The simultaneous administration of microplastics and cadmium alters rat testicular activity and changes the expression of PTMA, DAAM1 and PREP

Abstract

This paper confirms the damaging effects produced by MP and Cd on testicular activity in the rat. Oral treatment with both chemicals resulted in testicular damage, documented by biomolecular and histological alterations, particularly by impaired morphometric parameters, increased apoptosis, reduced testosterone synthesis, and downregulation of the steroidogenic enzyme 3β-HSD. We also demonstrated, for the first time, that both MP and Cd can affect the protein level of PTMA, a small peptide that regulates germ cell proliferation and differentiation. Interestingly, the cytoarchitecture of testicular cells was also altered by the treatments, as evidenced by the impaired expression and localization of DAAM1 and PREP, two proteins involved in actin- and microtubule-associated processes, respectively, during germ cells differentiation into spermatozoa, impairing normal spermatogenesis. Finally, we showed that the effect of simultaneous treatment with MP and Cd were more severe than those produced by MP alone and less harmful than those of Cd alone. This could be due to the different ways of exposure of the two substances to rats (in drinking water for Cd and in oral gavage for MP), since being the first contact in the animals’ gastrointestinal tract, MP can adsorb Cd, reducing its bioavailability through the Trojan-horse effect.

Expression of RSPH6A in the first wave of rat spermatogenesis and oxidative stress conditions: Attenuation by melatonin

“…As expected, results showed that 40 days of Cd treatment provoked a significant reduction in RSPH6A level in both the testis and SPZ. This data further confirms the detrimental action of Cd, which alters testicular activity at various levels, including steroidogenesis, 27,43 blood-testis barrier integrity, 19,21 cytoarchitecture of the cells composing the seminiferous epithelium, 18,25,26 and sperm parameters, especially motility. 8,21 Interestingly, the antioxidant ability of Mlt to counteract the Cd-induced effect was evidenced again, as only a slight decrease in RSPH6A expression was observed in the group treated simultaneously with Mlt and Cd.…”

“… 15 Among the environmental substances directly involved in growing infertility, Cd is a heavy metal with a very long half‐life 16 that acts as an endocrine disruptor 17 , 18 and induces oxidative stress. 19 , 20 , 21 , 22 Cd deleterious effects on health and on the fertility rate are widely studied, 23 since Cd impairs spermatogenesis, 18 , 21 , 24 , 25 , 26 , 27 finally leading to a reduction in sperm quantity and quality, specifically by reducing SPZ motility. 28 , 29 …”

“…15 Among the environmental substances directly involved in growing infertility, Cd is a heavy metal with a very long half-life 16 that acts as an endocrine disruptor 17,18 and induces oxidative stress. [19][20][21][22] Cd deleterious effects on health and on the fertility rate are widely studied, 23 since Cd impairs spermatogenesis, 18,21,[24][25][26][27] finally leading to a reduction in sperm quantity and quality, specifically by reducing SPZ motility. 28,29 Because Cd exposure is an inevitable phenomenon, numerous studies have concentrated on research to identify the precise molecular targets of Cd effects and, therefore, find potential ameliorative or suppressive molecules that could be utilized in new therapeutic advances.…”

Melatonin counteracts cadmium‐induced rat testicular toxicity via the mechanistic target rapamycin (mTOR) pathway

“…It should be noted that the whole spermatogenic process, including the events that occur in the dynamics of BTB and GC transit through the lumen, is regulated by T (Venditti, Romano, et al, 2021). T biosynthesis is catalyzed by specific sets of steroid enzymes, such as StAR and 3β‐HSD, which are sensitive to external environmental pollutants (Venditti et al, 2021a; Venditti, Romano, et al, 2021; Venditti et al, 2023). Rapa has been shown to increase T levels that are reduced by silencing the zinc transporter family 4 ( ZnT4 ) gene through the phosphatidylinositol 3‐kinase/Akt/mTOR autophagy pathway in TM3 mouse Leydig cells (Li et al, 2023).…”

D-Aspartate Depletion Perturbs Steroidogenesis and Spermatogenesis in Mice

“…Cell differentiation during spermatogenesis requires a proper cytoskeleton dynamic, regulated by several proteins [ 24 ], such as prolyl endopeptidase (PREP) and disheveled-associated activator of morphogenesis 1 (DAAM1), which play key roles in the postnatal development of the rat testis [ 25 , 26 ] and, as for PREP, in sperm motility [ 27 , 28 ]. Moreover, as we have found their altered expression and localization in pathological and/or altered spermatogenesis [ 29 , 30 , 31 , 32 ], we raised the possibility of their use as potential new markers of proper fertility. Specifically, PREP is a binding partner of tubulin [ 25 ]; it also directly limits GnRH stimulation of the pituitary gonadotropes by cleaving its C-terminal glycinamide residue, as demonstrated in rat and ovine hypothalamic extracts [ 33 , 34 ].…”