In both animals and human beings, numerous studies have highlighted a rising trend in male infertility, largely driven by a progressive decline in semen quality and motility. However, the underlying causes of this decline remain poorly understood. Hence, the identification of putative diagnostic biomarkers is essential for elucidating the underlying mechanisms responsible for impaired sperm motility and for improving our understanding of the importance of sperm motility-associated molecules in diagnosing male infertility. The primary emphasis of this review article is to consolidate studies on sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) and highlight its significance as a promising biomarker of sperm motility. Although oxidative phosphorylation was considered as a major source of energy production in spermatozoa, numerous investigations have substantiated glycolysis as the primary metabolic pathway facilitating sperm motility and hyperactivation. GAPDHS is specially compartmentalized in the principal piece of mammalian spermatozoa to support sperm motility through the continued production of ATP. Knockout models revealed its pivotal role in male fertility. A growing body of research reported that deficits in GAPDHS expression and enzyme activity lead to poor sperm motility and male infertility. Therefore, GAPDHS emerges as a promising biomarker for sperm motility with potential relevance to male infertility diagnosis. Nevertheless, the available evidence is currently insufficient to establish GAPDHS as a clinically validated diagnostic biomarker, and further studies specifically addressing its diagnostic accuracy, sensitivity, specificity, and clinical utility are warranted. GAPDHS may also have broader biological roles beyond spermatozoa, although these aspects are only briefly considered in this review.
The development of trophoblast organoids (TOs) has revolutionized placental research by providing proliferative, three-dimensional systems recapitulating the key aspects of placental architecture and function. These models have become invaluable tools for studying trophoblast differentiation and early placental development. Importantly, TOs also offer new opportunities for investigating mechanisms underlying pregnancy-related disorders such as preeclampsia or fetal growth restriction, and host-pathogen interactions, advancing our understanding of how infections impact early pregnancy. However, the relevance and translatability of experimental outcomes strongly depend on aligning the research question with the most appropriate model system. Despite their potential, current models still lack critical physiological components, including vascular and immune elements. This review discusses TOs application in translational science and highlights future directions toward integrating these systems into more complex microphysiological platforms to better model human placental function and disease. These advances not only deepen our understanding of placental biology but also pave the way for clinically relevant applications, notably to guide therapeutic interventions in pregnancy-related disorders.
Asthenozoospermia, a common cause of male infertility characterized by reduced sperm motility, has been linked to oxidative stress and ferroptosis. Long non-coding RNAs (lncRNAs) are emerging regulators of redox balance and cell death. This study aimed to investigate the expression profile of the lncRNA taurine upregulated gene 1 (TUG1) and its relationship with ferroptosis-related dysfunction in spermatozoa from men with asthenozoospermia. Semen samples were collected from Iranian men with asthenozoospermia and normozoospermic controls. A bioinformatic screen of ferroptosis-associated lncRNAs identified TUG1 as a candidate biomarker, with several isoforms predicted to be dysregulated in asthenozoospermic sperm. Quantitative real-time PCR was used to assess the expression of TUG1, the ferroptosis-suppressing antioxidant enzyme gene glutathione peroxidase 4 (GPX4), and the somatic-cell markers CD5 and CD34. Lipid peroxidation was quantified by measuring malondialdehyde (MDA) levels. Associations among gene expression, oxidative stress markers, body mass index (BMI), and semen parameters were analyzed. Asthenozoospermic men exhibited significant upregulation of TUG1 and downregulation of GPX4 compared with normozoospermic controls. Elevated MDA levels positively correlated with TUG1 expression and inversely with GPX4 mRNA level, suggesting increased oxidative stress and possible ferroptosis-related involvement. Reduced expression of CD5 and CD34 confirmed efficient removal of somatic-cell contamination. Higher BMI was negatively correlated with sperm motility indices. Altered expression of TUG1 and GPX4 in asthenozoospermic sperm is consistent with involvement of ferroptosis-related pathways in impaired motility. These findings provide mechanistic insight into oxidative-stress-mediated sperm dysfunction and may inform future diagnostic and therapeutic strategies for male infertility.
