Mediating role of maternal cortisol in the association between maternal serum creatinine and fetal cortisol exposure

IF 3.4 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Psychoneuroendocrinology Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI:10.1016/j.psyneuen.2026.107772

Ziyan Lin , Zhiqi Zhang , Guoping Yang , Nan Wang , Jinfu Peng

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引用次数: 0

Abstract

Background

Cortisol is the principal glucocorticoid regulated by the hypothalamic–pituitary–adrenal (HPA) axis and plays a crucial role in maintaining pregnancy and promoting fetal growth and development. Renal function is a key determinant of cortisol exposure. Given that serum creatinine serves as a key biomarker of renal function, it is plausible that maternal creatinine levels contribute to the regulation of fetal cortisol exposure, although the underlying mechanisms remain to be fully elucidated.

Objective

This study was designed to (1) examine the association between maternal serum creatinine and umbilical cord blood cortisol levels, (2) assess the potential mediating role of maternal cortisol in this relationship, and (3) investigate corresponding changes in the protein expression of placental 11β-HSD1 and 11β-HSD2.

Methods

This study employed a paired maternal–fetal design. At delivery, maternal serum, umbilical cord blood, and placental tissue were collected simultaneously from 103 mother–newborn pairs. Cortisol and cortisone levels in maternal and cord blood were measured, and protein expression of 11β-HSD1 and 11β-HSD2 in placental tissue was analyzed. Correlation and mediation analyses were performed to assess the relationships among maternal serum creatinine, maternal cortisol, and cord blood cortisol.

Results

Each unit increase in maternal serum creatinine was associated with a significant decrease in cord blood cortisol levels. Maternal cortisol levels were positively correlated with cord blood cortisol. Mediation analysis showed that maternal cortisol mediated 31.75 % of the association between maternal creatinine and cord blood cortisol. In the high-creatinine conditions, placental expression of 11β-HSD1 was significantly decreased, while expression of 11β-HSD2 was increased.

Conclusion

Maternal cortisol showed evidence of partial mediation in the association between maternal renal function and fetal cortisol exposure. This observational finding highlights a potential link between maternal renal function and fetal glucocorticoid exposure and provides a basis for future studies to investigate the role of placental glucocorticoid regulation and fetal HPA axis development.

查看原文本刊更多论文

母体皮质醇在母体血清肌酐与胎儿皮质醇暴露关系中的中介作用。

背景：皮质醇是受下丘脑-垂体-肾上腺（HPA）轴调节的主要糖皮质激素，在维持妊娠和促进胎儿生长发育中起着至关重要的作用。肾功能是皮质醇暴露的关键决定因素。鉴于血清肌酐是肾功能的关键生物标志物，母体肌酐水平有助于胎儿皮质醇暴露的调节是合理的，尽管潜在的机制仍有待充分阐明。目的：本研究旨在(1)研究母体血清肌酐与脐带血皮质醇水平的相关性，(2)评估母体皮质醇在这一关系中的潜在介导作用，(3)研究胎盘11β-HSD1和11β-HSD2蛋白表达的相应变化。方法：本研究采用母胎配对设计。分娩时，同时采集103对母婴血清、脐带血和胎盘组织。测定母血和脐带血中皮质醇和可的松水平，分析胎盘组织中11β-HSD1和11β-HSD2蛋白表达。通过相关分析和中介分析评估产妇血清肌酐、产妇皮质醇和脐带血皮质醇之间的关系。结果：母亲血清肌酐每增加一个单位与脐带血皮质醇水平显著降低相关。母体皮质醇水平与脐带血皮质醇水平呈正相关。中介分析显示，母体皮质醇介导了母体肌酐与脐带血皮质醇相关性的31.75% %。在高肌酐条件下，胎盘11β-HSD1表达显著降低，而11β-HSD2表达升高。结论：母体皮质醇在母体肾功能与胎儿皮质醇暴露的关系中起部分中介作用。这一观察性发现强调了母体肾功能与胎儿糖皮质激素暴露之间的潜在联系，并为进一步研究胎盘糖皮质激素调节与胎儿HPA轴发育的作用提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychoneuroendocrinology 医学-精神病学

CiteScore

7.40

自引率

8.10%

发文量

268

审稿时长

66 days

期刊介绍： Psychoneuroendocrinology publishes papers dealing with the interrelated disciplines of psychology, neurobiology, endocrinology, immunology, neurology, and psychiatry, with an emphasis on multidisciplinary studies aiming at integrating these disciplines in terms of either basic research or clinical implications. One of the main goals is to understand how a variety of psychobiological factors interact in the expression of the stress response as it relates to the development and/or maintenance of neuropsychiatric illnesses.