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The profile of steroid hormones in human fetal and adult ovaries
Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This stud...
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Published in: | Reproductive biology and endocrinology 2024-05, Vol.22 (1), p.60-60, Article 60 |
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creator | Vazakidou, Paraskevi Evangelista, Sara Li, Tianyi Lecante, Laetitia L Rosenberg, Kristine Koekkoek, Jacco Salumets, Andres Velthut-Meikas, Agne Damdimopoulou, Pauliina Mazaud-Guittot, Séverine Fowler, Paul A Leonards, Pim E G van Duursen, Majorie B M |
description | Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. 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.
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.
Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-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, p |
doi_str_mv | 10.1186/s12958-024-01233-7 |
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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.
Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-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, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures.
Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" 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.</description><identifier>ISSN: 1477-7827</identifier><identifier>EISSN: 1477-7827</identifier><identifier>DOI: 10.1186/s12958-024-01233-7</identifier><identifier>PMID: 38778396</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>17 alpha estradiol ; Adult ; Analysis ; Backdoor pathway ; Cesarean section ; Chromatography, Liquid ; Corticosteroids ; Dehydroepiandrosterone ; Embryonic development ; Estradiol ; Estradiol - metabolism ; Female ; Fetal and adult ovarian steroidogenesis ; Fetus - metabolism ; Follicular Fluid - chemistry ; Follicular Fluid - metabolism ; Gonadal Steroid Hormones - analysis ; Gonadal Steroid Hormones - biosynthesis ; Gonadal Steroid Hormones - metabolism ; Humans ; Hydroxylases ; Hydroxyprogesterone ; Life Sciences ; Ovary - metabolism ; Pregnancy ; Tandem Mass Spectrometry ; Testosterone</subject><ispartof>Reproductive biology and endocrinology, 2024-05, Vol.22 (1), p.60-60, Article 60</ispartof><rights>2024. The Author(s).</rights><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><rights>Attribution</rights><rights>The Author(s) 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c559t-305892a1fc7250cb4e9b2c5daa8c1a6881b386a77a917f16d0071708ec33af853</cites><orcidid>0000-0002-3185-7803 ; 0000-0002-3838-9731 ; 0000-0001-8458-0855 ; 0000-0003-0566-4124 ; 0000-0002-6159-1540 ; 0000-0002-7112-3169 ; 0000-0003-1927-9016 ; 0000-0003-4247-5840 ; 0000-0002-5231-084X ; 0000-0002-1251-8160</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110185/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110185/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,36992,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38778396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04605056$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Vazakidou, Paraskevi</creatorcontrib><creatorcontrib>Evangelista, Sara</creatorcontrib><creatorcontrib>Li, Tianyi</creatorcontrib><creatorcontrib>Lecante, Laetitia L</creatorcontrib><creatorcontrib>Rosenberg, Kristine</creatorcontrib><creatorcontrib>Koekkoek, Jacco</creatorcontrib><creatorcontrib>Salumets, Andres</creatorcontrib><creatorcontrib>Velthut-Meikas, Agne</creatorcontrib><creatorcontrib>Damdimopoulou, Pauliina</creatorcontrib><creatorcontrib>Mazaud-Guittot, Séverine</creatorcontrib><creatorcontrib>Fowler, Paul A</creatorcontrib><creatorcontrib>Leonards, Pim E G</creatorcontrib><creatorcontrib>van Duursen, Majorie B M</creatorcontrib><title>The profile of steroid hormones in human fetal and adult ovaries</title><title>Reproductive biology and endocrinology</title><addtitle>Reprod Biol Endocrinol</addtitle><description>Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. 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.
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.
Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-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, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures.
Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" 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.</description><subject>17 alpha estradiol</subject><subject>Adult</subject><subject>Analysis</subject><subject>Backdoor pathway</subject><subject>Cesarean section</subject><subject>Chromatography, Liquid</subject><subject>Corticosteroids</subject><subject>Dehydroepiandrosterone</subject><subject>Embryonic development</subject><subject>Estradiol</subject><subject>Estradiol - metabolism</subject><subject>Female</subject><subject>Fetal and adult ovarian steroidogenesis</subject><subject>Fetus - metabolism</subject><subject>Follicular Fluid - chemistry</subject><subject>Follicular Fluid - metabolism</subject><subject>Gonadal Steroid Hormones - analysis</subject><subject>Gonadal Steroid Hormones - biosynthesis</subject><subject>Gonadal Steroid Hormones - metabolism</subject><subject>Humans</subject><subject>Hydroxylases</subject><subject>Hydroxyprogesterone</subject><subject>Life Sciences</subject><subject>Ovary - metabolism</subject><subject>Pregnancy</subject><subject>Tandem Mass Spectrometry</subject><subject>Testosterone</subject><issn>1477-7827</issn><issn>1477-7827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptUk1v1DAQjRCIfsAf4IAicYFDiu3EXydYVZRWWolLOVsTe7JxlcSLnV2Jf493U6ouwj7YGr_3ZjzziuIdJVeUKvE5Uaa5qghrKkJZXVfyRXFOGykrqZh8-ex-Vlyk9EAII0SJ18VZraRUtRbnxdf7HsttDJ0fsAxdmWaMwbuyD3EME6bST2W_G2EqO5xhKGFyJbjdMJdhD9FjelO86mBI-PbxvCx-3ny7v76t1j--312v1pXlXM9VTbjSDGhnJePEtg3qllnuAJSlIJSiba0ESAmayo4KR4ikkii0dQ2d4vVlcbfougAPZhv9CPG3CeDNMRDixkCcvR3QINekZSQrO97oFqEVRKBG1E4odCJrfVm0trt2RGdxmiMMJ6KnL5PvzSbsDc2L0GM1nxaF_h_e7WptDjHSCMIJF3uasR8fs8Xwa4dpNqNPFocBJgy7ZHJrNOOCNixDPyzQDeR_-KkLOb09wM1K6kYzKiXJqKv_oPJ2OHqbp3YY5imBLQQbQ0oRu6eSKTEHK5nFSiZbyRytZGQmvX_epCfKX-_UfwBdUMHw</recordid><startdate>20240522</startdate><enddate>20240522</enddate><creator>Vazakidou, Paraskevi</creator><creator>Evangelista, Sara</creator><creator>Li, Tianyi</creator><creator>Lecante, Laetitia L</creator><creator>Rosenberg, Kristine</creator><creator>Koekkoek, Jacco</creator><creator>Salumets, Andres</creator><creator>Velthut-Meikas, Agne</creator><creator>Damdimopoulou, Pauliina</creator><creator>Mazaud-Guittot, Séverine</creator><creator>Fowler, Paul A</creator><creator>Leonards, Pim E G</creator><creator>van Duursen, Majorie B M</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3185-7803</orcidid><orcidid>https://orcid.org/0000-0002-3838-9731</orcidid><orcidid>https://orcid.org/0000-0001-8458-0855</orcidid><orcidid>https://orcid.org/0000-0003-0566-4124</orcidid><orcidid>https://orcid.org/0000-0002-6159-1540</orcidid><orcidid>https://orcid.org/0000-0002-7112-3169</orcidid><orcidid>https://orcid.org/0000-0003-1927-9016</orcidid><orcidid>https://orcid.org/0000-0003-4247-5840</orcidid><orcidid>https://orcid.org/0000-0002-5231-084X</orcidid><orcidid>https://orcid.org/0000-0002-1251-8160</orcidid></search><sort><creationdate>20240522</creationdate><title>The profile of steroid hormones in human fetal and adult ovaries</title><author>Vazakidou, Paraskevi ; Evangelista, Sara ; Li, Tianyi ; Lecante, Laetitia L ; Rosenberg, Kristine ; Koekkoek, Jacco ; Salumets, Andres ; Velthut-Meikas, Agne ; Damdimopoulou, Pauliina ; Mazaud-Guittot, Séverine ; Fowler, Paul A ; Leonards, Pim E G ; van Duursen, Majorie B M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-305892a1fc7250cb4e9b2c5daa8c1a6881b386a77a917f16d0071708ec33af853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>17 alpha estradiol</topic><topic>Adult</topic><topic>Analysis</topic><topic>Backdoor pathway</topic><topic>Cesarean section</topic><topic>Chromatography, Liquid</topic><topic>Corticosteroids</topic><topic>Dehydroepiandrosterone</topic><topic>Embryonic development</topic><topic>Estradiol</topic><topic>Estradiol - metabolism</topic><topic>Female</topic><topic>Fetal and adult ovarian steroidogenesis</topic><topic>Fetus - metabolism</topic><topic>Follicular Fluid - chemistry</topic><topic>Follicular Fluid - metabolism</topic><topic>Gonadal Steroid Hormones - analysis</topic><topic>Gonadal Steroid Hormones - biosynthesis</topic><topic>Gonadal Steroid Hormones - metabolism</topic><topic>Humans</topic><topic>Hydroxylases</topic><topic>Hydroxyprogesterone</topic><topic>Life Sciences</topic><topic>Ovary - metabolism</topic><topic>Pregnancy</topic><topic>Tandem Mass Spectrometry</topic><topic>Testosterone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vazakidou, Paraskevi</creatorcontrib><creatorcontrib>Evangelista, Sara</creatorcontrib><creatorcontrib>Li, Tianyi</creatorcontrib><creatorcontrib>Lecante, Laetitia L</creatorcontrib><creatorcontrib>Rosenberg, Kristine</creatorcontrib><creatorcontrib>Koekkoek, Jacco</creatorcontrib><creatorcontrib>Salumets, Andres</creatorcontrib><creatorcontrib>Velthut-Meikas, Agne</creatorcontrib><creatorcontrib>Damdimopoulou, Pauliina</creatorcontrib><creatorcontrib>Mazaud-Guittot, Séverine</creatorcontrib><creatorcontrib>Fowler, Paul A</creatorcontrib><creatorcontrib>Leonards, Pim E G</creatorcontrib><creatorcontrib>van Duursen, Majorie B M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Reproductive biology and endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vazakidou, Paraskevi</au><au>Evangelista, Sara</au><au>Li, Tianyi</au><au>Lecante, Laetitia L</au><au>Rosenberg, Kristine</au><au>Koekkoek, Jacco</au><au>Salumets, Andres</au><au>Velthut-Meikas, Agne</au><au>Damdimopoulou, Pauliina</au><au>Mazaud-Guittot, Séverine</au><au>Fowler, Paul A</au><au>Leonards, Pim E G</au><au>van Duursen, Majorie B M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The profile of steroid hormones in human fetal and adult ovaries</atitle><jtitle>Reproductive biology and endocrinology</jtitle><addtitle>Reprod Biol Endocrinol</addtitle><date>2024-05-22</date><risdate>2024</risdate><volume>22</volume><issue>1</issue><spage>60</spage><epage>60</epage><pages>60-60</pages><artnum>60</artnum><issn>1477-7827</issn><eissn>1477-7827</eissn><abstract>Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. 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.
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.
Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-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, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures.
Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" 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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>38778396</pmid><doi>10.1186/s12958-024-01233-7</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3185-7803</orcidid><orcidid>https://orcid.org/0000-0002-3838-9731</orcidid><orcidid>https://orcid.org/0000-0001-8458-0855</orcidid><orcidid>https://orcid.org/0000-0003-0566-4124</orcidid><orcidid>https://orcid.org/0000-0002-6159-1540</orcidid><orcidid>https://orcid.org/0000-0002-7112-3169</orcidid><orcidid>https://orcid.org/0000-0003-1927-9016</orcidid><orcidid>https://orcid.org/0000-0003-4247-5840</orcidid><orcidid>https://orcid.org/0000-0002-5231-084X</orcidid><orcidid>https://orcid.org/0000-0002-1251-8160</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 17 alpha estradiol Adult Analysis Backdoor pathway Cesarean section Chromatography, Liquid Corticosteroids Dehydroepiandrosterone Embryonic development Estradiol Estradiol - metabolism Female Fetal and adult ovarian steroidogenesis Fetus - metabolism Follicular Fluid - chemistry Follicular Fluid - metabolism Gonadal Steroid Hormones - analysis Gonadal Steroid Hormones - biosynthesis Gonadal Steroid Hormones - metabolism Humans Hydroxylases Hydroxyprogesterone Life Sciences Ovary - metabolism Pregnancy Tandem Mass Spectrometry Testosterone |
title | The profile of steroid hormones in human fetal and adult ovaries |
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