{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:53:03Z","timestamp":1787028783497,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The adrenal medulla and organs of Zuckerkandl consist of chromaffin cells that produce, store, and secrete catecholamines. In humans, the adrenal medulla is known to function throughout postnatal life, while the organs of Zuckerkandl degenerate by 2\u20133 years of postnatal life. Although the history of investigation of chromaffin cells goes back more than a century, little is known about the reciprocal organogenesis of the adrenal glands and organs of Zuckerkandl during human fetal development. In the current study, we compared these two organs using serial sectioning, routine histological staining, and immunohistochemical reactions in human embryos, prefetuses, and fetuses from 8 to 26 gestational weeks. In our study, we used antibodies for tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase, which are enzymes of catecholamine synthesis, \u03b2-III tubulin, and S100. We found two morphological cell types (large and small) in the developing ganglia, organs of Zuckerkandl, and adrenal medulla, and two migration patterns of large cells and small cells. The immunohistochemical characteristics of these cells were determined. We revealed that the number of small cells increased significantly at the ages from 16 to 21\u201322 gestational weeks, followed by a decrease at 22.5\u201326 gestational weeks. The presence of two large cell subpopulations was suggested\u2014those that migrate primarily from organs of the Zuckerkandl region and those that differentiate later from the small cells. We also determined that 12 gestational weeks was the age of the first appearance of phenylethanolamine N-methyltransferase reactivity in developing chromaffin cells, temporally correlating with synaptogenesis events. This is important data in the light of the controversial glucocorticoid theory of phenylethanolamine N-methyltransferase induction in humans.<\/jats:p>","DOI":"10.3390\/life15081214","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T06:37:47Z","timestamp":1754030267000},"page":"1214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Developmental Parallels Between the Human Organs of Zuckerkandl and Adrenal Medulla"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-7760","authenticated-orcid":false,"given":"Ekaterina","family":"Otlyga","sequence":"first","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-3383","authenticated-orcid":false,"given":"Dmitry","family":"Otlyga","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-5393","authenticated-orcid":false,"given":"Olga","family":"Junemann","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9692-3616","authenticated-orcid":false,"given":"Yuliya","family":"Krivova","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0515-8275","authenticated-orcid":false,"given":"Alexandra","family":"Proshchina","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-4132","authenticated-orcid":false,"given":"Anastasia","family":"Kharlamova","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-8161","authenticated-orcid":false,"given":"Victoria I.","family":"Gulimova","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6844-700X","authenticated-orcid":false,"given":"Gleb","family":"Sonin","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Saveliev","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","first-page":"455","article-title":"Post-natal fate of the abdominal para-aortic bodies in man","volume":"88","author":"Coupland","year":"1954","journal-title":"J. Anat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1365-2826.2012.02367.x","article-title":"Cell Loss and Autophagy in the Extra-Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling","volume":"25","author":"Schober","year":"2012","journal-title":"J. Neuroendocrinol."},{"key":"ref_3","unstructured":"Smitten, N.A. (1972). Sympatho-Adrenal System in Phylogenesis and Ontogenesis, Nauka."},{"key":"ref_4","first-page":"1","article-title":"Development of catecholamine-storing cells in human fetal paraganglia and adrenal medulla. A histochemical and electron microscopical study","volume":"368","author":"Hervonen","year":"1971","journal-title":"Acta Physiol. Scand."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-4886(90)90001-9","article-title":"Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins","volume":"108","author":"Molenaar","year":"1990","journal-title":"Exp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s41588-021-00818-x","article-title":"Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin","volume":"53","author":"Kameneva","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1242\/jeb.183.1.165","article-title":"Storage and release of catecholamines from the chromaffin tissue of the Atlantic hagfish Myxine glutinosa","volume":"183","author":"Perry","year":"1993","journal-title":"J. Exp. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1515\/jpme.1978.6.1.39","article-title":"The secretion of catecholamines in newborn babies with special reference to fetal distress","volume":"6","author":"Nakai","year":"1978","journal-title":"J. Perinat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1016\/S0021-9258(18)96620-2","article-title":"Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenal cortical steroids","volume":"241","author":"Wurtman","year":"1966","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF00712926","article-title":"Glucocorticoids stimulate transcription of the rat phenylethanolamine N-methyltransferase (PNMT) gene in vivo and in vitro","volume":"12","author":"Evinger","year":"1992","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0306-9877(95)90508-1","article-title":"Local transfer of hormones between blood vessels within the adrenal gland may explain the functional interaction between the adrenal cortex and medulla","volume":"44","author":"Carter","year":"1995","journal-title":"Med. Hypotheses"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1242\/dev.126.13.2935","article-title":"Analysis of mice carrying targeted mutations of the glucocorticoid receptor gene argues against an essential role of glucocorticoid signalling for generating adrenal chromaffin cells","volume":"126","author":"Finotto","year":"1999","journal-title":"Development"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1677\/joe.0.0340479","article-title":"The human adrenal gland with special reference to the vasculature","volume":"34","author":"Dobbie","year":"1966","journal-title":"J. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/aja.1001640103","article-title":"Microcirculation of the rat adrenal gland: A scanning electron microscope study of vascular casts","volume":"164","author":"Kikuta","year":"1982","journal-title":"Am. J. Anat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0010-4035(72)90059-6","article-title":"Epinephrine biosynthesis in Petromyzon marinus (cyclostoma) and Salimo gairdneri (teleost)","volume":"3","author":"Mazeaud","year":"1972","journal-title":"Comp. Gen. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41588-021-00806-1","article-title":"Single-Cell Transcriptomic Analyses Provide Insights into the Developmental Origins of Neuroblastoma","volume":"53","author":"Jansky","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_18","unstructured":"Milovanov, A.P., and Saveliev, S.V. (2006). Rational periodization of prenatal human development and methodical aspects of embryology. Prenatal Human Development, MDV."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s10517-020-04807-8","article-title":"Immunohistochemical Study of Dark and Progenitor Carotid Body Cells: Artefacts or Real Subtypes?","volume":"168","author":"Otlyga","year":"2020","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_20","first-page":"605","article-title":"Histogenesis of the human adrenal medulla. An evaluation of the ontogeny of chromaffin and nonchromaffin lineages","volume":"137","author":"Cooper","year":"1990","journal-title":"Am. J. Pathol."},{"key":"ref_21","unstructured":"Golub, D.M. (1936). Development of Adrenal Glands and Its\u2019 Innervation in Human and Some Animals, Publishing House of the Academy of Sciences of the Byelorussian SSR."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/BF00217246","article-title":"Sustentacular cells in the fetal human adrenal medulla are immunoreactive with antibodies to brain S-100 protein","volume":"236","author":"Iwanaga","year":"1984","journal-title":"Cell Tissue Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/(SICI)1097-0185(199803)250:3<335::AID-AR8>3.0.CO;2-Z","article-title":"Class III \u03b2-Tubulin isotype (\u03b2 III) in the adrenal medulla: I. Localization in the developing human adrenal medulla","volume":"250","author":"Katsetos","year":"1998","journal-title":"Anat. Rec."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jorgensen, J.M., Lomholt, J.P., Weber, R.E., and Malte, H. (1998). The Control of Catecholamine Secretion in Hagfishes. The Biology of Hagfishes, Springer Science + Business.","DOI":"10.1007\/978-94-011-5834-3"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jorgensen, J.M., Lomholt, J.P., Weber, R.E., and Malte, H. (1998). The autonomic nervous system and chromaffin tissue in hagfishes. The Biology of Hagfishes, Springer Science + Business.","DOI":"10.1007\/978-94-011-5834-3"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Otlyga, D., Tsvetkova, E., Junemann, O., and Saveliev, S. (2021). Immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158222"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.neulet.2020.135163","article-title":"Regulation of Gene expression at the neuromuscular Junction","volume":"735","author":"Belotti","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7321","DOI":"10.1007\/s12035-019-1593-3","article-title":"Neurogranin Expression Is Regulated by Synaptic Activity and Promotes Synaptogenesis in Cultured Hippocampal Neurons","volume":"56","author":"Soriano","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5734","DOI":"10.1073\/pnas.92.12.5734","article-title":"Somatodendritic expression of an immediate early gene is regulated by synaptic activity","volume":"92","author":"Link","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF00278463","article-title":"Development of the adrenal medullary cells in rats with reference to synaptogenesis","volume":"179","author":"Daikoku","year":"1977","journal-title":"Cell Tissue Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1985.sp015536","article-title":"Adrenomedullary function in the neonatal rat: Responses to acute hypoxia","volume":"358","author":"Seidler","year":"1985","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1210\/er.2010-0001","article-title":"Development and function of the human fetal adrenal cortex: A key component in the feto-placental unit","volume":"32","author":"Ishimoto","year":"2011","journal-title":"Endocr. Rev."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/8\/1214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:20:09Z","timestamp":1760034009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/8\/1214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["life15081214"],"URL":"https:\/\/doi.org\/10.3390\/life15081214","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]}}}