Histopathological effects of long-term exposure to realistic concentrations of cadmium in the hepatopancreas of Sparus aurata juveniles.

In recent decades, cadmium has emerged as an environmental stressor in aquatic ecosystems due to its persistence and toxicity. It can enter water bodies from various natural and anthropogenic sources and, once introduced into aquatic systems, can accumulate in sediments and biota, leading to bioaccumulation and biomagnification in the food chain. For this reason, the effects of cadmium on aquatic life remain an area of ongoing research and concern. In this paper, a multidisciplinary approach was used to assess the effects of long-term exposure to an environmental concentration on the hepatopancreas of farmed juveniles of sea bream, Sparus aurata. After determining metal uptake, metallothionein production was assessed to gain insight into the organism's defence response. The effects were also assessed by histological and ultrastructural analyses. The results indicate that cadmium accumulates in the hepatopancreas at significant concentrations, inducing structural and functional damage. Despite the parallel increase in metallothioneins, fibrosis, alterations in carbohydrate distribution and endocrine disruption were also observed. These effects would decrease animal fitness although it did not translate into high mortality or reduced growth. This could depend on the fact that the animals were farmed, protected from the pressure deriving from having to search for food or escape from predators. Not to be underestimated is the return to humans, as this species is edible. Understanding the behaviour of cadmium in aquatic systems, its effects at different trophic levels and the potential risks to human health from the consumption of contaminated seafood would therefore be essential for informed environmental management and policy decisions.

Could Exposure to Glyphosate Pose a Risk to the Survival of Wild Animals? A Case Study on the Field Lizard Podarcis siculus.

Soil contaminants (herbicides, pesticides, and heavy metals) are among the main causes of change in terrestrial ecosystems. These substances lead to a general loss of biodiversity, both of flora and fauna and being able to biomagnify and pass through the food chain, they can endanger the survival of terrestrial vertebrates at the top of this chain. This review analyzes the risks associated with exposure to glyphosate, the active principle of many herbicide products, for the reproductive health of the field lizard (Podarcis siculus) potentially exposed to the substance in its natural habitat; therefore, introducing it as a possible model organism. Data demonstrate that glyphosate is toxic for this animal, affecting the health of the reproductive organs, both in males and females, and of the liver, the main detoxifying organ and closely involved in the female reproductive process. Sharing structural and functional characteristics of these organs with many other vertebrates, the information obtained with this reptile represents a wake-up call to consider when analyzing the cost/benefit ratio of glyphosate-based substances. The data clearly demonstrate that the P. siculus lizard can be considered a good target organism to study the reproductive risk assessment and hazards of exposure to soil contaminants on wild terrestrial vertebrates.

Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells.

Phthalates are a family of aromatic chemical compounds mainly used as plasticizers. Among phthalates, di-n-butyl phthalate (DBP) is a low-molecular-weight phthalate used as a component of many cosmetic products, such as nail polish, and other perfumed personal care products. DBP has toxic effects on reproductive health, inducing testicular damage and developmental malformations. Inside the male reproductive system, the prostate gland reacts to both male and female sex steroids. For this reason, it represents an important target of endocrine-disrupting chemicals (EDCs), compounds that are able to affect the estrogen and androgen signaling pathways, thus interfering with prostate homeostasis and inducing several prostate pathologies. The aim of this project was to investigate the effects of DBP, alone and in combination with testosterone (T), 17ß-estradiol (E2), and both, on the normal PNT1A human prostate cell-derived cell line, to mimic environmental contamination. We showed that DBP and all of the tested mixtures increase cell viability through activation of both estrogen receptor α (ERα) and androgen receptor (AR). DBP modulated steroid receptor levels in a nonmonotonic way, and differently to endogenous hormones. In addition, DBP translocated ERα to the nucleus over different durations and for a more prolonged time than E2, altering the normal responsiveness of prostate cells. However, DBP alone seemed not to influence AR localization, but AR was continuously and persistently activated when DBP was used in combination. Our results show that DBP alone, and in mixture, alters redox homeostasis in prostate cells, leading to a greater increase in cell oxidative susceptibility. In addition, we also demonstrate that DBP increases the migratory potential of PNT1A cells. In conclusion, our findings demonstrate that DBP, alone and in mixtures with endogenous steroid hormones, acts as an EDC, resulting in an altered prostate cell physiology and making these cells more prone to cancer transformation.

Cocaine Effects on Reproductive Behavior and Fertility: An Overview.

Cocaine is one of the most widely used drugs that, due to its molecular properties, causes various behavioral alterations, including sexual behavior. In vivo and in vitro studies conducted mainly in mammals have shown various disorders of sexual activity and morpho-functional dysfunctions of the gonads in both sexes. Although the modalities are still unclear, cocaine has been shown to alter the cell cycle, induce apoptosis, and alter sperm motility. In females, this drug alters the formation of the meiotic spindle as well as may obstruct the ovulation mechanism of mature oocytes. The data provided in this review, in addition to reviewing the current literature on the main effects of cocaine on spermatogenesis and oogenesis mainly in mammals, will hopefully provide a basic overview that may help and support further future studies on the molecular interaction of cocaine and its metabolites with germ cells.

Glyphosate Interference in Follicular Organization in the Wall Lizard Podarcis siculus.

Glyphosate (Gly) is a broad-spectrum herbicide widely used thanks to its high efficiency and low toxicity. However, evidence exists of its toxic effects on non-target organisms. Among these, the animals inhabiting agricultural fields are particularly threatened. Recent studies demonstrated that exposure to Gly markedly affected the morphophysiology of the liver and testis of the Italian field lizard Podarcis siculus. The present study aimed to investigate the effects of the herbicide on the female reproductive system of this lizard in order to have a full picture of Gly-induced reproductive impairment. The animals were exposed to 0.05 and 0.5 µg/kg of pure Gly by gavage for 3 weeks. The results demonstrated that Gly, at both doses tested, profoundly interfered with ovarian function. It induced germ cells' recruitment and altered follicular anatomy by anticipating apoptotic regression of the pyriform cells. It also induced thecal fibrosis and affected oocyte cytoplasm and zona pellucida organizations. At the functional levels, Gly stimulated the synthesis of estrogen receptors, suggesting a serious endocrine-disrupting effect. Overall, the follicular alterations, combined with those found at the level of the seminiferous tubules in males, suggest serious damage to the reproductive fitness of these non-target organisms, which over time could lead to a decline in survival.

Biological and metabolic effects of the association between the microalga Galdieria sulphuraria and the fungus Penicillium citrinum.

Contamination of microalgae cultures can reduce their productivity and affect the quality of biomass and valuable bioproducts. In this article, after having isolated and identified for the first time the filamentous fungus Penicillium citrinum from heterotrophic cultures of the red polyextremophilic microalga Galdieria sulphuraria, we investigated the biological and metabolic significance of this alga-fungus association. In the same medium, both organisms grow better in each other's presence than separately. Both cell density and cell size of G. sulphuraria increase in co-cultures compared to pure alga cultures. In co-cultures, despite very severe growth conditions, the load of P. citrinum increases compared to pure fungus cultures. Optical microscope images have shown physical contact between cells of P. citrinum hyphae and G. sulphuraria which, however, retain their morphology and cell wall intact. GC-MS-based metabolomics analysis of metabolites excreted in the culture medium shows that pure cultures of the fungus and alga and co-cultures of alga plus fungus can be easily differentiated based on their metabolic products. Indeed, a richer assortment of extracellular metabolites (comprising both products of primary and secondary metabolism) is a distinct feature of co-cultures compared to both pure alga and pure fungus cultures.

Transmission Electron Microscopy: A Method for Studying the Adrenal Chromaffin Cells.

Transmission electron microscopy and the use of glutaraldehyde-osmium fixation allow to distinguish norepinephrine from epinephrine granules in the adrenochromaffin cells, a difficult distinction with histochemical methods if both types of granules are present in the same cell. Here we describe all the steps necessary to process the adrenochromaffin tissue for the transmission electron microscopy; this protocol is suitable for any kind of adrenal tissue, and personally we used it in mammals, reptiles, and amphibians.

Juniperus oxycedrus L. ssp. Essential Oil Microneedles: A Promising Antimicrobial and Wound Healing Activity.

The use of essential oil (EO) in treating infected wounds is still challenging. A lot of effort has been made to make such an application more convenient. Recently, microneedles (MNDs) have been considered as a smart dermal delivery system to overcome the poor absorption and distribution, low bioavailability, and skin penetration of some drugs. The aim of our study is to evaluate the wound healing activity of juniper-EO-loaded MNDs (EO MNDs) against wounds with bacterial and fungal infection. The Polyvinylpyrrolidone (PVP) MNDs were prepared using the gel-filled mold technique and loaded with juniper EO. In vivo models were created and wounds on rats were infected with two clinically isolated bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, Candida albicans was used to mimic fungal infection and juniper EO MNDs were tested. The obtained results showed an improvement in wound healing which started from the third day after application of the juniper EO MNDs, and at the sixth day post-infection, the treated wounds were significantly smaller than untreated wounds. A complete healing was shown by the 12th day after infection. Furthermore, our cytotoxicity results showed a cytotoxic effect of juniper EO MNDs on epithelial cells, which explained the faster wound healing in rats. Our study showed that juniper EO MNDs represent a novel strategy in EO delivery with minimal invasion. Juniper EO MNDs demonstrated significant antimicrobial activity against both the bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus and against one fungal strain, Candida albicans. Finally, application of juniper EO MNDs exerted promising activity in the treatment and healing of wound infection.

The Italian Wall Lizard Podarcis siculus as a Biological Model for Research in Male Reproductive Toxicology.

Spermatogenesis is a genetically driven differentiation process that occurs in the testis and leads to the formation of spermatozoa. This process is extensively studied in several experimental models, particularly in vertebrates that share the morphological structure and functionality of the mammalian testis. Although reptiles are not generally considered biological models, the lizard Podarcis siculus has represented a suitable organism for the study of spermatogenesis over the years. In this lizard, the process of spermatogenesis is regulated by the interaction between systemic factors such as gonadotropins and local factors, i.e., molecules produced by the somatic and germinal cells of the testis. Many exogenous substances are able to alter the production of these regulative factors, thus altering the course of spermatogenesis, and P. siculus has proven to be an excellent model for studying the effects of various endogenous or exogenous substances on mechanisms underlying spermatogenesis. This review summarizes the available data on the effects of different substances on the control of spermatogenesis, highlighting the induced morphological and molecular alterations. Overall, the data show that sex hormone levels as well as the final stages of spermatogenesis are most affected by an imbalance of endogenous compounds or contamination by environmental pollutants. This is helpful for the male individual, since the damage, not affecting the spermatogonial stem cells, can be considered transient and not irreversible.

Aquatic Pollution and Risks to Biodiversity: The Example of Cocaine Effects on the Ovaries of Anguilla anguilla.

Pollution is one of the main causes of the loss of biodiversity, currently one of the most important environmental problems. Important sources of aquatic pollution are illicit drugs, whose presence in waters is closely related to human consumption; their psychoactive properties and biological activity suggest potential adverse effects on non-target organisms, such as aquatic biota. In this study, we evaluated the effect of an environmentally relevant concentration of cocaine (20 ng L−1), an illicit drug widely found in surface waters, on the ovaries of Anguilla anguilla, a species critically endangered and able to accumulate cocaine in its tissues following chronic exposure. The following parameters were evaluated: (1) the morphology of the ovaries; (2) the presence and distribution of enzymes involved in oogenesis; (3) serum cortisol, FSH, and LH levels. The eels exposed to cocaine showed a smaller follicular area and a higher percentage of connective tissue than controls (p < 0.05), as well as many previtellogenic oocytes compared with controls having numerous fully vitellogenic and early vitellogenic oocytes. In addition, the presence and location of 3ß-hydroxysteroid dehydrogenase, 17ß-hydroxysteroid dehydrogenase, and P450 aromatase differed in the two groups. Finally, cocaine exposure decreased FSH and LH levels, while it increased cortisol levels. These findings show that even a low environmental concentration of cocaine affects the ovarian morphology and activity of A. anguilla, suggesting a potential impact on reproduction in this species.

Molecular and Histological Effects of Glyphosate on Testicular Tissue of the Lizard Podarcis siculus.

The expansion of agriculture produces a steady increase in habitat fragmentation and degradation due to the increased use of pesticides and herbicides. Habitat loss and alteration associated with crop production play an important role in reptile decline, among which lizards are particularly endangered. In this study, we evaluated testicular structure, steroidogenesis, and estrogen receptor expression/localization after three weeks of oral exposure to glyphosate at 0.05 and 0.5 µg/kg body weight every other day in the field lizard Podarcis siculus. Our results show that glyphosate affected testicular morphology, reduced spermatogenesis, altered gap junctions and changed the localization of estrogen receptors in germ cells, increasing their expression; the effects were mostly dose-dependent. The result also demonstrates that glyphosate, at least at these concentrations, did not influence steroidogenesis. Overall, the data indicate that this herbicide can disturb the morphophysiology of the male lizard's reproductive system, with obviously detrimental effects on their reproductive fitness. The effects of glyphosate must be considered biologically relevant and could endanger the reproductive capacity not only of lizards but also of other vertebrates, including humans; a more controlled and less intensive use of glyphosate in areas devoted to crop production would therefore be advisable.

Sulfur Starvation in Extremophilic Microalga Galdieria sulphuraria: Can Glutathione Contribute to Stress Tolerance?

This study reports the effects of sulfur (S) deprivation in cultures of Galdieria sulphuraria (Cyanidiophyceae). Galdieria is a unicellular red alga that usually grows, forming biomats on rocks, in S-rich environments. These are volcanic areas, where S is widespread since H2S is the prevalent form of gas. The glutathione content in Galdieria sulphuraria is much higher than that found in the green algae and even under conditions of S deprivation for 7 days, it remains high. On the other hand, the S deprivation causes a decrease in the total protein content and a significant increase in soluble protein fraction. This suggests that in the conditions of S starvation, the synthesis of enzymatic proteins, that metabolically support the cell in the condition of nutritional stress, could be up regulated. Among these enzymatic proteins, those involved in cell detoxification, due to the accumulation of ROS species, have been counted.

Heart Mitochondrial Metabolic Flexibility and Redox Status Are Improved by Donkey and Human Milk Intake.

The biological mechanisms linking nutrition and antioxidants content of the diet with cardiovascular protection are subject of intense investigation. It has been demonstrated that dietary supplementation with cow, donkey or human milk, characterized by distinct nutritional properties, triggers significant differences in the metabolic and inflammatory status through the modulation of hepatic and skeletal muscle mitochondrial functions. Cardiac mitochondria play a key role for energy-demanding heart functions, and their disfunctions is leading to pathologies. Indeed, an altered heart mitochondrial function and the consequent increased reactive oxygen species (ROS) production and inflammatory state, is linked to several cardiac diseases such as hypertension and heart failure. In this work it was investigated the impact of the milk consumption on heart mitochondrial functions, inflammation and oxidative stress. In addition, it was underlined the crosstalk between mitochondrial metabolic flexibility, lipid storage and redox status as control mechanisms for the maintenance of cardiovascular health.

The Aromatase-Estrogen System in the Testes of Non-Mammalian Vertebrates.

Estrogens are important physiological regulators of testicular activity in vertebrates. Estrogen levels depend on the activity of P450 aromatase, the enzyme responsible for the irreversible conversion of testosterone into 17ß-estradiol. Therefore, P450 aromatase is the key player in the aromatase-estrogen system. The present review offers a comparative overview of P450 aromatase activity in male gonads of amphibians, reptiles, and birds, with a particular emphasis on the functions of the aromatase-estrogen system in these organisms during their developmental and adult stages. The aromatase-estrogen system appears to be crucial for the sex differentiation of gonads in vertebrates. Administration of aromatase inhibitors prior to sexual differentiation of gonads results in the development of males rather than females. In adults, both aromatase and estrogen receptors are expressed in somatic cells, Leydig and Sertoli cells, as well as germ cells, with certain differences among different species. In seasonal breeding species, the aromatase-estrogen system serves as an "on/off" switch for spermatogenesis. In some amphibian and reptilian species, increased estrogen levels in post-reproductive testes are responsible for blocking spermatogenesis, whereas, in some species of birds, estrogens function synergistically with testosterone to promote spermatogenesis. Recent evidence indicates that the production of the aromatase enzyme in excessive amounts reduces the reproductive performance in avian species of commercial interest. The use of aromatase inhibitors to improve fertility has yielded suitable positive results. Therefore, it appears that the role of the aromatase-estrogen system in regulating the testicular activity differs not only among the different classes of vertebrates but also among different species within the same class.

Proliferative and Apoptotic Pathways in the Testis of Quail Coturnix coturnix during the Seasonal Reproductive Cycle.

The quail Coturnix coturnix is a seasonal breeding species, with the annual reproductive cycle of its testes comprising an activation phase and a regression phase. Our previous results have proven that the testicular levels of both 17ß-estradiol (E2) and androgens are higher during the reproductive period compared to the non-reproductive period, which led us to hypothesize that estrogens and androgens may act synergistically to initiate spermatogenesis. The present study was, therefore, aimed to investigate the estrogen responsive system in quail testis in relation to the reproduction seasonality, with a focus on the molecular pathways elicited in both active and regressive quail testes. Western blotting and immunohistochemistry analysis revealed that the expression of ERα, which is the predominant form of estrogen receptors in quail testis, was correlated with E2 concentration, suggesting that increased levels of E2-induced ERα could play a key role in the resumption of spermatogenesis during the reproductive period, when both PCNA and SYCP3, the mitotic and meiotic markers, respectively, were also increased. In the reproductive period we also found the activation of the ERK1/2 and Akt-1 kinase pathways and an increase in second messengers cAMP and cGMP levels. In the non-reproductive phase, when the E2/ERα levels were low, the inactivation of ERK1/2 and Akt-1 pathways favored apoptotic events due to an increase in the levels of Bax and cytochrome C, with a consequent regression of the gonad.

JNK/Elk1 signaling and PCNA protein expression in the brain of hibernating frog Pelophylax esculentus.

Mitogen activated protein kinase (MAPK) activation and neurogenesis are known to play a role in neuronal survival during hibernation. Herein, we investigate the activity of c-Jun N-terminal kinases (JNK) and Ets like-1 protein (Elk1) kinase involved in cell survival, as well as the expression of proliferating cell nuclear antigen (PCNA), a cell proliferation marker, in the brain of the frog Pelophylax esculentus. The study was conducted on female and male frogs collected during the annual cycle. Our results demonstrated that JNK activity increased during the hibernating phase in relation to the active phase. Interestingly, P-Elk1 levels were positively correlated with P-JNK levels, suggesting that the JNK/Elk1 pathway is pivotal in mediating neuroprotective adaptations that are essential to successful hibernation. On the contrary, we detected higher PCNA expression levels during the active period compared with the hibernating period. A sex dimorphism was observed in the expression levels of P-JNK/P-Elk1 that were specifically higher in males, and in the expression of PCNA reporting higher levels in female brains. Much remains to be learned regarding the regulation of hibernation, however, our findings provide new insights into the role of MAPK and proliferative pathways in hibernation, adding new knowledge concerning the mechanisms activated in the brain of ectothermic species to counteract the damage resulting from extreme temperatures.

Alkyphenol Exposure Alters Steroidogenesis in Male Lizard Podarcis siculus.

BACKGROUND: Nonylphenol (NP) and Octylphenol (OP) are persistent and non-biodegradable environmental contaminants classified as endocrine disruptor chemicals (EDCs). These compounds are widely used in several industrial applications and present estrogen-like properties, which have extensively been studied in aquatic organisms. The present study aimed to verify the interference of these compounds alone, and in mixture, on the reproductive cycle of the male terrestrial vertebrate Podarcis siculus, focusing mainly on the steroidogenesis process. METHODS: Male lizards have been treated with different injections of both NP and OP alone and in mixture, and evaluation has been carried out using a histological approach. RESULTS: Results obtained showed that both substances are able to alter both testis histology and localization of key steroidogenic enzymes, such as 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß- hydroxysteroid dehydrogenase (17ß-HSD) and P450 aromatase. Moreover, OP exerts a preponderant effect, and the P450 aromatase represents the major target of both chemicals. CONCLUSIONS: In conclusion, NP and OP inhibit steroidogenesis, which in turn may reduce the reproductive capacity of the specimens.

OctylPhenol (OP) Alone and in Combination with NonylPhenol (NP) Alters the Structure and the Function of Thyroid Gland of the Lizard Podarcis siculus.

Different environmental contaminants disturb the thyroid system at many levels. AlkylPhenols (APs), by-products of microbial degradation of AlkylPhenol Polyethoxylates (APEOs), constitute an important class of Endocrine Disrupting Chemicals (EDCs), the two most often used environmental APs being 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP). The purpose of the present study was to investigate the effects on the thyroid gland of the bioindicator Podarcis siculus of OP alone and in combination with NP. We used radioimmunoassay to determine their effects on plasma 3,3',5-triiodo-L-thyronine (T3), 3,3',5,5'-L-thyroxine (T4), thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) levels in adult male lizards. We also investigated the impacts of AP treatments on hepatic 5'ORD (type II) deiodinase and hepatic content of T3 and T4. After OP and OP + NP administration, TRH levels increased, whereas TSH, T3, and T4 levels decreased. Lizards treated with OP and OP + NP had a higher concentration of T3 in the liver and 5'ORD (type II) activity, whereas T4 concentrations were lower than that observed in the control group. Moreover, histological examination showed that the volume of the thyroid follicles became smaller in treated lizards suggesting that that thyroid follicular epithelial cells were not functionally active following treatment. This data collectively suggest a severe interference with hypothalamus-pituitary-thyroid axis and a systemic imbalance of thyroid hormones.

Effects of environmental cocaine concentrations on COX and caspase-3 activity, GRP-78, ALT, CRP and blood glucose levels in the liver and kidney of the European eel (Anguilla anguilla).

Cocaine is one of the most widely used illicit drugs in the world, and as a result of incomplete removal by sewage treatment plants it is found in surface waters, where it represents a new potential risk for aquatic organisms. In this study we evaluated the influence of environmental concentrations of cocaine on the liver and the kidney of the European eel (Anguilla anguilla). The eels were exposed to 20 ng L-1 of cocaine for fifty days, after which, three and ten days after the interruption of cocaine exposure their livers and kidneys were compared to controls. The general morphology of the two organs was evaluated, as well as the following parameters: cytochrome oxidase (COX) and caspase-3 activities, as markers of oxidative metabolism and apoptosis activation, respectively; glucose-regulated protein (GRP)78 levels, as a marker of endoplasmic reticulum (ER)-stress; blood glucose level, as stress marker; serum levels of alanine aminotransferase (ALT), as a marker of liver injury and serum levels of C-reactive protein (CRP), as a marker of the inflammatory process. The liver showed morphologic alterations such as necrotic areas, karyolysis and pyknotic nuclei, while the kidneys had dilated glomeruli and the renal tubules showed pyknotic nuclei and karyolysis. In the kidney, the alterations persisted after the interruption of cocaine exposure. In the liver, COX and caspase-3 activities increased (COX: P = 0.01; caspase-3: P = 0.032); ten days after the interruption of cocaine exposure, COX activity returned to control levels (P = 0.06) whereas caspase-3 activity decreased further (P = 0.012); GRP78 expression increased only in post-exposure recovery specimens (three days: P = 0.007 and ten days: P = 0.008 after the interruption of cocaine exposure, respectively). In the kidney, COX and caspase-3 activities increased (COX: P = 0.02; caspase-3: P = 0.019); after the interruption of cocaine exposure, COX activity remained high (three days: P = 0.02 and ten days: P = 0.029 after the interruption of cocaine exposure, respectively) whereas caspase-3 activity returned to control values (three days: P = 0.69 and ten days: P = 0.67 after the interruption of cocaine exposure, respectively). Blood glucose and serum ALT and CRP levels increased (blood glucose: P = 0.01; ALT: P = 0.001; CRP: 0.015) and remained high also ten days after the interruption of cocaine exposure (blood glucose: P = 0.009; ALT: P = 0.0031; CRP: 0.036). These results suggest that environmental cocaine concentrations adversely affected liver and kidney of this species.

Spermatogenesis and regulatory factors in the wall lizard Podarcis sicula.

Spermatogenesis is an extraordinarily complex process, regulated by several factors, which leads to the differentiation of spermatogonia into spermatozoa. Among vertebrates, several reports have been focused on the lizard Podarcis sicula, a seasonal breeder and a good model for the study of reproductive processes. The goal of this review is to resume all the available data about systemic and above all local control factors involved in the control of P. sicula testicular activity. During the seasonal reproductive cycle, the variation of the expression levels of these factors determines significant variations that induce the activation or blocking of spermatogenesis. The data supplied in this review, in addition to analyze the current literature regarding the main actors of Podarcis sicula spermatogenesis, will hopefully provide a basic model that can be used for further studies on the intratesticular interaction between molecular factors that control spermatogenesis.