. The clinical study by Hudson and Edwards in 1992 with 16 hyperthyroid men reported similar observations[55]. The study by Abalovich et al on the effect of hyperthyroidism on spermatogenesis in 21 male subjects showed that nine had reduced sperm counts, 18 had impaired sperm motility and 13 had defects in progressive sperm motility[50]. Krassas et al in a prospective study with 23 men had investigated semen parameters comparing the data with 15 euthyroid men used as control. They treated the hyperthyroid men with methimazole alone or in combination with radioiodine to render them euthyroid, while they performed semen analysis both pre- and post-treatment phases. The results showed slight reductions in mean sperm density, alterations in sperm morphology and significant reductions in mean sperm motility, as compared to controls[56]. They have demonstrated an improvement in sperm count and sperm motility after the tenure of treatment[56].
In humans, thyrotoxicosis which leads to an uncontrolled rise in levels of circulating thyroid hormones has been reported to be closely associated with asthenozoospermia, oligozoospermia and teratozoospermia. The conditions of excessive thyroid hormones in circulations lead to diminished semen volume (hypoposia)[30],[50].
4.2. Animal studies
There is a deficit in animal research on the association of hyperthyroidism and semen quality. Based on the reports from few noteworthy studies, it may be suggested that hyperthyroidism in rats may be associated with delayed spermatogenesis[46], the reduced diameter of the seminiferous tubules[39], and impaired mitochondrial activity[57]. A study has demonstrated that hyperthyroidism in murine model upregulates catalase activities, and downregulates glutathione peroxidase activities[40].
4.3. Mechanism of action
Hyperthyroidism is characterized by increased circulating T4 levels, compromised responsiveness of LH and follicle-stimulating hormone, altered endocrine profile, all of which result in impaired testicular functions, morphology, reduced seminiferous tubule diameter, delayed spermatogenesis, stunted sperm development and reduced sperm motility[25]. These disruptions in male reproductive functions cause low sperm count and deteriorated semen quality in hyperthyroid men. Hyperthyroidism-induced changes in the redox status of the testis, in the Leydig cells, Sertoli cells and germ cells, as well as impaired sperm mitochondrial activities, severely affect sperm count, vitality, and motility, thereby deteriorating semen quality[47].
| 5. Thyroid disorders and male reproductive dysfunctions | | |
5.1. Serum SHBG and androgen binding protein (ABP) levels
Altered thyroid status affects the liver and Sertoli cells production of both SHBG and ABP levels that transport testosterone. In thyrotoxicosis, SHBG, as well as testosterone, is increased due to the reduction in its metabolism[52]. However, ABP production by Sertoli cells was decreased in the culture medium following exgenous T3 administration[52].
5.2. Sexual dysfunction: libido and erectile dysfunction
Thyroid hormones, along with several other metabolic hormones, regulate the ejaculatory process. Thus, hypothyroidism has been recorded to be associated with delayed ejaculation. In contrast, premature ejaculation is related to hyperthyroidism[58]. In a multicenter trial to assess the prevalence of sexual dysfunctions in patients with thyroid disorders, hypoactive sexual desire, erectile dysfunction, and delayed ejaculation were recorded to be higher in hypothyroid patients (64.3%). The prevalence of premature ejaculation was higher in hyperthyroid patients (50.0%) than the hypothyroid counterparts (7.1%). Subsequent normalization of the thyroid hormone levels in hyperthyroid patients, premature ejaculation was declined to 15%, while delayed ejaculation was improved in half of the treated hypothyroid male patients[59]. In another survey that examined the effects of thyroid dysfunctions on male sexual health by using the Sexual Health Inventory for Males (SHIM), a significant difference was reported between patients and controls; 78.9% of patients with thyroid dysfunctions scored 21 or less (normal SHIM: 22-25) versus 33.8% of controls. However, following treatment, a significant increase in SHIM scores was noted in both hyperthyroid and hypothyroid patients (P<0.000 1). Also, a high prevalence of erectile dysfunction was noted in patients with hyperthyroid and hyperthyroid patients, compared to controls[60].
5.3. Spermatogenesis and semen parameters
Thyroid hormone is a major metabolic regulator of testicular development and function that could influence spermatogenesis[61]. Evidence from clinical and experimental studies in male rats/ human revealed that thyroid disorders (either excess or deficient), as well as altered thyroid status, are associated with controversial effects on male reproductive physiology. For instance, transient hypothyroidism in neonatal rats was associated with enlargements in testicular size[62], hyperthyroid patients were noted to have lower sperm motility, asthenozoospermia, oligozoospermia and teratozoospermia, compared to the control groups with euthyroid state[40],[63]. In addition, a recent study revealed a positive association of free T3 with ejaculate volume and seminal fructose levels[64].
Hypothyroid state could affect the sperm morphology and motility, and hence increase the incidence of teratozoospermia index. In patients with hypothyroidism, a significant difference was detected in semen parameters: sperm count, sperm motility and morphology as well as seminal vesicles longitudinal diameters.
Rodent models with induced hypothyroidism presented decreased sperm production, viable spermatozoa in the epididymis, and testicular germ cell count[24],[43]. It also reduces gonadal androgen receptor expression[65],[66], sperm motility, fertilizing capacity, and epididymal secretory activity. Additionally, it may affect the mitochondria such as alteration of mitochondrial lipid peroxidation[24], apoptotic changes in epididymal mitochondria[67], reduction in acrosome integrity and mitochondrial activity[43]. Moreover, an increase in the expression of thyroid hormones receptors (Thra1) and a decrease in the expression of deiodinases (Dio3) were associated with hypothyroidism, suggesting a critical metabolic role of thyroid hormones in spermatogenesis[43].
Rat models with hyperthyroidism also reflected a delayed spermatogenesis, maturational arrest, Leydig cell proliferation, reduction in the diameters of the seminiferous tubule, alteration in mitochondrial activity and antioxidant status. In addition, it increases the expression of monocarboxylate transporter 8 and plasma membrane integrity, solute carrier family 16 member 2[40],[46],[60],[68],[69].
| 6. Thyroid disorders and testicular oxidative stress | | |
6.1. Hyperthyroidism and testicular oxidative stress
Hyperthyroidism seems to render the tissues more vulnerable to oxidative damages[70],[71]. As thyroid hormones commonly invigorate physiological functions, it is quite inevitable that hyperthyroidism would overstimulate metabolic state, and upregulate excess free radical generation, resulting in oxidative damage and lipid peroxidation in different tissues[70],[72]. Testis, having a substantial amount of unsaturated fatty acids, potent machineries to generate reactive oxygen species along with limited antioxidant capacity[73], possesses much higher susceptibility towards oxidative damage compared to other tissues[74].
Studies have reported that induction of hyperthyroidism using different thyroid hormone isomers could result in varying levels of oxidative stress. The testicular oxidative stress has been suggested to get highly elevated in hyperthyroidism as it is evident via increased malondialdehyde levels[75], increased thiobarbituric acid reactive substances, high levels of lipid hydroperoxide, protein carbonyl contents or hydrogen peroxide[70]. Alterations in antioxidant defense parameters such as increased testicular glutathione (GSH) contents had been observed in case of short-term L-thyroxine treatment to hypothyroid[75]. Treatment with T3 to hypothyroid rats for 3 days showed elevated oxidized glutathione disulfide, decreased in GSH contents, and thereby decreased ratio of reduced to oxidized glutathione in testis[76]. T3 treatment for 5 days showed an increase in testicular GSH contents in mitochondrial as well as post- mitochondrial fractions, along with an increase in testicular ascorbic acid content[70]. Both the mitochondrial and post-mitochondrial fractions exhibited higher ‘reduced to oxidized’ glutathione ratio in L-thyroxine or T3 induced hyperthyroidism[24],[70].
Acute hyperthyroidism has been reported to be associated with decreased testicular SOD, while increased testicular catalase (CAT), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase activities[24],[70]. It has been shown that in mitochondrial and post-mitochondrial fractions of testis, GPx is increased by many folds in response to L-thyroxine[77]. In case of
T3 treatment, seleno-independent GPx activity was demonstrated to be increase only in the testicular mitochondrial fraction[70]. These elevated levels of seleno-dependent and/or independent GPx as responses of hyperthyroidism induction by L-thyroxine[77] or T3[70], may be considered as an adaptive response for neutralizing the testicular toxic hydrogen peroxide effects. Such hyperthyroidism-induced alterations in the testicular antioxidant defense mechanisms and oxidative stress parameters affect male fertility in terms of decreased viable and total sperm counts[24],[70].
6.2. Hypothyroidism and testicular oxidative stress
Hypothyroidism is also responsible for alterations in testicular redox status, oxidant generation and testicular antioxidant capacity owing to a hypo-metabolic state. Both persistent and transient hypothyroidism have been associated with changes in testicular antioxidant defense mechanism during gonadal development and maturation[73]. Hypothyroidism have been shown to modulate testicular oxidative stress parameters such as reduction in malondialdehyde levels[75] with elevated hydrogen peroxide, protein carbonyl contents, mitochondrial lipid peroxidase[78]. Protein carbonylation in mitochondrial membrane have also been used as a marker for oxidative damage in hypothyroid rat testis[77],[79].
In hypothyroid rats, lower levels of testicular GSH have been documented[75]. Contrarily, in hypothyroidism, oxidized glutathione content was shown to be higher which results in decreased ‘reduced to oxidized’ glutathione ratio in testis[76]. It has been reported that persistent hypothyroidism disrupts the normal testicular redox status in immature rats[77]. Decreased SOD and CAT activities as well as increased GPx activity with reduced glutathione-S-transferase have been demonstrated in the testis of hypothyroid rats[40],[76]. However, persistent hypothyroidism has been shown to elevate testicular SOD and CAT activities and reduce GPx and glutathione reductase activities[24]. Chronic hypothyroidism has also been shown to reduce both testicular seleno-dependent and independent GPx[77], which suggests that SOD and CAT are the key enzymes regulating of hypothyroidism-induced oxidative stress, not the GPx[73]. However, the reduced GPx levels affect the testosterone production in hypothyroid rats since the testosterone metabolism needs protection against peroxidation. Reduced serum levels of testosterone in turn impairs normal spermatogenesis leads to increased germ cell apoptosis, and thereby decreases testicular germ cell count and affects the semen quality[70],[73],[77],[80]. Further effects of hypothyroidism in the testicular morphology essentially include the reduced diameter of seminiferous tubule[77]. Hypothyroidism-induced alterations in testicular physiology may be reflected in adulthood with reduced fertility as evidenced through deteriorated semen quality in terms of germ cell viability[70] and sperm counts[73].
| 7. Crosstalk of thyroid hormones with other hormones and growth factors in regulating male reproductive functions | | |
7.1. Prolactin
The direct effect of physiological doses of prolactin on Sertoli cells was demonstrated to increase the synthesis of ABP, which plays a significant role in Sertoli cell proliferation and metabolism[81]. A study by Koivisto et al on the male Beagles reported a significant increase in prolactin level with a single intravenous injection of thyroxin in metoclopramide-induced short-term hyperprolactinemia. Of note, there were no changes in semen quality, LH, and testosterone levels[82]. However, markedly higher prolactin levels were demonstrated in hypothyroid patients in comparison with controls (P<0.001)[83].
7.2. Growth hormone
Increased levels of growth hormone and acromegaly could be associated with thyroid dysfunction. The prevalence of erectile dysfunction among 57 acromegalic subjects was 42.1% especially in a long disease duration[84].
7.3. Insulin-like growth factor (IGF)-1
By increasing the bioactivity of IGF3 via blocking IGF-binding proteins, T3 and IGF-3 were found to enhance proliferation and predominant differentiation of type A undifferentiated spermatogonia[85].
7.4. Leptin
Hypothyroidism is associated with weight gain and obesity[86]. Leptin is produced by the adipocytes and reported to have a central and peripheral effects on reproductive tissues. The expression of leptin receptors was observed in Leydig cells, prostate, and seminal vesicles, which influences male reproductive functions[87],[88],[89]. Leptin was found to inhibit testosterone in the testis[90],[91]; however, it has an indirect effect that could regulate the GnRH function[92]. Hyperleptinemia induces cytokine signaling-3 expression, inhibits phosphorylated signal transducer, and activates the transcription-3 expression. This resulted in a decline in the weight and volume of the testicles as well as the diameter of the seminiferous tubules and the numbers of spermatocytes[93],[94]. Also, there is an interaction between thyroid hormones and leptin; a positive correlation was recorded between thyroid stimulating hormone and leptin and body mass index[95]. In hypothyroid patients, serum leptin levels could be increased to overcome the gain of body weight caused by hypothyroidism[96].
| 8. Conclusions | | |
This review article has critically and concisely presented an updated concept on general functions of thyroid hormones in the regulation of male reproductive functions. Based on available reports, it also has put forth probable mechanism by which thyroid disorders may affect testicular physiology, resulting in altered semen quality. In doing so, the regulations of the testicular redox status via thyroid hormones have also been elucidated. However, the review finds that there are several gaps in concept in the proper molecular events that associate thyroid hormonal milieu with altered semen quality, which seeks further research interventions.
Conflict of interest statement
The authors declare that there is no conflict of interest.
| References | | |
| 1. | Krajewska-Kulak E, Sengupta P. Thyroid function in male infertility. Front Endocrinol (Lausanne ) 2013; 4: 174.  |
| 2. | Sengupta P. Reviewing reports of semen volume and male aging of last 33 years: From 1980 through 2013. Asian Pac J Reprod 2015; 4(3): 242-246. |
| 3. | Sengupta P, Borges EJr, Dutta S, Krajewska-Kulak E. Decline in sperm count in European men during the past 50 years. Hum Exp Toxicol 2018; 37(3): 247-255. |
| 4. | Sengupta P, Dutta S, Krajewska-Kulak E. The disappearing sperms: Analysis of reports published between 1980 and 2015. Am J Mens Health 2017; 11(4): 1279-1304. |
| 5. | Sengupta P, Dutta S, Tusimin MB, Irez T, Krajewska-Kulak E. Sperm counts in Asian men: Reviewing the trend of past 50 years. Asian Pac J Reprod 2018; 7(2): 87-92. |
| 6. | Sengupta P, Nwagha U, Dutta S, Krajewska-Kulak E, Izuka E. Evidence for decreasing sperm count in African population from 1965 to 2015. Afr Health Sci 2017; 17(2): 418-427. |
| 7. | Chandra A.K., Sengupta P, Goswami H, Sarkar M. Excessive dietary calcium in the disruption of structural and functional status of adult male reproductive system in rat with possible mechanism. Mol Cell Biochem 2012; 364(1-2): 181-191. |
| 8. | Sengupta P. Environmental and occupational exposure of metals and their role in male reproductive functions. Drug Chem Toxicol 2013; 36(3): 353368. |
| 9. | Sengupta P. Current trends of male reproductive health disorders and the changing semen quality. Int J Prev Med 2014; 5(1): 1-5. |
| 10. | Sengupta P. Recent trends in male reproductive health problems. Asian J Pharm Clin Res 2014; 7(2): 1-5. |
| 11. | Sengupta P, Banerjee R. Environmental toxins: Alarming impacts of pesticides on male fertility. Hum Exp Toxicol 2014; 33(10): 1017-1039. |
| 12. | Sengupta P, Dutta S. Metals. In: Skinner MK. (ed.) Reference module in biomedical sciences: Encyclopedia of reproduction. Cambridge: Academic Press; 2018, p. 579-587. |
| 13. | Rajender S, Monica MG, Walter L, Agarwal A. Thyroid, spermatogenesis, and male infertility. Front Biosci (Elite Ed) 2011; 3: 843-855. |
| 14. | Wajner SM, Wagner MS, Maia AL. Clinical implications of altered thyroid status in male testicular function. Arq Bras Endocrinol Metab 2010; 53(8): 976-982. |
| 15. | Kumar A, Shekhar S, Dhole B. Thyroid and male reproduction. Indian J Endocrinol Metab 2014; 18(1): 23-31. |
| 16. | Sharma MK, Parchwani D, Maheria P, Upadhyah A. Relationship between thyroid profile and semen quality. Nat J Comm Med 2012; 3(1): 20- 24. |
| 17. | Jannini EA, Crescenzi A, Rucci N, Screponi E, Carosa E, De Matteis A, et al. Ontogenetic pattern of thyroid hormone receptor expression in the human testis. J Clin Endocrinol Metab 2000; 85(9): 3453-3457. |
| 18. | Holsberger DR, Cooke PS. Understanding the role of thyroid hormone in Sertoli cell development: A mechanistic hypothesis. Cell Tissue Res 2005; 322(1): 133-140. |
| 19. | Jannini EA, Ulisse S, D’Armiento M. Thyroid hormone and male gonadal function. Endocr Rev 1995; 16(4): 443-459. |
| 20. | Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol 2016; 12(2): 111-121. |
| 21. | Mendeluk GR, Rosales M. Thyroxin is useful to improve sperm motility. Int J Fertil Steril 2016; 10(2): 208-214. |
| 22. | La Vignera S, Vita R, Condorelli RA, Mongioì LM, Presti S, Benvenga S, et al. Impact of thyroid disease on testicular function. Endocrine 2017; 58(3): 397-407. |
| 23. | Sarkar D, Singh SK. Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: Effects on GLUT3, GLUT8 and Cx43. Andrology 2017; 5(4): 749-762. |
| 24. | Sahoo DK, Roy A, Bhanja S, Chainy GB. Hypothyroidism impairs antioxidant defence system and testicular physiology during development and maturation. Gen Comp Endocrinol 2008; 156(1): 63-70. |
| 25. | Wortsman J, Rosner W, Dufau ML. Abnormal testicular function in men with primary hypothyroidism. Am J Med 1987; 82(2): 207-212. |
| 26. | Corrales Hernandez JJ, Miralles Garcia JM, Garcia Diez LC. Primary hypothyroidism and human spermatogenesis. Arch Androl 1990; 25(1): 21- 27. |
| 27. | Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab 2005; 90(12): 64726479. |
| 28. | Meikle AW. The interrelationships between thyroid dysfunction and hypogonadism in men and boys. Thyroid 2004 ;14(Suppl 1): S17-25. |
| 29. | Patel N, Kashanian JA. (eds). Thyroid dysfunction and male reproductive physiology. Seminars in reproductive medicine. New York: Thieme Medical Publishers; 2016. |
| 30. | Krassas GE, Pontikides N. Male reproductive function in relation with thyroid alterations. Best Pract Res Clin Endocrinol Metab 2004; 18(2): 183-195. |
| 31. | Bjoro T, Holmen J, Kruger O, Midthjell K, Hunstad K, Schreiner T, et al. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord- Trondelag (HUNT). Eur J Endocrinol 2000; 143(5): 639-647. |
| 32. | Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160(4): 526-534. |
| 33. | Chandra AK, Goswami H, Sengupta P. Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats. Indian J Exp Biol 2014; 52(8): 787-792. |
| 34. | Chandra AK, Goswami H, Sengupta P. Dietary calcium induced cytological and biochemical changes in thyroid. Environ Toxicol Pharmacol 2012; 34(2): 454-465. |
| 35. | Trummer H, Ramschak-Schwarzer S, Haas J, Habermann H, Pummer K, Leb G. Thyroid hormones and thyroid antibodies in infertile males. Fertil Steril 2001; 76(2): 254-257. |
| 36. | Jaya Kumar B, Khurana ML, Ammini AC, Karmarkar MG, Ahuja MM. Reproductive endocrine functions in men with primary hypothyroidism: Effect of thyroxine replacement. Horm Res 1990; 34(5-6): 215-218. |
| 37. | De La Balze FA, Arrillaga F, Mancini RE, Janches M, Davidson OW, Gurtman AI. Male hypogonadism in hypothyroidism: A study of six cases. J Clin Endocrinol Metab 1962; 22: 212-222. |
| 38. | Krassas GE, Papadopoulou F, Tziomalos K, Zeginiadou T, Pontikides N. Hypothyroidism has an adverse effect on human spermatogenesis: A prospective, controlled study. Thyroid 2008; 18(12): 1255-1259. |
| 39. | Fadlalla MB, Wei Q, Fedail JS, Mehfooz A, Mao D, Shi F. Effects of hyper- and hypothyroidism on the development and proliferation of testicular cells in prepubertal rats. Anim Sci J 2017; 88(12): 1943-1954. |
| 40. | Choudhury S, Chainy GB, Mishro MM. Experimentally induced hypo- and hyper-thyroidism influence on the antioxidant defence system in adult rat testis. Andrologia 2003; 35(3): 131-140. |
| 41. | Sarkar D, Singh SK. Effect of neonatal hypothyroidism on prepubertal mouse testis in relation to thyroid hormone receptor alpha 1 (THRalpha1). Gen Comp Endocrinol 2017; 251: 109-120. |
| 42. | Maran RR, Arunakaran J, Aruldhas MM. T3 directly stimulates basal and modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro. Endocr J 2000; 47(4): 417-428. |
| 43. | Romano RM, Gomes SN, Cardoso NC, Schiessl L, Romano MA, Oliveira CA. New insights for male infertility revealed by alterations in spermatic function and differential testicular expression of thyroid-related genes. Endocrine 2017; 55(2): 607-617. |
| 44. | Anbalagan J, Sashi AM, Vengatesh G, Stanley JA, Neelamohan R, Aruldhas MM. Mechanism underlying transient gestational-onset hypothyroidism-induced impairment of posttesticular sperm maturation in adult rats. Fertil Steril 2010; 93(8): 2491-2497. |
| 45. | Lara NLM, Franca LR. Neonatal hypothyroidism does not increase Sertoli cell proliferation in iNOS(-/-) mice. Reproduction 2017; 154(1): 13-22. |
| 46. | Rijntjes E, Wientjes AT, Swarts HJ, de Rooij DG, Teerds KJ. Dietary- induced hyperthyroidism marginally affects neonatal testicular development. JAndrol 2008; 29(6): 643-653. |
| 47. | Sengupta P, Dutta S. Thyroid Disorders and Semen Quality. Biomed Pharm J 2018; 11(1): 1-10. |
| 48. | Vermeulen A, Verdonck L, Van Der Straeten M, Orie N. Capacity of the testosterone-binding globulin in human plasma and influence of specific binding to testosterone on its metabolic clearance rate. J Clin Endocrinol Metab 1969; 29: 1470-1480. |
| 49. | Kidd GS, Glass AR, Vigersky RA. The hypothalamic-pituitary-testicular axis in thyrotoxicosis. J Clin Endocrinol Metab 1979; 48(5): 798-802. |
| 50. | Abalovich M, Levalle O, Hermes R, Scaglia H, Aranda C, Zylbersztein C, et al. Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males. Thyroid 1999; 9(9): 857-863. |
| 51. | Velazquez EM, Bellabarba Arata G. Effects of thyroid status on pituitary gonadotropin and testicular reserve in men. Arch Androl 1997; 38(1): 8592. |
| 52. | Singh R, Hamada AJ, Agarwal A. Thyroid hormones in male reproduction and fertility. Open Reprod Sci J 2011; 3: 98-104. |
| 53. | Zahringer S, Tomova A, von Werder K, Brabant G, Kumanov P, Schopohl J. The influence of hyperthyroidism on the hypothalamic-pituitary- gonadal axis. Exp Clin Endocrinol Diabetes 2000; 108(4): 282-289. |
| 54. | Clyde HR, Walsh PC, English RW. Elevated plasma testosterone and gonadotropin levels in infertile males with hyperthyroidism. Fertil Steril 1976; 27(6): 662-666. |
| 55. | Hudson RW, Edwards AL. Testicular function in hyperthyroidism. J Androl 1992; 13(2): 117-124. |
| 56. | Krassas GE, Pontikides N, Deligianni V, Miras K. A prospective controlled study of the impact of hyperthyroidism on reproductive function in males. J Clin Endocrinol Metab 2002; 87(8): 3667-3671. |
| 57. | Giarenis I, Mastoroudes H, Cardozo L, Robinson D. What do we do when a midurethral tape fails? Rediscovery of open colposuspension as a salvage continence operation. Int Urogynecol J 2012; 23(8): 1117-1122. |
| 58. | Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol 2012; 9(9): 508-519. |
| 59. | Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab 2005; 90(12): 64726479. |
| 60. | Krassas GE, Papadopoulou F, Tziomalos K, Zeginiadou T, Pontikides N. Hypothyroidism has an adverse effect on human spermatogenesis: A prospective, controlled study. Thyroid 2008; 18(12): 1255-1259. |
| 61. | Wagner MS, Wajner SM, Maia AL. The role of thyroid hormone in testicular development and function. J Endocrinol 2008; 199(3): 351-365. |
| 62. | Cooke PS, Meisami E. Early hypothyroidism in rats causes increased adult testis and reproductive organ size but does not change testosterone levels. Endocrinology 1991; 129(1): 237-243. |
| 63. | Krassas GE, Pontikides N, Deligianni V, Miras K. A prospective controlled study of the impact of hyperthyroidism on reproductive function in males. J Clin Endocrinol Metab 2002; 87(8): 3667-3671. |
| 64. | Lotti F, Maseroli E, Fralassi N, Degl’Innocenti S, Boni L, Baldi E, et al. Is thyroid hormones evaluation of clinical value in the work-up of males of infertile couples? Hum Reprod 2016; 31(3): 518-529. |
| 65. | Anbalagan J, Sashi AM, Vengatesh G, Stanley JA, Neelamohan R, Aruldhas MM. Mechanism underlying transient gestational-onset hypothyroidism-induced impairment of posttesticular sperm maturation in adult rats. Fertil Steril 2010; 93(8): 2491-2497. |
| 66. | Aruldhas MM, Ramalingam N, Jaganathan A, Sashi AMJ, Stanley JA, Nagappan AS, et al. Gestational and neonatal-onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood. Prostate 2010; 70(7): 689-700. |
| 67. | Palaoro LA, Rocher AE, Canessa OE, Peressini S, Rosales M, Del Río AG, et al. Epididymal mitochondrial status of hypothyroid rats examined by transmission electron microscopy. Biotech Histochem 2013; 88(3-4): 138-144. |
| 68. | Hassan MH, Ibrahim HM, El-Taieb MA. 25-Hydroxy cholecalciferol, anti-Müllerian hormone, and thyroid profiles among infertile men. Aging Male 2018; 22: 1-7. |
| 69. | Abalovich M, Levalle O, Hermes R, Scaglia H, Aranda C, Zylbersztein C, et al. Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males. Thyroid 2009; 9(9): 857-863. |
| 70. | Sahoo DK, Chainy G. Tissue specific response of antioxidant defence systems of rat to experimentally-induced hyperthyroidism. Nat Acad Sci Lett 2007; 30(7-8): 247-250. |
| 71. | Sahoo DK, Roy A, Chainy GB. Protective effects of vitamin E and curcumin on L-thyroxine-induced rat testicular oxidative stress. Chem Biol Interact 2008; 176(2-3): 121-128. |
| 72. | Das K, Chainy G. Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone. Biochim Biophys Acta 2001; 1537(1): 1-13. |
| 73. | Sahoo D, Roy A, Chainy G. Rat testicular mitochondrial antioxidant defence system and its modulation by aging. Acta Biol Hungarica 2008; 59(4): 413-424. |
| 74. | Darbandi M, Darbandi S, Agarwal A, Sengupta P, Durairajanayagam D, Henkel R, et al. Reactive oxygen species and male reproductive hormones. Reprod Biol Endocrinol 2018; 16(1): 87. |
| 75. | Mogulkoc R, Baltaci AK, Oztekin E, Aydin L, Tuncer I. Hyperthyroidism causes lipid peroxidation in kidney and testis tissues of rats: Protective role of melatonin. Neuroendocrinol Lett 2005; 26(6): 806-810. |
| 76. | Choudhury S, Chainy G, Mishro M. Experimentally induced hypo-and hyper-thyroidism influence on the antioxidant defence system in adult rat testis. Andrologia 2003; 35(3): 131-140. |
| 77. | Sahoo D. Alterations of testicular selenium-dependent and independent glutathione peroxidase activities during experimentally L-thyroxine induced hyperthyroidism and n-propyl thiouracil induced hypothyroidism in adult rats. Res Rev Biosci 2012; 6(3): 85-91. |
| 78. | Choudhury S, Chainy GBN, Mishro MM. Experimentally induced hypo-and hyper-thyroidism influence on the antioxidant defence system in adult rat testis. Andrologia 2003; 35(3): 131-140. |
| 79. | Chattopadhyay S, Sahoo DK, Roy A, Samanta L, Chainy GB. Thiol redox status critically influences mitochondrial response to thyroid hormone-induced hepatic oxidative injury: A temporal analysis. Cell Biochem Func 2010; 28(2): 126-134. |
| 80. | Chandra R, Aneja R, Rewal C, Konduri R, Dass SK, Agarwal S. An opium alkaloid-Papaverine ameliorates ethanol-induced hepatotoxicity: Diminution of oxidative stress. Indian J Clin Biochem 2000; 15(2): 155-160. |
| 81. | Scarabelli L, Caviglia D, Bottazzi C, Palmero S. Prolactin effect on pre- pubertal Sertoli cell proliferation and metabolism. J Endocrinol Investig 2003; 26(8): 718-722. |
| 82. | Koivisto MB, Eschricht F, Urhausen C, Hoppen HO, Beyerbach M, Oei CHY, et al. Effects of short-term hyper- and hypoprolactinaemia on hormones of the pituitary, gonad and -thyroid axis and on semen quality in male beagles. Reprod Domest Anim 2009; 44(Suppl 2): 320-325. |
| 83. | Nikoobakht MR, Aloosh M, Nikoobakht N, Mehrsay A, Biniaz F, Karjalian MA. The role of hypothyroidism in male infertility and erectile dysfunction. Urol J 2012; 9(1): 405-409. |
| 84. | Lotti F, Rochira V, Pivonello R, Santi D, Galdiero M, Maseroli E, et al. Erectile dysfunction is common among men with acromegaly and is associated with morbidities related to the disease. J Sex Med 2015; 12(5): 1184-1193. |
| 85. | Safian D, Morais RDVS, Bogerd J, Schulz RW. Igf binding proteins protect undifferentiated spermatogonia in the zebrafish testis against excessive differentiation. Endocrinology 2016; 157(11): 4423-4433. |
| 86. | Dutta S, Biswas A, Sengupta P. Obesity, endocrine disruption and male infertility. Asian Pac J Reprod 2019; 8(5): 195-202. |
| 87. | Malendowicz W, Rucinski M, Macchi C, Spinazzi R, Ziolkowska A, Nussdorfer GG, et al. Leptin and leptin receptors in the prostate and seminal vesicles of the adult rat. Int J Mol Med 2006; 18(4): 615-618. |
| 88. | Caprio M, Isidori AM, Carta AR, Moretti C, Dufau ML, Fabbri A. Expression of functional leptin receptors in rodent Leydig cells. Endocrinology 1999; 140(11): 4939-4947. |
| 89. | Sengupta P, Bhattacharya K, Dutta S. Leptin and male reproduction. Asian Pac J Reprod 2019; 8(5): 220-226. |
| 90. | Tena-Sempere M, Pinilla L, González LC, Diéguez C, Casanueva FF, Aguilar E, (eds.). Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol 1999; 161(2): 221-218.. |
| 91. | Dutta S, Sengupta P, Biswas A. Adiponectin in male reproduction and infertility. Asian Pac J Reprod 2019; 8(5): 244-250. |
| 92. | Quennell JH, Mulligan AC, Tups A, Liu X, Phipps SJ, Kemp CJ, et al. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology 2009; 150(6): 2805-2812. |
| 93. | Yuan M, Huang G, Li J, Zhang J, Li F, Li K, et al. Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process. Reprod Biol Endocrinol 2014; 12(1): 15. |
| 94. | Sengupta P, Arafa M. Hormonal Regulation of Spermatogenesis. In: Singh R. (ed.) Molecular signaling in spermatogenesis and male infertility. New Delhi: Elsevier; 2019. |
| 95. | Menendez C, Baldelli R, Camiña JP, Escudero B, Peino R, Dieguez C, et al. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol 2003; 176(1): 7-12. |
| 96. | Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol 1998; 157(1): 75-79. |
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