In the last two decades, a school of thought emerged that perceives male reproductive health, testicular function, and sperm output as a sentry for general, somatic health. Large-scale epidemiologic studies have already linked the reduced sperm count to increased risk of chronic somatic disease (e.g., cancer, cardiovascular, neurological and bone diseases), yet most of these studies have not taken full advantage of advanced andrological analysis. Altered proteostasis, i.e., the disbalance between protein synthesis and turnover, is a common denominator of many diseases, including but not limited to cancer and neurodegenerative diseases. This chapter introduces the concept of cellular proteostasis as a measure of sperm structural and functional integrity and an endpoint of varied impacts on spermiogenesis and sperm maturation, including heritability, general health, lifestyle, and occupational and environmental reprotoxic exposure. Special consideration is given to small molecule protein modifiers, sperm-binding seminal plasma proteins, zinc-interacting proteins, and redox proteins responsible for the maintenance of protein structure and the protection of spermatozoa from oxidative damage. While the main focus is on human male infertility, serious consideration is given to relevant animal models, and in particular to male food animals with extensive records of fertility from artificial insemination services. Altogether, the proteostatic biomarker discovery and validation studies set the stage for the integration of proteomics of sperm proteostasis with genomic and high throughput phenomic approaches to benefit both human and animal reproductive medicine.

• Keywords
• Biomarker, Infertility, Omics, Proteasome, Proteostasis, Seminal plasma, Sperm, Thioredoxin, Ubiquitin,
• MeSH
• Fertility * physiology   MeSH
• Proteostasis * physiology   MeSH
• Humans MeSH
• Infertility, Male * metabolism   genetics   pathology   physiopathology   MeSH
• Spermatogenesis * MeSH
• Spermatozoa * metabolism   pathology   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.

• Keywords
• 17α-Ethynylestradiol, DNA methylation, EE2, Endocrine disruptors, Histone-to-protamine exchange, Post-translational modifications, Sperm, Testis, Transgenerational study,
• MeSH
• Endocrine Disruptors pharmacology   toxicity   MeSH
• Epigenesis, Genetic * drug effects   MeSH
• Ethinyl Estradiol * pharmacology   MeSH
• Histones * metabolism   MeSH
• Mice MeSH
• Protein Processing, Post-Translational drug effects   MeSH
• Protamines * metabolism   genetics   MeSH
• Spermatogenesis * drug effects   genetics   MeSH
• Spermatozoa drug effects   metabolism   MeSH
• Testis * drug effects   metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Endocrine Disruptors MeSH
• Ethinyl Estradiol * MeSH
• Histones * MeSH
• Protamines * MeSH