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Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We have developed a sensitive and specific LC-MS\/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and \u201cbackdoor\u201d pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17\u03b1-estradiol, a less potent naturally occurring isomer of 17\u03b2-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol\/ testosterone and estrone\/androstenedione (indicating higher CYP19A1 activity,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and higher 17-hydroxyprogesterone\/progesterone and dehydroepiandrosterone \/androstenedione (indicating higher CYP17A1 activity,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) in fetal compared to adult ovarian tissue cultures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Human ovaries demonstrate de novo synthesis of non-canonical and \u201cbackdoor\u201d pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12958-024-01233-7","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T03:01:47Z","timestamp":1716346907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The profile of steroid hormones in human fetal and adult ovaries"],"prefix":"10.1186","volume":"22","author":[{"given":"Paraskevi","family":"Vazakidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Evangelista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia L.","family":"Lecante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacco","family":"Koekkoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Salumets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agne","family":"Velthut-Meikas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauliina","family":"Damdimopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Mazaud-Guittot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim E.G.","family":"Leonards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majorie B.M.","family":"van Duursen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"1233_CR1","doi-asserted-by":"crossref","unstructured":"Johansson HKL, Svingen T, Fowler PA, Vinggaard AM, Boberg J. 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Women who underwent C-section gave consent to participate in the research project investigating the effects of EDCs on ovaries at Karolinska University Hospital Huddinge in Stockholm, Sweden, in accordance with the Declaration of Helsinki. Women who received IVF treatment and from whose follicular fluid samples were collected, were informed regarding the study, and they signed an informed written consent form complying with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"60"}}