{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:12:06Z","timestamp":1790806326038,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["GENIDOV: ANR-09-GENM-009"],"award-info":[{"award-number":["GENIDOV: ANR-09-GENM-009"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ARGONADS: ANR-13-BSV2-0017"],"award-info":[{"award-number":["ARGONADS: ANR-13-BSV2-0017"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ARDIGERM: ANR-2020-CE14-0022"],"award-info":[{"award-number":["ARDIGERM: ANR-2020-CE14-0022"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["CELPHEDIA France, 2017"],"award-info":[{"award-number":["CELPHEDIA France, 2017"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CELPHEDIA infrastructure","award":["GENIDOV: ANR-09-GENM-009"],"award-info":[{"award-number":["GENIDOV: ANR-09-GENM-009"]}]},{"name":"CELPHEDIA infrastructure","award":["ARGONADS: ANR-13-BSV2-0017"],"award-info":[{"award-number":["ARGONADS: ANR-13-BSV2-0017"]}]},{"name":"CELPHEDIA infrastructure","award":["ARDIGERM: ANR-2020-CE14-0022"],"award-info":[{"award-number":["ARDIGERM: ANR-2020-CE14-0022"]}]},{"name":"CELPHEDIA infrastructure","award":["CELPHEDIA France, 2017"],"award-info":[{"award-number":["CELPHEDIA France, 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Estrogens are steroid hormones produced by the aromatization of androgens by the aromatase enzyme, encoded by the CYP19A1 gene. Although generally referred to as \u201cfemale sex hormones\u201d, estrogen is also produced in the adult testes of many mammals, including humans. To better understand the function of estrogens in the male, we used the rabbit model which is an important biomedical model. First, the expression of CYP19A1 transcripts was localized mainly in meiotic germ cells. Thus, testicular estrogen appears to be produced inside the seminiferous tubules. Next, the cells expressing ESR1 and ESR2 were identified, showing that estrogens could exert their function on post-meiotic germ cells in the tubules and play a role during sperm maturation, since ESR1 and ESR2 were detected in the cauda epididymis. Then, CRISPR\/Cas9 CYP19A1\u2212\/\u2212 genetically modified rabbits were analyzed. CYP19A1\u2212\/\u2212 males showed decreased fertility with lower sperm count associated with hypo-spermatogenesis and lower spermatid number. Germ\/sperm cell DNA methylation was unchanged, while sperm parameters were affected as CYP19A1\u2212\/\u2212 males exhibited reduced sperm motility associated with increased flagellar defects. In conclusion, testicular estrogens could be involved in the spermatocyte\u2013spermatid transition in the testis, and in the acquisition of sperm motility in the epididymis.<\/jats:p>","DOI":"10.3390\/genes13112070","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:34:52Z","timestamp":1667961292000},"page":"2070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Absence of Testicular Estrogen Leads to Defects in Spermatogenesis and Increased Semen Abnormalities in Male Rabbits"],"prefix":"10.3390","volume":"13","author":[{"given":"Aur\u00e9lie","family":"Dewaele","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Dujardin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolaine","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Albina","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Jammes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-1214","authenticated-orcid":false,"given":"Frank","family":"Giton","sequence":"additional","affiliation":[{"name":"APHP, P\u00f4le Biologie-Pathologie Henri Mondor, 94040 Cr\u00e9teil, France"},{"name":"INSERM IMRB U955, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9251-9077","authenticated-orcid":false,"given":"Eli","family":"Sellem","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Jolivet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pailhoux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5826-619X","authenticated-orcid":false,"given":"Ma\u00eblle","family":"Pannetier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, INRAE, BREED, 78350 Jouy-en-Josas, France"},{"name":"\u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, BREED, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/(SICI)1098-2795(199910)54:2<154::AID-MRD7>3.0.CO;2-5","article-title":"Involvement of Estrogens in the Process of Sex Differentiation in Two Fish Species: The Rainbow Trout (Oncorhynchus Mykiss) and a Tilapia (Oreochromis Niloticus)","volume":"54","author":"Guiguen","year":"1999","journal-title":"Mol. Reprod. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s000180050342","article-title":"Temperature-Dependent Sex Determination and Gonadal Differentiation in Reptiles","volume":"55","author":"Pieau","year":"1999","journal-title":"Cell Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.1734525","article-title":"Aromatase Enzyme Activity and Sex Determination in Chickens","volume":"255","author":"Elbrecht","year":"1992","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5264","DOI":"10.1073\/pnas.93.11.5264","article-title":"Functional Testicular Tissue Does Not Masculinize Development of the Zebra Finch Song System","volume":"93","author":"Wade","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/jez.1123","article-title":"Sex Reversal and Aromatase in Chicken","volume":"290","author":"Vaillant","year":"2001","journal-title":"J. Exp. Zool."},{"key":"ref_6","first-page":"38","article-title":"A New Look at the Mechanisms Controlling Sex Differentiation in Mammals","volume":"130","author":"Jost","year":"1972","journal-title":"Johns Hopkins Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.diff.2020.11.004","article-title":"Estrogens and Development of the Rete Testis, Efferent Ductules, Epididymis and Vas Deferens","volume":"118","author":"Hess","year":"2021","journal-title":"Differentiation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jsbmb.2005.04.020","article-title":"Aromatase in Testis: Expression and Role in Male Reproduction","volume":"95","author":"Lambard","year":"2005","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1095\/biolreprod58.4.919","article-title":"Expression and Immunolocalization of Functional Cytochrome P450 Aromatase in Mature Rat Testicular Cells1","volume":"58","author":"Levallet","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_10","first-page":"51","article-title":"Cytochrome P450 Aromatase in the Testis of Immature and Mature Pigs","volume":"1","author":"Fraczek","year":"2001","journal-title":"Reprod. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1177\/002215540305100306","article-title":"Immunolocalization of Aromatase in Stallion Leydig Cells and Seminiferous Tubules","volume":"51","author":"Sipahutar","year":"2003","journal-title":"J. Histochem. Cytochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1210\/jcem-42-6-1081","article-title":"Intratesticular Site of Aromatization in the Human","volume":"42","author":"Payne","year":"1976","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/0022-4731(86)90385-7","article-title":"Rat Testis 17\u03b2-Estradiol: Identification by Gas Chromatography-Mass Spectrometry and Age Related Cellular Distribution","volume":"24","author":"Papadopoulos","year":"1986","journal-title":"J. Steroid Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1210\/endo.132.3.8440194","article-title":"Germ Cells of the Mouse Testis Express P450 Aromatase","volume":"132","author":"Nitta","year":"1993","journal-title":"Endocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1677\/jme.0.0320279","article-title":"Human Immature Germ Cells and Ejaculated Spermatozoa Contain Aromatase and Oestrogen Receptors","volume":"32","author":"Lambard","year":"2004","journal-title":"J. Mol. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1477-7827-5-23","article-title":"Cytochrome P450arom, Androgen and Estrogen Receptors in Pig Sperm","volume":"5","author":"Rago","year":"2007","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dostalova, P., Zatecka, E., and Dvorakova-Hortova, K. (2017). Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen Receptors in Male Reproduction. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050904"},{"key":"ref_18","first-page":"4835","article-title":"Immunocytochemical Localization of Estrogen Receptors Alpha and Beta in the Human Reproductive Organs","volume":"85","author":"Pelletier","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00418-014-1216-z","article-title":"Expression Pattern of Estrogen Receptors \u03b1 and \u03b2 and G-Protein-Coupled Estrogen Receptor 1 in the Human Testis","volume":"142","author":"Fietz","year":"2014","journal-title":"Histochem. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3109\/19396360902855733","article-title":"Estrogen Receptors Alpha and Beta in Human Testis: Both Isoforms Are Expressed","volume":"55","author":"Cavaco","year":"2009","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S1043-2760(03)00028-6","article-title":"Isoform\/Variant MRNAs for Sex Steroid Hormone Receptors in Humans","volume":"14","author":"Hirata","year":"2003","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mce.2016.03.024","article-title":"Differential Roles of Estrogen Receptors, ESR1 and ESR2, in Adult Rat Spermatogenesis","volume":"428","author":"Dumasia","year":"2016","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1080\/15592294.2017.1382786","article-title":"Estrogen, through Estrogen Receptor 1, Regulates Histone Modifications and Chromatin Remodeling during Spermatogenesis in Adult Rats","volume":"12","author":"Dumasia","year":"2017","journal-title":"Epigenetics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1080\/15592294.2017.1309489","article-title":"Estrogen Signaling, through Estrogen Receptor \u03b2, Regulates DNA Methylation and Its Machinery in Male Germ Line in Adult Rats","volume":"12","author":"Dumasia","year":"2017","journal-title":"Epigenetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15677","DOI":"10.1073\/pnas.95.26.15677","article-title":"Generation and Reproductive Phenotypes of Mice Lacking Estrogen Receptor Beta","volume":"95","author":"Krege","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1073\/pnas.0712029105","article-title":"Sterility and Absence of Histopathological Defects in Nonreproductive Organs of a Mouse ERbeta-Null Mutant","volume":"105","author":"Antal","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1095\/biolreprod.108.071175","article-title":"GPR30 Does Not Mediate Estrogenic Responses in Reproductive Organs in Mice","volume":"80","author":"Otto","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1210\/endo.137.11.8895349","article-title":"Targeted Disruption of the Estrogen Receptor Gene in Male Mice Causes Alteration of Spermatogenesis and Infertility","volume":"137","author":"Eddy","year":"1996","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1095\/biolreprod.109.079889","article-title":"Absence of Estrogen Receptor Alpha Leads to Physiological Alterations in the Mouse Epididymis and Consequent Defects in Sperm Function","volume":"82","author":"Joseph","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1095\/biolreprod.109.080366","article-title":"Epididymal Hypo-Osmolality Induces Abnormal Sperm Morphology and Function in the Estrogen Receptor Alpha Knockout Mouse","volume":"82","author":"Joseph","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7986","DOI":"10.1073\/pnas.96.14.7986","article-title":"Impairment of Spermatogenesis in Mice Lacking a Functional Aromatase (Cyp 19) Gene","volume":"96","author":"Robertson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/j.1939-4640.2001.tb02587.x","article-title":"Characterization of the Fertility of Male Aromatase Knockout Mice","volume":"22","author":"Robertson","year":"2001","journal-title":"J. Androl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"240","DOI":"10.4161\/spmg.1.3.18037","article-title":"Teasing out the Role of Aromatase in the Healthy and Diseased Testis","volume":"1","author":"Haverfield","year":"2011","journal-title":"Spermatogenesis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1210\/jc.2002-020498","article-title":"Impact of Estrogen Replacement Therapy in a Male with Congenital Aromatase Deficiency Caused by a Novel Mutation in the CYP19 Gene","volume":"87","author":"Herrmann","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1056\/NEJM199707103370204","article-title":"Effect of Testosterone and Estradiol in a Man with Aromatase Deficiency","volume":"337","author":"Carani","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"bqab210","DOI":"10.1210\/endocr\/bqab210","article-title":"Fetal Estrogens Are Not Involved in Sex Determination But Critical for Early Ovarian Differentiation in Rabbits","volume":"163","author":"Jolivet","year":"2022","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1186\/gb-2007-8-2-r19","article-title":"QBase Relative Quantification Framework and Software for Management and Automated Analysis of Real-Time Quantitative PCR Data","volume":"8","author":"Hellemans","year":"2007","journal-title":"Genome Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jsbmb.2015.05.002","article-title":"Evidence of Estrone-Sulfate Uptake Modification in Young and Middle-Aged Rat Prostate","volume":"152","author":"Giton","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1530\/JOE-18-0313","article-title":"FSH Inhibits AMH to Support Ovarian Estradiol Synthesis in Infantile Mice","volume":"240","author":"Devillers","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Perrier, J.-P., Sellem, E., Pr\u00e9zelin, A., Gasselin, M., Jouneau, L., Piumi, F., Al Adhami, H., Weber, M., Fritz, S., and Boichard, D. (2018). A Multi-Scale Analysis of Bull Sperm Methylome Revealed Both Species Peculiarities and Conserved Tissue-Specific Features. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4764-0"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.yexcr.2006.03.006","article-title":"LUMA (LUminometric Methylation Assay)\u2014A High Throughput Method to the Analysis of Genomic DNA Methylation","volume":"312","author":"Karimi","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/humrep\/deh555","article-title":"Cytoplasmic Droplets: The Good, the Bad or Just Confusing?","volume":"20","author":"Cooper","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e676","DOI":"10.1038\/cddis.2013.203","article-title":"Exposure to Bisphenol A Disrupts Meiotic Progression during Spermatogenesis in Adult Rats through Estrogen-like Activity","volume":"4","author":"Liu","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/andr.12320","article-title":"Molecular Changes and Signaling Events Occurring in Sperm during Epididymal Maturation","volume":"5","author":"Gervasi","year":"2017","journal-title":"Andrology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1530\/REP-13-0058","article-title":"Epididymosomes, Prostasomes, and Liposomes: Their Roles in Mammalian Male Reproductive Physiology","volume":"146","author":"Sullivan","year":"2013","journal-title":"Reproduction"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2070\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:50Z","timestamp":1760145170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,8]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112070"],"URL":"https:\/\/doi.org\/10.3390\/genes13112070","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,8]]}}}