人类胎儿和成人卵巢中的类固醇激素概况。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Reproductive Biology and Endocrinology Pub Date : 2024-05-22 DOI:10.1186/s12958-024-01233-7
Paraskevi Vazakidou, Sara Evangelista, Tianyi Li, Laetitia L Lecante, Kristine Rosenberg, Jacco Koekkoek, Andres Salumets, Agne Velthut-Meikas, Pauliina Damdimopoulou, Séverine Mazaud-Guittot, Paul A Fowler, Pim E G Leonards, Majorie B M van Duursen
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引用次数: 0

摘要

背景:妇女的生殖系统在一生中不同的敏感期接触到的化学物质会扰乱内分泌系统,从而危及生殖系统。类固醇激素水平是包括卵巢在内的人类生殖系统正常发育和功能的基础。本研究旨在阐明人类卵巢不同生命阶段的类固醇生成情况:我们开发了一种灵敏而特异的 LC-MS/MS 方法,用于检测 21 种重要的类固醇激素,并在不同生命阶段对其进行了测定:从选择性终止正常妊娠的人类胎儿卵巢培养基中、从剖腹产患者的成年卵巢培养基中以及从接受不孕症治疗的妇女卵泡液中。通过参数检验计算出类固醇激素水平及其比率在统计学上的重大差异。应用主成分分析(PCA)探讨了卵巢衍生类固醇生成特征的聚类:结果:对 21 种类固醇激素进行比较后发现,不同卵巢来源的类固醇特征之间存在明显差异。有趣的是,我们发现在妊娠第一和第二个三个月的胎儿及成人卵巢组织培养物中,典型和 "后门 "途径的类固醇激素和皮质类固醇都有生物合成。17α-estradiol 是 17β-estradiol 的一种效力较弱的天然异构体,仅在卵泡液中被检测到。对卵巢来源特征进行 PCA 分析后发现,以下几种物质组成了一个群集:成人卵巢组织培养物的雄激素水平相对较高;胎儿卵巢组织培养物的雌激素水平相对较低;卵泡液的雄激素水平最低,但皮质类固醇、孕激素和雌二醇水平最高。此外,特定类固醇激素的比率显示,雌二醇/睾酮和雌酮/雄烯二酮较高(表明 CYP19A1 活性较高):人类卵巢可从头合成非规范和 "后门 "途径的类固醇激素和皮质类固醇。阐明人类卵巢中的类固醇概况有助于我们更好地了解卵巢的生理、生命阶段依赖性和类固醇生成能力,并为机理研究提供信息,以确定影响女性生殖的内分泌干扰化学物质。
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The profile of steroid hormones in human fetal and adult ovaries.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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来源期刊
Reproductive Biology and Endocrinology
Reproductive Biology and Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.30%
发文量
161
审稿时长
4-8 weeks
期刊介绍: Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences. The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
期刊最新文献
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