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

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.

[1]  Hengyi Xu,et al.  Male reproductive toxicity of polystyrene microplastics: Study on the endoplasmic reticulum stress signaling pathway. , 2022, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[2]  J. Mendiola,et al.  Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries. , 2022, Human reproduction update.

[3]  Zongping Liu,et al.  Mechanisms of Cadmium-Induced Testicular Injury: A Risk to Male Fertility , 2022, Cells.

[4]  M. Venditti,et al.  First Evidence of the Expression and Localization of Prothymosin α in Human Testis and Its Involvement in Testicular Cancers , 2022, Biomolecules.

[5]  Shuping Zhang,et al.  Distinct adverse outcomes and lipid profiles of erythrocytes upon single and combined exposure to cadmium and microplastics. , 2022, Chemosphere.

[6]  Linchuan Fang,et al.  Microplastics addition reduced the toxicity and uptake of cadmium to Brassica chinensis L. , 2022, The Science of the total environment.

[7]  Hui Yang,et al.  Comparison of the combined toxicity of polystyrene microplastics and different concentrations of cadmium in zebrafish. , 2022, Aquatic toxicology.

[8]  Beibei Liu,et al.  Antagonistic effect of polystyrene nanoplastics on cadmium toxicity to maize (Zea mays L.). , 2022, Chemosphere.

[9]  Yu Yan,et al.  Bioaccessibility of microplastic-associated heavy metals using an in vitro digestion model and its implications for human health risk assessment , 2022, Environmental Science and Pollution Research.

[10]  B. E. Ehigiator,et al.  Chronic toxic effects of polystyrene microplastics on reproductive parameters of male rats , 2022, Environmental analysis, health and toxicology.

[11]  M. Venditti,et al.  New Insight on the In Vitro Effects of Melatonin in Preserving Human Sperm Quality , 2022, International journal of molecular sciences.

[12]  M. J. Bragado,et al.  Sperm Phosphoproteome: Unraveling Male Infertility , 2022, Biology.

[13]  M. Itoh,et al.  Microenvironment for spermatogenesis and sperm maturation , 2022, Histochemistry and Cell Biology.

[14]  Minghao Yan,et al.  Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway , 2022, Particle and Fibre Toxicology.

[15]  Minghao Yan,et al.  Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway , 2022, Particle and Fibre Toxicology.

[16]  M. Venditti,et al.  Potential protective effect of lactic acid bacteria against zearalenone causing reprotoxicity in male mice. , 2022, Toxicon : official journal of the International Society on Toxinology.

[17]  C. Cheng,et al.  Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models , 2022, Cells.

[18]  M. Banni,et al.  Exposure to microplastics leads to a defective ovarian function and change in cytoskeleton protein expression in rat , 2022, Environmental Science and Pollution Research.

[19]  M. Venditti,et al.  Differential Expression and Localization of EHBP1L1 during the First Wave of Rat Spermatogenesis Suggest Its Involvement in Acrosome Biogenesis , 2022, Biomedicines.

[20]  Yunyi Wang,et al.  Comparing the effects of polystyrene microplastics exposure on reproduction and fertility in male and female mice. , 2021, Toxicology.

[21]  B. Silvestrini,et al.  Signaling Proteins That Regulate Spermatogenesis Are the Emerging Target of Toxicant-Induced Male Reproductive Dysfunction , 2021, Frontiers in Endocrinology.

[22]  D. Pröfrock,et al.  Microplastics as a Trojan horse for trace metals , 2021 .

[23]  R. Reiter,et al.  Evidence of melatonin ameliorative effects on the blood-testis barrier and sperm quality alterations induced by cadmium in the rat testis. , 2021, Ecotoxicology and environmental safety.

[24]  Chaonan Zhang,et al.  Single and Combined Effects of Microplastics and Cadmium on the Cadmium Accumulation and Biochemical and Immunity of Channa argus , 2021, Biological Trace Element Research.

[25]  Lianju Shen,et al.  Polystyrene microplastics disrupt the blood-testis barrier integrity through ROS-Mediated imbalance of mTORC1 and mTORC2. , 2021, Environmental pollution.

[26]  M. Venditti,et al.  Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins, DAAM1 and PREP, in Human Testicular Disorders , 2021, International journal of molecular sciences.

[27]  R. Reiter,et al.  Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis , 2021, Genes.

[28]  A. Fucic,et al.  Environmental and Occupational Exposures Associated with Male Infertility , 2021, Arhiv za higijenu rada i toksikologiju.

[29]  N. Xu,et al.  Polystyrene microplastics induce blood–testis barrier disruption regulated by the MAPK-Nrf2 signaling pathway in rats , 2021, Environmental Science and Pollution Research.

[30]  F. Aniello,et al.  Preliminary Investigation on the Ameliorative Role Exerted by D-Aspartic Acid in Counteracting Ethane Dimethane Sulfonate (EDS) Toxicity in the Rat Testis † , 2021, Animals : an open access journal from MDPI.

[31]  Xianhai Yang,et al.  Enhanced toxicity of triphenyl phosphate to zebrafish in the presence of micro- and nano-plastics. , 2020, The Science of the total environment.

[32]  R. Reiter,et al.  First evidence of the protective role of melatonin in counteracting cadmium toxicity in the rat ovary via the mTOR pathway. , 2020, Environmental pollution.

[33]  Fangyi Wang,et al.  Reproductive toxicity of polystyrene microplastics: In vivo experimental study on testicular toxicity in mice. , 2020, Journal of hazardous materials.

[34]  Weitao Liu,et al.  Do polystyrene nanoplastics affect the toxicity of cadmium to wheat (Triticum aestivum L.)? , 2020, Environmental pollution.

[35]  Aldo Donizetti,et al.  EH domain binding protein 1-like 1 (EHBP1L1), a protein with calponin homology domain, is expressed in the rat testis , 2020, Zygote.

[36]  Ming Yan,et al.  Microtubule cytoskeleton and spermatogenesis - Lesson from studies of toxicant models. , 2020, Toxicological sciences : an official journal of the Society of Toxicology.

[37]  Yabing Chen,et al.  Polystyrene microplastics induced male reproductive toxicity in mice. , 2020, Journal of hazardous materials.

[38]  Ming Yan,et al.  Actin binding proteins, actin cytoskeleton and spermatogenesis - Lesson from toxicant models. , 2020, Reproductive toxicology.

[39]  Qiqi Zhu,et al.  Toxicological Effects of Cadmium on Mammalian Testis , 2020, Frontiers in Genetics.

[40]  A. Agarwal,et al.  Environmental contaminants and male infertility: Effects and mechanisms , 2020, Andrologia.

[41]  M. Venditti,et al.  D-Aspartate Upregulates DAAM1 Protein Levels in the Rat Testis and Induces Its Localization in Spermatogonia Nucleus , 2020, Biomolecules.

[42]  M. Venditti,et al.  Cadmium‐induced toxicity increases prolyl endopeptidase (PREP) expression in the rat testis , 2020, Molecular reproduction and development.

[43]  A. Sinisi,et al.  DAAM1 and PREP are involved in human spermatogenesis. , 2020, Reproduction, fertility, and development.

[44]  L. Politano,et al.  Study of expression of genes potentially responsible for reduced fitness in patients with myotonic dystrophy type 1 and identification of new biomarkers of testicular function , 2019, Molecular reproduction and development.

[45]  L. Rosati,et al.  D-Asp Upregulates PREP and GluA2/3 Expressions and Induces p-ERK1/2 and p-Akt in Rat Testis. , 2019, Reproduction.

[46]  F. Aniello,et al.  Study on PREP localization in mouse seminal vesicles and its possible involvement during regulated exocytosis , 2019, Zygote.

[47]  C. Weder,et al.  Emergence of Nanoplastic in the Environment and Possible Impact on Human Health. , 2019, Environmental science & technology.

[48]  M. Venditti,et al.  Subcellular Localization of Prolyl Endopeptidase During the First Wave of Rat Spermatogenesis and in Rat and Human Sperm , 2018, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[49]  O. Tsitsilonis,et al.  In vitro immunodetection of prothymosin alpha in normal and pathological conditions. , 2019, Current medicinal chemistry.

[50]  M. O’Bryan,et al.  The Cytoskeleton in Spermatogenesis. , 2019, Reproduction.

[51]  C. Wyns,et al.  Fertility and infertility: Definition and epidemiology. , 2018, Clinical biochemistry.

[52]  I. Huhtaniemi MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms. , 2018, European journal of endocrinology.

[53]  F. Aniello,et al.  First evidence of DAAM1 localization in mouse seminal vesicles and its possible involvement during regulated exocytosis. , 2018, Comptes rendus biologies.

[54]  C. Picut,et al.  Comparative Aspects of Pre‐ and Postnatal Development of the Male Reproductive System , 2018, Birth defects research.

[55]  M. Venditti,et al.  Involvement of testicular DAAM1 expression in zinc protection against cadmium‐induced male rat reproductive toxicity , 2018, Journal of cellular physiology.

[56]  M. Venditti,et al.  Prothymosin alpha expression in the vertebrate testis: a comparative review , 2017, Zygote.

[57]  Niels Jørgensen,et al.  Temporal trends in sperm count: a systematic review and meta-regression analysis , 2017, Human reproduction update.

[58]  Q. Lian,et al.  Cell polarity, cell adhesion, and spermatogenesis: role of cytoskeletons , 2017, F1000Research.

[59]  B. Lemos,et al.  Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure , 2017, Scientific Reports.

[60]  C. Cheng,et al.  Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis? , 2016, Seminars in cell & developmental biology.

[61]  Aldo Donizetti,et al.  First Evidence of DAAM1 Localization During the Post‐Natal Development of Rat Testis and in Mammalian Sperm , 2016, Journal of cellular physiology.

[62]  Efsa Publication Statement on the presence of microplastics and nanoplastics in food, with particular focus on seafood , 2016 .

[63]  Aldo Donizetti,et al.  Prothymosin alpha expression and localization during the spermatogenesis of Danio rerio , 2015, Zygote.

[64]  Su Lu,et al.  Increased expression of prothymosin-α, independently or combined with TP53, correlates with poor prognosis in colorectal cancer. , 2014, International journal of clinical and experimental pathology.

[65]  R. Oko,et al.  First evidence of prothymosin alpha localization in the acrosome of mammalian male gametes , 2013, Journal of cellular physiology.

[66]  T. Myöhänen,et al.  Sequential Expression, Activity and Nuclear Localization of Prolyl Oligopeptidase Protein in the Developing Rat Brain , 2010, Developmental Neuroscience.

[67]  H. Vaudry,et al.  Prolyl endopeptidase mRNA expression in the central nervous system during rat development , 2010, Journal of Chemical Neuroanatomy.

[68]  Aldo Donizetti,et al.  Expression of prothymosin alpha in meiotic and post‐meiotic germ cells during the first wave of rat spermatogenesis , 2010, Journal of cellular physiology.

[69]  Organización Mundial de la Salud WHO laboratory manual for the examination and processing of human semen , 2010 .

[70]  F. Domínguez,et al.  Prothymosin α, a mammalian c-myc-regulated acidic nuclear protein, provokes the decondensation of human chromosomes in vitro , 2001, Cytogenetic and Genome Research.

[71]  A. Esquifino,et al.  Cadmium Effects on Hypothalamic-Pituitary-Testicular Axis in Male Rats , 2001, Experimental biology and medicine.

[72]  A. Esquifino,et al.  Pubertal and postpubertal cadmium exposure differentially affects the hypothalamic-pituitary-testicular axis function in the rat. , 2000, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[73]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.