Phosphoproteomic analysis of the adaption of epididymal epithelial cells to corticosterone challenge.
DNA damage
cellular signaling
corticosterone
epididymis
phosphoproteomics
proteomics
sperm maturation
stress response
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
04 Apr 2024
04 Apr 2024
Historique:
revised:
29
02
2024
received:
16
08
2023
accepted:
08
03
2024
medline:
5
4
2024
pubmed:
5
4
2024
entrez:
5
4
2024
Statut:
aheadofprint
Résumé
The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved. The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells), in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks. The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer, was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge. The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome (i.e., only 73 out of 4171 [∼1.8%] proteins displayed altered abundance). By contrast, ∼15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increase in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells. Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge, and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases.
Sections du résumé
BACKGROUND
BACKGROUND
The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved.
OBJECTIVE
OBJECTIVE
The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells), in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks.
MATERIALS AND METHODS
METHODS
The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer, was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge.
RESULTS
RESULTS
The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome (i.e., only 73 out of 4171 [∼1.8%] proteins displayed altered abundance). By contrast, ∼15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increase in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells.
CONCLUSIONS
CONCLUSIONS
Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge, and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Health and Medical Research Council (NHMRC)
ID : APP1147932
Organisme : National Health and Medical Research Council (NHMRC)
ID : APP1154837
Organisme : National Health and Medical Research Council (NHMRC)
ID : APP1173892
Organisme : ChadTough Foundation
Informations de copyright
© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.
Références
Bedford JM. Effects of duct ligation on the fertilizing ability of spermatozoa from different regions of the rabbit epididymis. J Exp Zool. 1967;166(2):271‐281. doi:10.1002/jez.1401660210
Orgebin‐Crist MC. Sperm maturation in rabbit epididymis. Nature. 1967;216(5117):816‐818. doi:10.1038/216816a0
Orgebin‐Crist MC. Maturation of spermatozoa in the rabbit epididymis: delayed fertilization in does inseminated with epididymal spermatozoa. J Reprod Fertil. 1968;16(1):29‐33. doi:10.1530/jrf.0.0160029
Orgebin‐Crist MC. Studies on the function of the epididymis. Biol Reprod. 1969;1(1):155‐175. doi:10.1095/biolreprod1.supplement_1.155. Suppl.
Bedford JM. Components of sperm maturation in the human epididymis. Adv Biosci. 1973;10:145‐155.
Bedford JM. Enigmas of mammalian gamete form and function. Biol Rev Camb Philos Soc. 2004;79(2):429‐460. doi:10.1017/s146479310300633x
Bedford JM. The epididymis re‐visited: a personal view. Asian J Androl. 2015;17(5):693‐698. doi:10.4103/1008‐682X.153297
Nixon B, Cafe SL, Eamens AL, et al. Molecular insights into the divergence and diversity of post‐testicular maturation strategies. Mol Cell Endocrinol. 2020;517:110955. doi:10.1016/j.mce.2020.110955
Bedford JM. Singular features of fertilization and their impact on the male reproductive system in eutherian mammals. Reproduction. 2014;147(2):R43‐52. doi:10.1530/REP‐13‐0436
Zhou W, De Iuliis GN, Dun MD, Nixon B. Characteristics of the epididymal luminal environment responsible for sperm maturation and storage. Front Endocrinol (Lausanne). 2018;9:59. doi:10.3389/fendo.2018.00059
Dacheux JL, Dacheux F, Druart X. Epididymal protein markers and fertility. Anim Reprod Sci. 2016;169:76‐87. doi:10.1016/j.anireprosci.2016.02.034
Dacheux JL, Dacheux F. New insights into epididymal function in relation to sperm maturation. Reproduction. 2014;147(2):R27‐42. doi:10.1530/REP‐13‐0420
Dacheux JL, Belleannee C, Guyonnet B, et al. The contribution of proteomics to understanding epididymal maturation of mammalian spermatozoa. Syst Biol Reprod Med. 2012;58(4):197‐210. doi:10.3109/19396368.2012.663233
Dacheux JL, Belleannee C, Jones R, et al. Mammalian epididymal proteome. Mol Cell Endocrinol. 2009;306(1‐2):45‐50. doi:10.1016/j.mce.2009.03.007
Aitken RJ, Nixon B, Lin M, Koppers AJ, Lee YH, Baker MA. Proteomic changes in mammalian spermatozoa during epididymal maturation. Asian J Androl. 2007;9(4):554‐564. doi:10.1111/j.1745‐7262.2007.00280.x
Dacheux JL, Gatti JL, Dacheux F. Contribution of epididymal secretory proteins for spermatozoa maturation. Microsc Res Tech. 2003;61(1):7‐17. doi:10.1002/jemt.10312
Skerget S, Rosenow MA, Petritis K, Karr TL. Sperm proteome maturation in the mouse epididymis. PLoS One. 2015;10(11):e0140650. doi:10.1371/journal.pone.0140650
Skerrett‐Byrne DA, Anderson AL, Bromfield EG, et al. Global profiling of the proteomic changes associated with the post‐testicular maturation of mouse spermatozoa. Cell Reports. 2022;41(7):111655.
Conine CC, Sun F, Song L, Rivera‐Perez JA, Rando OJ. Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice. Dev Cell. 2018;46(4):470‐480. doi:10.1016/j.devcel.2018.06.024. e3.
Conine CC, Sun F, Song L, Rivera‐Perez JA, Rando OJ. MicroRNAs absent in caput sperm are required for normal embryonic development. Dev Cell. 2019;50(1):7‐8. doi:10.1016/j.devcel.2019.06.007
Hutcheon K, McLaughlin EA, Stanger SJ, et al. Analysis of the small non‐protein‐coding RNA profile of mouse spermatozoa reveals specific enrichment of piRNAs within mature spermatozoa. RNA Biol. 2017;14(12):1776‐1790. doi:10.1080/15476286.2017.1356569
Nixon B, De Iuliis GN, Dun MD, Zhou W, Trigg NA, Eamens AL. Profiling of epididymal small non‐protein‐coding RNAs. Andrology. 2019;7(5):669‐680. doi:10.1111/andr.12640
Nixon B, Stanger SJ, Mihalas BP, et al. The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation. Biol Reprod. 2015;93(4):91. doi:10.1095/biolreprod.115.132209
Sharma U, Conine CC, Shea JM, et al. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science. 2016;351(6271):391‐396. doi:10.1126/science.aad6780
Sharma U, Sun F, Conine CC, et al. Small RNAs Are trafficked from the epididymis to developing mammalian sperm. Dev Cell. 2018;46(4):481‐494. doi:10.1016/j.devcel.2018.06.023. e6.
Nixon B, De Iuliis GN, Hart HM, et al. Proteomic profiling of mouse epididymosomes reveals their contributions to post‐testicular sperm maturation. Mol Cell Proteomics. 2019;18(1):S91‐s108. doi:10.1074/mcp.RA118.000946. Suppl.
Zhou W, Stanger SJ, Anderson AL, et al. Mechanisms of tethering and cargo transfer during epididymosome‐sperm interactions. BMC Biol. 2019;17(1):35. doi:10.1186/s12915‐019‐0653‐5
Reilly JN, McLaughlin EA, Stanger SJ, et al. Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome. Sci Rep. 2016;6:31794. doi:10.1038/srep31794
Trigg NA, Skerrett‐Byrne DA, Xavier MJ, et al. Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non‐coding RNA profile and dysregulate embryo development. Cell Rep. 2021;37(1):109787. doi:10.1016/j.celrep.2021.109787
Yin X, Anwar A, Wang Y, Hu H, Liang G, Zhang C. Paternal environmental exposure‐induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases. Front Med. 2022;16(2):176‐184. doi:10.1007/s11684‐021‐0885‐y
Trigg NA, Eamens AL, Nixon B. The contribution of epididymosomes to the sperm small RNA profile. Reproduction. 2019;157(6):R209‐r223. doi:10.1530/rep‐18‐0480
Nätt D, Öst A. Male reproductive health and intergenerational metabolic responses from a small RNA perspective. J Intern Med. 2020;288(3):305‐320. doi:10.1111/joim.13096
Ly L, Chan D, Trasler JM. Developmental windows of susceptibility for epigenetic inheritance through the male germline. Semin Cell Dev Biol. 2015;43:96‐105. doi:10.1016/j.semcdb.2015.07.006
Klastrup LK, Bak ST, Nielsen AL. The influence of paternal diet on sncRNA‐mediated epigenetic inheritance. Mol Genet Genomics. 2019;294(1):1‐11. doi:10.1007/s00438‐018‐1492‐8
Short AK, Fennell KA, Perreau VM, et al. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Transl Psychiatry. 2016;6(6):e837. doi:10.1038/tp.2016.109
Rawat A, Guo J, Renoir T, Pang TY, Hannan AJ. Hypersensitivity to sertraline in the absence of hippocampal 5‐HT1AR and 5‐HTT gene expression changes following paternal corticosterone treatment. Environ Epigenet. 2018;4(2):dvy015. doi:10.1093/eep/dvy015
Ihne JL, Fitzgerald PJ, Hefner KR, Holmes A. Pharmacological modulation of stress‐induced behavioral changes in the light/dark exploration test in male C57BL/6J mice. Neuropharmacology. 2012;62(1):464‐473. doi:10.1016/j.neuropharm.2011.08.045
Mozhui K, Karlsson RM, Kash TL, et al. Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate‐mediated neuronal excitability. J Neurosci. 2010;30(15):5357‐5367. doi:10.1523/JNEUROSCI.5017‐09.2010
Wu L, Lu Y, Jiao Y, et al. Paternal psychological stress reprograms hepatic gluconeogenesis in offspring. Cell Metab. 2016;23(4):735‐743. doi:10.1016/j.cmet.2016.01.014
Motavalli R, Majidi T, Pourlak T, et al. The clinical significance of the glucocorticoid receptors: genetics and epigenetics. J Steroid Biochem Mol Biol. 2021;213:105952. doi:10.1016/j.jsbmb.2021.105952
Silva EJ, Queiroz DB, Rodrigues A, Honda L, Avellar MC. Innate immunity and glucocorticoids: potential regulatory mechanisms in epididymal biology. J Androl. 2011;32(6):614‐624. doi:10.2164/jandrol.111.013565
Silva EJ, Queiroz DB, Honda L, Avellar MC. Glucocorticoid receptor in the rat epididymis: expression, cellular distribution and regulation by steroid hormones. Mol Cell Endocrinol. 2010;325(1‐2):64‐77. doi:10.1016/j.mce.2010.05.013
Schultz R, Isola J, Parvinen M, et al. Localization of the glucocorticoid receptor in testis and accessory sexual organs of male rat. Mol Cell Endocrinol. 1993;95(1‐2):115‐120. doi:10.1016/0303‐7207(93)90036‐j
Sipila P, Shariatmadari R, Huhtaniemi IT, Poutanen M. Immortalization of epididymal epithelium in transgenic mice expressing simian virus 40 T antigen: characterization of cell lines and regulation of the polyoma enhancer activator 3. Endocrinology. 2004;145(1):437‐446. doi:10.1210/en.2003‐0831
Nixon B, Stanger SJ, Mihalas BP, et al. Next generation sequencing analysis reveals segmental patterns of microRNA expression in mouse epididymal epithelial cells. PLoS One. 2015;10(8):e0135605. doi:10.1371/journal.pone.0135605
Zhou W, Sipila P, De Iuliis GN, Dun MD, Nixon B. Analysis of epididymal protein synthesis and secretion. J Vis Exp. 2018;138:e58308. doi:10.3791/58308
Fennell KA, Busby RGG, Li S, et al. Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety. Sci Rep. 2020;10(1):16050. doi:10.1038/s41598‐020‐72560‐z
Owonikoko TK, Zhang G, Lallani SB, et al. Evaluation of preclinical efficacy of everolimus and pasireotide in thyroid cancer cell lines and xenograft models. PLoS One. 2019;14(2):e0206309. doi:10.1371/journal.pone.0206309
Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680‐685.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 1979;76(9):4350‐4354.
Trigg NA, Skerrett‐Byrne DA, Xavier MJ, et al. Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non‐coding RNA profile and dysregulate embryo development. Cell Rep. 2021;37:109787.
Schmittgen TD, Livak KJ. Analyzing real‐time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101‐1108. doi:10.1038/nprot.2008.73
Schjenken JE, Moldenhauer LM, Zhang B, et al. MicroRNA miR‐155 is required for expansion of regulatory T cells to mediate robust pregnancy tolerance in mice. Mucosal Immunol. 2020;13(4):609‐625. doi:10.1038/s41385‐020‐0255‐0
Humphrey SJ, Karayel O, James DE, Mann M. High‐throughput and high‐sensitivity phosphoproteomics with the EasyPhos platform. Nat Protoc. 2018;13(9):1897‐1916. doi:10.1038/s41596‐018‐0014‐9
Smyth SP, Nixon B, Anderson AL, et al. Elucidation of the protein composition of mouse seminal vesicle fluid. Proteomics. 2022;22(9):e2100227. doi:10.1002/pmic.202100227
Rappsilber J, Mann M, Ishihama Y. Protocol for micro‐purification, enrichment, pre‐fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007;2(8):1896‐1906. doi:10.1038/nprot.2007.261
Degryse S, de Bock CE, Demeyer S, et al. Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T‐cell acute lymphoblastic leukemia. Leukemia. 2018;32(3):788‐800. doi:10.1038/leu.2017.276
Murray HC, Enjeti AK, Kahl RGS, et al. Quantitative phosphoproteomics uncovers synergy between DNA‐PK and FLT3 inhibitors in acute myeloid leukaemia. Leukemia. 2021;35(6):1782‐1787. doi:10.1038/s41375‐020‐01050‐y
Nixon B, Johnston SD, Skerrett‐Byrne DA, et al. Modification of crocodile spermatozoa refutes the tenet that post‐testicular sperm maturation is restricted to mammals. Mol Cell Proteomics. 2019;18(1):S58‐s76. doi:10.1074/mcp.RA118.000904. Suppl.
Skerrett‐Byrne DA, Bromfield EG, Murray HC, et al. Time‐resolved proteomic profiling of cigarette smoke‐induced experimental chronic obstructive pulmonary disease. Respirology. 2021;26:960‐973. doi:10.1111/resp.14111
Skerrett‐Byrne DA, Trigg NA, Bromfield EG, et al. Proteomic dissection of the impact of environmental exposures on mouse seminal vesicle function. Mol Cell Proteomics. 2021;20:100107. doi:10.1016/j.mcpro.2021.100107
Taus T, Köcher T, Pichler P, et al. Universal and confident phosphorylation site localization using phosphoRS. J Proteome Res. 2011;10(12):5354‐5362. doi:10.1021/pr200611n
Tyanova S, Temu T, Sinitcyn P, et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods. 2016;13(9):731‐740. doi:10.1038/nmeth.3901
Skerrett‐Byrne DA, Anderson AL, Hulse L, et al. Proteomic analysis of koala (Phascolarctos cinereus) spermatozoa and prostatic bodies. Proteomics. 2021;21(19):e2100067. doi:10.1002/pmic.202100067
Zhang M, Chiozzi RZ, Skerrett‐Byrne DA, et al. High resolution proteomic analysis of subcellular fractionated boar spermatozoa provides comprehensive insights into perinuclear theca‐residing proteins. Front Cell Dev Biol. 2022;10:836208. doi:10.3389/fcell.2022.836208
Skerrett‐Byrne DA, Nixon B, Bromfield EG, et al. Transcriptomic analysis of the seminal vesicle response to the reproductive toxicant acrylamide. BMC Genomics. 2021;22(1):728. doi:10.1186/s12864‐021‐07951‐1
Krämer A, Green J, Pollard J Jr, Tugendreich S. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics. 2014;30(4):523‐530. doi:10.1093/bioinformatics/btt703
Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127‐D131.
Liu W, Wang X. Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biol. 2019;20:1‐10.
Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2015;43:D512‐520. doi:10.1093/nar/gku1267. Database issue.
Johnston DS, Jelinsky SA, Bang HJ, et al. The mouse epididymal transcriptome: transcriptional profiling of segmental gene expression in the epididymis. Biol Reprod. 2005;73(3):404‐413. doi:10.1095/biolreprod.105.039719
Trigg NA, Stanger SJ, Zhou W, et al. A novel role for milk fat globule‐EGF factor 8 protein (MFGE8) in the mediation of mouse sperm‐extracellular vesicle interactions. Proteomics. 2021;21(13‐14):e2000079. doi:10.1002/pmic.202000079
Mulhall JE, Trigg NA, Bernstein IR, et al. Immortalized mouse caput epididymal epithelial (mECap18) cell line recapitulates the in-vivo environment. Proteomics. 2023:e2300253. doi:10.1002/pmic.202300253
Cortez D, Wang Y, Qin J, Elledge SJ. Requirement of ATM‐dependent phosphorylation of brca1 in the DNA damage response to double‐strand breaks. Science. 1999;286(5442):1162‐1166. doi:10.1126/science.286.5442.1162
Pearl LH, Schierz AC, Ward SE, Al‐Lazikani B, Pearl FM. Therapeutic opportunities within the DNA damage response. Nat Rev Cancer. 2015;15(3):166‐180. doi:10.1038/nrc3891
Wang H, Kim NH. CDK2 is required for the DNA damage response during porcine early embryonic development. Biol Reprod. 2016;95(2):31. doi:10.1095/biolreprod.116.140244
Liberal V, Martinsson‐Ahlzén HS, Liberal J, et al. Cyclin‐dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteins. Proc Natl Acad Sci USA. 2012;109(8):2754‐2759. doi:10.1073/pnas.1102434108
Phong MS, Van Horn RD, Li S, Tucker‐Kellogg G, Surana U, Ye XS. p38 mitogen‐activated protein kinase promotes cell survival in response to DNA damage but is not required for the G(2) DNA damage checkpoint in human cancer cells. Mol Cell Biol. 2010;30(15):3816‐3826. doi:10.1128/mcb.00949‐09
Liu Q, Turner KM, Alfred Yung WK, Chen K, Zhang W. Role of AKT signaling in DNA repair and clinical response to cancer therapy. Neuro Oncol. 2014;16(10):1313‐1323. doi:10.1093/neuonc/nou058
Ma Y, Vassetzky Y, Dokudovskaya S. mTORC1 pathway in DNA damage response. Biochim Biophys Acta Mol Cell Res. 2018;1865(9):1293‐1311. doi:10.1016/j.bbamcr.2018.06.011
Findlay IJ, De Iuliis GN, Duchatel RJ, et al. Pharmaco‐proteogenomic profiling of pediatric diffuse midline glioma to inform future treatment strategies. Oncogene. 2022;41(4):461‐475. doi:10.1038/s41388‐021‐02102‐y
Chan JC, Nugent BM, Bale TL. Parental advisory: maternal and paternal stress can impact offspring neurodevelopment. Biol Psychiatry. 2018;83(10):886‐894. doi:10.1016/j.biopsych.2017.10.005
Chen Q, Yan W, Duan E. Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet. 2016;17(12):733‐743. doi:10.1038/nrg.2016.106
Pang TYC, Short AK, Bredy TW, Hannan AJ. Transgenerational paternal transmission of acquired traits: stress‐induced modification of the sperm regulatory transcriptome and offspring phenotypes. Curr Opin Behav Sci. 2017;14:140‐147. doi:10.1016/j.cobeha.2017.02.007
Sharma U. Paternal contributions to offspring health: role of sperm small RNAs in intergenerational transmission of epigenetic information. Front Cell Dev Biol. 2019;7:215. doi:10.3389/fcell.2019.00215
Short AK, Yeshurun S, Powell R, et al. Exercise alters mouse sperm small noncoding RNAs and induces a transgenerational modification of male offspring conditioned fear and anxiety. Transl Psychiatry. 2017;7(5):e1114. doi:10.1038/tp.2017.82
Auchus RJ. Steroid 17‐hydroxylase and 17,20‐lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol. 2017;165:71‐78. doi:10.1016/j.jsbmb.2016.02.002. Pt A.
Oyola MG, Handa RJ. Hypothalamic‐pituitary‐adrenal and hypothalamic‐pituitary‐gonadal axes: sex differences in regulation of stress responsivity. Stress. 2017;20(5):476‐494. doi:10.1080/10253890.2017.1369523
Cooke PS, Holsberger DR, Witorsch RJ, et al. Thyroid hormone, glucocorticoids, and prolactin at the nexus of physiology, reproduction, and toxicology. Toxicol Appl Pharmacol. 2004;194(3):309‐335. doi:10.1016/j.taap.2003.09.016
Zhou J, Cidlowski JA. The human glucocorticoid receptor: one gene, multiple proteins and diverse responses. Steroids. 2005;70(5‐7):407‐417. doi:10.1016/j.steroids.2005.02.006
Kumar R, Thompson EB. Gene regulation by the glucocorticoid receptor: structure:function relationship. J Steroid Biochem Mol Biol. 2005;94(5):383‐394. doi:10.1016/j.jsbmb.2004.12.046
Weber MA, Groos S, Hopfl U, Spielmann M, Aumuller G, Konrad L. Glucocorticoid receptor distribution in rat testis during postnatal development and effects of dexamethasone on immature peritubular cells in vitro. Andrologia. 2000;32(1):23‐30.
Lescoat G, Lescoat D, Garnier DH. Influence of adrenalectomy on maturation of gonadotrophin function in the male rat. J Endocrinol. 1982;95(1):1‐6. doi:10.1677/joe.0.0950001
Gao HB, Ge RS, Lakshmi V, Marandici A, Hardy MP. Hormonal regulation of oxidative and reductive activities of 11 beta‐hydroxysteroid dehydrogenase in rat Leydig cells. Endocrinology. 1997;138(1):156‐161. doi:10.1210/endo.138.1.4837
Au CL, Ngai HK, Yeung CH, Wong PY. Effect of adrenalectomy and hormone replacement on sodium and water transport in the perfused rat cauda epididymidis. J Endocrinol. 1978;77(2):265‐266. doi:10.1677/joe.0.0770265
Garcia‐Diaz EC, Gomez‐Quiroz LE, Arenas‐Rios E, Aragon‐Martinez A, Ibarra‐Arias JA, del Socorro IR‐MM. Oxidative status in testis and epididymal sperm parameters after acute and chronic stress by cold‐water immersion in the adult rat. Syst Biol Reprod Med. 2015;61(3):150‐160. doi:10.3109/19396368.2015.1008071
Nair N, Bedwal RS, Mathur RS. Zinc, copper and hydrolytic enzymes in epididymis of hydrocortisone treated rat. Indian J Exp Biol. 1998;36(1):22‐33.
Nair N, Bedwal RS, Mathur RS. Effect of adrenalectomy on rat epididymidis. Asian J Androl. 2002;4(4):273‐279.
Chan JC, Morgan CP, Adrian Leu N, et al. Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment. Nat Commun. 2020;11(1):1499. doi:10.1038/s41467‐020‐15305‐w
Chan JC, Nugent BM, Morrison KE, et al. Epididymal glucocorticoid receptors promote intergenerational transmission of paternal stress. bioRxiv. 2018:321976. doi:10.1101/321976
Chan JC, Morgan CP, Adrian Leu N, et al. Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment. Nat Commun. 2020;11(1):1499. doi:10.1038/s41467‐020‐15305‐w
Harris AZ, Atsak P, Bretton ZH, et al. A novel method for chronic social defeat stress in female mice. Neuropsychopharmacology. 2018;43(6):1276‐1283. doi:10.1038/npp.2017.259
Nakatake Y, Furuie H, Yamada M, et al. The effects of emotional stress are not identical to those of physical stress in mouse model of social defeat stress. Neurosci Res. 2020;158:56‐63. doi:10.1016/j.neures.2019.10.008
Menard C, Pfau ML, Hodes GE, et al. Social stress induces neurovascular pathology promoting depression. Nat Neurosci. 2017;20(12):1752‐1760. doi:10.1038/s41593‐017‐0010‐3
Zhou W, De Iuliis GN, Turner AP, et al. Developmental expression of the dynamin family of mechanoenzymes in the mouse epididymis. Biol Reprod. 2017;96(1):159‐173. doi:10.1095/biolreprod.116.145433
Katen AL, Sipila P, Mitchell LA, Stanger SJ, Nixon B, Roman SD. Epididymal CYP2E1 plays a critical role in acrylamide‐induced DNA damage in spermatozoa and paternally mediated embryonic resorptions. Biol Reprod. 2017;96(4):921‐935. doi:10.1093/biolre/iox021
Burnstein KL, Bellingham DL, Jewell CM, Powell‐Oliver FE, Cidlowski JA. Autoregulation of glucocorticoid receptor gene expression. Steroids. 1991;56(2):52‐58. doi:10.1016/0039‐128x(91)90124‐e
Zang H, Mathew RO, Cui T. The dark side of Nrf2 in the heart. Front Physiol. 2020;11:722. doi:10.3389/fphys.2020.00722
Nguyen T, Nioi P, Pickett CB. The Nrf2‐antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009;284(20):13291‐13295. doi:10.1074/jbc.R900010200
Krieger KL, Hu WF, Ripperger T, Woods NT. Functional impacts of the BRCA1‐mTORC2 interaction in breast cancer. Int J Mol Sci. 2019;20(23):5876. doi:10.3390/ijms20235876
di Fagagna FDA. A direct role for small non‐coding RNAs in DNA damage response. Trends Cell Biol. 2014;24(3):171‐178.
Wei W, Ba Z, Gao M, et al. A role for small RNAs in DNA double‐strand break repair. Cell. 2012;149(1):101‐112. doi:10.1016/j.cell.2012.03.002
Zhang X, Yan C, Zhan X, Li L, Lei J, Shi Y. Structure of the human activated spliceosome in three conformational states. Cell Res. 2018;28(3):307‐322. doi:10.1038/cr.2018.14
Yu B, Bi L, Zheng B, et al. The FHA domain proteins DAWDLE in Arabidopsis and SNIP1 in humans act in small RNA biogenesis. Proc Natl Acad Sci USA. 2008;105(29):10073‐10078. doi:10.1073/pnas.0804218105
Nawaz A, Shilikbay T, Skariah G, Ceman S. Unwinding the roles of RNA helicase MOV10. Wiley Interdiscip Rev RNA. 2021;13:e1682. doi:10.1002/wrna.1682
Frost RJ, Hamra FK, Richardson JA, Qi X, Bassel‐Duby R, Olson EN. MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi‐interacting RNAs. Proc Natl Acad Sci USA. 2010;107(26):11847‐11852. doi:10.1073/pnas.1007158107
Treiber T, Treiber N, Plessmann U, et al. A compendium of RNA‐binding proteins that regulate microRNA biogenesis. Mol Cell. 2017;66(2):270‐284. doi:10.1016/j.molcel.2017.03.014. e13.
Perez‐Riverol Y, Csordas A, Bai J, et al. The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res. 2019;47(D1):D442‐d450. doi:10.1093/nar/gky1106