Research Projects

Chemerin, also known as retinoic acid receptor responder 2 (RARRES2), is a recently identified adipokine expressed in various tissues (Estienne et al., 2019). It plays a role in several physiological processes, particularly under pathological conditions, and is linked to glucose homeostasis, insulin sensitivity, and glucose uptake. Chemerin is also expressed in the ovaries and testes, indicating its involvement in reproductive regulation (Dupont et al., 2015). Notably, it can influence reproductive hormone dynamics by modulating gonadotropin levels (Bobjer et al., 2017). Diabetes mellitus is a multifaceted endocrine disorder frequently associated with insulin resistance, obesity, and impaired spermatogenesis, all of which contribute to male infertility and reproductive dysfunction (La Vignera et al., 2012; Shaikh et al., 2016). The testis, being metabolically active organ, is particularly vulnerable to oxidative stress, hormonal imbalances, and cellular degeneration under diabetic conditions (Asadi et al., 2017). As a result, both testicular architecture and function are markedly disrupted, largely due to oxidative stress, depletion of antioxidant defences, reduced cellular proliferation, and enhanced apoptosis (Biasi et al., 2025). Diabetes has been widely reported to cause impaired gonadotropins signaling (LH and FSH), leading to impaired Leydig cell function and reduced testosterone production (Ballester et al., 2004). In streptozotocin (STZ)-induced diabetic mice, this hormonal imbalance is well-documented and contributes to testicular dysfunction and reduced steroidogenesis (Abd El-Hakim et al., 2020). Moreover, elevated circulating chemerin levels have been observed in STZ-diabetic mice, with growing evidence supporting its role in reproductive impairment (Wang et al., 2017; Lin et al., 2019) α-NETA (2-(α-Naphthoyl)ethyltrimethylammonium iodide), a selective antagonist of the chemerin receptor CMKLR1, has demonstrated biological efficacy in modulating inflammatory and metabolic pathways (Peng et al., 2023). However, its role in reproductive regulation, specifically in relation to testicular activity, spermatogenesis, and endocrine function during diabetes condition remains largely unexplored. Despite emerging evidence linking chemerin dysregulation to reproductive impairments, there exists a significant gap in understanding the therapeutic potential of α-NETA in mitigating testicular dysfunction under diabetic conditions, particularly through modulation of the Hypothalamic-Pituitary-Gonadal (HPG) axis. Addressing this knowledge gap may provide valuable insights into novel strategies for managing diabetes-associated male reproductive dysfunction. Accordingly, the present study aims to investigate the effects of chemerin inhibition using α-NETA on testicular function in streptozotocin-induced diabetic mice, with a specific focus on the modulation of the hypothalamic-pituitary-gonadal (HPG) axis.