Research Projects

Thyroid dysfunction is one of the most prevalent endocrine disorder affecting an estimated 200 million people globally (1). Its impact on male fertility has long been overlooked, largely due to the believe that estes are unresponsive to thyroid hormones (2). Later, the correlation between thyroid hormones and the testes was established (3). The hypothalamic-pituitary-gonadal (HPG) axis orchestrates the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which regulates the secretion of sex hormones vital for sexual maturation, testicular activity, and overall reproductive health (4). Kisspeptin acts as a crucial regulator of GnRH release, which stimulates the HPG axis and testosterone production (5). Disruptions in the HPG axis leads to reproductive health issues like hypogonadism, impaired spermatogenesis and infertility (6). Testis is a target organ for thyroid hormones, as thyroid hormone receptors are abundantly present in testicular cell types (7). The impact of T3 in regulating Sertoli cell proliferation and functional maturation is well established, along with its participation in postnatal differentiation and steroidogenesis of Leydig cells (8). So, thyroid hormones are regarded as essential integrators of male reproductive functions and play vital roles in male gonadal development. Thyroid disorders affect testicular function and influence reproduction by altering the interaction between the hypothalamic-pituitary-thyroid (HPT) and HPG axes (9). Various bioactive peptides are known to treat the thyroid dysfunction like P19 (cyclic peptide), exenatide, A-type natriuretic peptide (ANP), B-type natriuretic peptide (BNP) (10-12). Adropin, a 43 amino acid hepatic peptide, was discovered by Kumar et al, which is encoded by energy homeostasis associated gene. Adropin elicits its biological actions via GPR19 (13). Adropin plays crucial role in maintaining gluco-lipid homeostasis (14). Besides its metabolic roles, adropin plays vital role in regulating various important processes such as inflammation, antioxidant defence, and endothelial cell functions (15). Adropin's function in male reproductive system is poorly understood. We recently reported that adropin is localized in Leydig cells only, while GPR19 is found in advanced spermatocytes and Leydig cells (16). Also, adropin enhances testicular functions and redox potential in adult mice testes (17). Moreover, altered thyroid status has been shown to be detrimental to testicular functions and circulating adropin level decreases in both hyper and hypothyroidic rat (18). However, role of adropin in altered thyroid status associated testicular dysfunction is not yet demonstrated. So, we hypothesize that adropin may modulate GnRH and gonadotropin secretion, thereby influencing testicular functions under altered thyroid conditions. Therefore, this project aims to investigate the role of adropin in regulation of testicular functions during thyroid dysfunction using mice model.