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

Estrogens are steroid hormones that affect a wide range of physiological functions. The effect of estrogens on male reproductive tissues and sperm cells through specific receptors is essential for sperm development, maturation, and function. Although estrogen receptors (ERs) have been studied in several mammalian species, including humans, they have not yet been described in bull spermatozoa and reproductive tissues. In this study, we analyzed the presence of all types of ERs (ESR1, ESR2, and GPER1) in bull testicular and epididymal tissues and epididymal and ejaculated spermatozoa, and we characterize them here for the first time. We observed different localizations of each type of ER in the sperm head by immunofluorescent microscopy. Additionally, using a selected polyclonal antibody, we found that each type of ER in bull sperm extracts had two isoforms with different molecular masses. The detailed detection of ERs is a prerequisite not only for understanding the effect of estrogen on all reproductive events but also for further studying the negative effect of environmental estrogens (endocrine disruptors) on processes that lead to fertilization.

• Keywords
• bovine, epididymis, plasma membrane, reproduction, steroid hormones, testes,
• MeSH
• Epididymis metabolism   MeSH
• Receptors, Estrogen metabolism   MeSH
• Receptors, G-Protein-Coupled metabolism   MeSH
• Reproduction * MeSH
• Cattle metabolism   MeSH
• Spermatozoa metabolism   MeSH
• Testis metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Cattle metabolism   MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Receptors, Estrogen MeSH
• Receptors, G-Protein-Coupled MeSH

17β-estradiol (estradiol) is a natural estrogen regulating reproduction including sperm and egg development, sperm maturation-called capacitation-and sperm⁻egg communication. High doses can increase germ cell apoptosis and decrease sperm count. Our aim was to answer the biological relevance of estradiol in sperm capacitation and its effect on motility and acrosome reaction to quantify its interaction with estrogen receptors and propose a model of estradiol action during capacitation using kinetic analysis. Estradiol increased protein tyrosine phosphorylation, elevated rate of spontaneous acrosome reaction, and altered motility parameters measured Hamilton-Thorne Computer Assisted Semen Analyzer (CASA) in capacitating sperm. To monitor time and concentration dependent binding dynamics of extracellular estradiol, high-performance liquid chromatography with tandem mass spectrometry was used to measure sperm response and data was subjected to kinetic analysis. The kinetic model of estradiol action during sperm maturation shows that estradiol adsorption onto a plasma membrane surface is controlled by Langmuir isotherm. After, when estradiol passes into the cytoplasm, it forms an unstable adduct with cytoplasmic receptors, which display a signalling autocatalytic pattern. This autocatalytic reaction suggests crosstalk between receptor and non-receptor pathways utilized by sperm prior to fertilization.

• Keywords
• 17β-estradiol, CASA, HPLC MS/MS, acrosome reaction, autocatalysis, capacitation, kinetics, sperm,
• MeSH
• Acrosome Reaction drug effects   MeSH
• Estradiol metabolism   pharmacology   MeSH
• Sperm Capacitation drug effects   physiology   MeSH
• Kinetics MeSH
• Sperm Motility drug effects   MeSH
• Mice, Inbred C57BL MeSH
• Progesterone pharmacology   MeSH
• Signal Transduction * MeSH
• Semen drug effects   metabolism   MeSH
• Chromatography, High Pressure Liquid MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Estradiol MeSH
• Progesterone MeSH

The crucial role that oestrogens play in male reproduction has been generally accepted; however, the exact mechanism of their action is not entirely clear and there is still much more to be clarified. The oestrogen response is mediated through oestrogen receptors, as well as classical oestrogen receptors' variants, and their specific co-expression plays a critical role. The importance of oestrogen signalling in male fertility is indicated by the adverse effects of selected oestrogen-like compounds, and their interaction with oestrogen receptors was proven to cause pathologies. The aims of this review are to summarise the current knowledge on oestrogen signalling during spermatogenesis and sperm maturation and discuss the available information on oestrogen receptors and their splice variants. An overview is given of species-specific differences including in humans, along with a detailed summary of the methodology outcome, including all the genetically manipulated models available to date. This review provides coherent information on the recently discovered mechanisms of oestrogens' and oestrogen receptors' effects and action in both testicular somatic and germ cells, as well as in mature sperm, available for mammals, including humans.

• Keywords
• humans, mice, oestrogen receptors, oestrogen-like compounds, oestrogens, pigs, rats, signalling, sperm, testes,
• MeSH
• Aromatase deficiency   genetics   MeSH
• Estrogens pharmacology   MeSH
• Humans MeSH
• Receptors, Estrogen metabolism   MeSH
• Signal Transduction MeSH
• Spermatogenesis drug effects   MeSH
• Testis drug effects   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Aromatase MeSH
• Estrogens MeSH
• Receptors, Estrogen MeSH