Evidence map›Paper›PMID 38778396›Full record

ArticleReproductive biology and endocrinology : RB&E2024

The profile of steroid hormones in human fetal and adult ovaries.

Paraskevi Vazakidou, Sara Evangelista, Tianyi Li, Laetitia L Lecante, Kristine Rosenberg, Jacco Koekkoek, Andres Salumets, Agne Velthut-Meikas, Pauliina Damdimopoulou, Séverine Mazaud-Guittot and 3 more

Registry-linked trialAbstract read
In one paragraph

Article in Reproductive biology and endocrinology : RB&E, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04613583 (Normal Development of the Human Fetus and the Influences and Mechanisms by Which That Development Occurs and is Perturbed), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04613583 recruitingnot on this map

Normal Development of the Human Fetus and the Influences and Mechanisms by Which That Development Occurs and is Perturbed

TypeobservationalSponsorUniversity of AberdeenRan2016 to 2028Enrolled1,200ConditionsFetal Developmental Abnormality, Fetal Development, Human, Life StyleArmsSAFeR fetuses
3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Study of Estrogen Receptor Alpha Gene Polymorphisms (International journal of molecular sciences · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. microPublication biology · 2025
    Article
  11. Review
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Paraskevi VazakidouSection Environment and Health, Amsterdam Institute for Life and Environment, De Boelelaan 1085, Amsterdam, 1081 HV, The Netherlands. p.vazakidou@vu.nl.
Sara EvangelistaSection Environment and Health, Amsterdam Institute for Life and Environment, De Boelelaan 1085, Amsterdam, 1081 HV, The Netherlands.
Tianyi LiDepartment of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, SE-14186, Sweden.
Laetitia L LecanteInstitute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Kristine RosenbergDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
Jacco KoekkoekSection Environment and Health, Amsterdam Institute for Life and Environment, De Boelelaan 1085, Amsterdam, 1081 HV, The Netherlands.
Andres SalumetsDepartment of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, SE-14186, Sweden.
Agne Velthut-MeikasDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
Pauliina DamdimopoulouDepartment of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, SE-14186, Sweden.
Séverine Mazaud-GuittotUniv Rennes, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Inserm, Rennes, F-35000, France.
Paul A FowlerInstitute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Pim E G LeonardsSection Environment and Health, Amsterdam Institute for Life and Environment, De Boelelaan 1085, Amsterdam, 1081 HV, The Netherlands.
Majorie B M van DuursenSection Environment and Health, Amsterdam Institute for Life and Environment, De Boelelaan 1085, Amsterdam, 1081 HV, The Netherlands.

Funding

Estonian Research Council PRG1076Estonian Research Council PSG608European research project FREIA 825100Horizon 2020 innovation grant (ERIN) EU952516Swedish Research Council FORMAS 2020-01621 and 2018-02280
6 · The paper itself

Abstract

backgroundReproduction 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.

methodsWe 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.

resultsComparison 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.

conclusionsHuman 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.

Indexed as

FetusOvaryAdultChromatography, LiquidEstradiolFemaleFollicular FluidGonadal Steroid HormonesHumansPregnancyTandem Mass SpectrometryEstradiolGonadal Steroid Hormones17 alpha estradiolBackdoor pathwayCorticosteroidsFetal and adult ovarian steroidogenesis

Identifiers

PMID38778396
PMCPMC11110185

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.