The use of bisphenols has become extremely common in our daily lives. Due to the extensive toxic effects of Bisphenol A (BPA), the industry has replaced this endocrine-disrupting chemical (EDC) with its analogues, which have been proven to decrease testosterone levels via several mechanisms, including targeting the steroidogenic acute regulatory (StAR) protein. However, when exposed to BPA and its analogues, the specific mechanism that emerges to target StAR protein regulations remains uncertain. Hence, this review discusses the effects of BPA and its analogues in StAR protein regulation by targeting cAMP-PKA, PLC-PKC, EGFR-MAPK/ERK and Ca2+-Nur77. BPA and its analogues mainly lead to decreased LH in blood and increased ERK expression and Ca2+ influx, with no relationship with the StAR protein regulation in testicular steroidogenesis. Furthermore, the involvement of the cAMP-PKA, PLC-PKC, and Nur77 molecules in StAR regulation in Leydig cells exposed to BPA and its analogues remains questionable. In conclusion, although BPA and its analogues have been found to disrupt the StAR protein, the evidence in connecting the signaling pathways with the StAR regulations in testicular steroidogenesis is still lacking, and more research is needed to draw a solid conclusion.

The cryopreservation of spermatogonia stem cells (SSCs) has been widely used as an alternative treatment for infertility. However, cryopreservation itself induces cryoinjury due to oxidative and osmotic stress, leading to reduction in the survival rate and functionality of SSCs. Glial-derived neurotrophic factor family receptor alpha 1 (GFRα1) and promyelocytic leukemia zinc finger (PLZF) are expressed during the self-renewal and differentiation of SSCs, making them key tools for identifying the functionality of SSCs. To the best of our knowledge, the involvement of GFRα1 and PLZF in determining the functionality of SSCs after cryopreservation with therapeutic intervention is limited. Therefore, the purpose of this review is to determine the role of GFRα1 and PLZF as biomarkers for evaluating the functionality of SSCs in cryopreservation with therapeutic intervention. Therapeutic intervention, such as the use of antioxidants, and enhancement in cryopreservation protocols, such as cell encapsulation, cryoprotectant agents (CPA), and equilibrium of time and temperature increase the expression of GFRα1 and PLZF, resulting in maintaining the functionality of SSCs. In conclusion, GFRα1 and PLZF have the potential as biomarkers in cryopreservation with therapeutic intervention of SSCs to ensure the functionality of the stem cells.

Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERβ functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERβ in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERβ in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.