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Differential Distribution of Tryptophan-Metabolites in Fetal and Maternal Circulations During Normotensive and Preeclamptic Pregnancies

  • Maternal Fetal Medicine/Biology: Original Article
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Abstract

Preeclampsia (PE) is a hypertensive pregnancy, which is a leading cause of maternal and fetal morbidity and mortality during pregnancy. L-Tryptophan (Trp) is an essential amino acid, which can be metabolized into various biologically active metabolites. However, the levels of many circulating Trp-metabolites in human normotensive pregnancies (NT) and PE are undetermined. This study quantified the levels of Trp-metabolites in maternal and umbilical vein sera from women with NT and PE. Paired maternal and umbilical blood samples were collected from singleton pregnant patients. Twenty-five Trp-metabolites were measured in serum samples using liquid chromatography with tandem mass spectrometry. The effects of L-kynurenine (Kyn) and indole-3-lactic acid (ILA), on function of human umbilical vein endothelial cells (HUVECs), were also determined. Twenty Trp-metabolites were detected. The levels of 9 Trp-metabolites including Kyn and ILA were higher (P < 0.05) in umbilical vein than maternal serum, whereas 2 (5-hydroxy-L-tryptophan and serotonin) were lower (P < 0.05) in umbilical vein compared to maternal serum. PE significantly (P < 0.05) elevated ILA levels in maternal and umbilical vein sera. Kyn dose-dependently decreased (P < 0.05) cell viability. Kyn and ILA dose- and time-dependently (P < 0.05) increased monolayer integrity in HUVECs. These data suggest that these Trp-metabolites are important in regulating endothelial function during pregnancy, and the elevated ILA in PE may antagonize increased endothelial permeability occurring in PE.

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Data Availability

Additional supporting data are available in the online-only Data Supplement.

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Acknowledgements

We would like to thank Laura Hogan, Ph.D., a Science Writer/Editor with the UW ICTR, for critically reading and editing this manuscript. We also thank Ms. Susanna Zheng, UW-Madison, for preparing the figure for this publication.

Funding

This study is supported by the NIH grants RO3 HD100778 (CZ), as well as American Heart Association awards 17POST33670283 and 19CDA34660348 (CZ). The project was also supported by Translational Basic and Clinical Pilot Award (JZ and CZ) from the UW Institute for Clinical and Translational Research (ICTR) and the Clinical and Translational Science Award program, through the NIH National Center for Advancing Translational Sciences, grant UL1TR002373.

Author information

Author notes

  1. Chi Zhou

    Present address: School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USA

  2. Ying-jie Zhao and Chi Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Wisconsin-Madison, PAB1 UnityPoint Health-Meriter Hospital, 202 S. Park Street, Madison, WI, 53715, USA

    Ying-jie Zhao, Chi Zhou, Hui-hui Li, Derek S. Boeldt & Jing Zheng

  2. Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Ying-jie Zhao

  3. Shanghai Key Laboratory of Maternal and Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China

    Ying-ying Wei & Kai Wang

  4. Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Hui-hui Li

  5. Cardiovascular Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China

    Wei Lei

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  1. Ying-jie Zhao
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  2. Chi Zhou
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Contributions

LW, KW, and JZ conceived the study. YYW and WK prepared blood serum samples. YJZ, CZ, HHL, DSB, and JZ prepared HUVECs, analyzed the data, and performed statistics. YJZ, CZ, HHL, WL, DSB, KW, and JZ wrote the manuscript. All authors revised the manuscript and approved the final manuscript.

Corresponding authors

Correspondence to Kai Wang or Jing Zheng.

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Ethics Approval

All procedures were conducted in accordance with the Declaration of Helsinki. All the tissue samples were collected with written informed consent. The blood sample collection was approved by the Scientific and Ethical Committee of Shanghai First Maternity and Infant Hospital, Tongji University (Protocol number: KS2013, approved on April 20, 2020). For HUVECs, the umbilical cord collection was approved by the Institutional Review Board of Meriter Hospital, and the Health Sciences Institutional Review Boards of the University of Wisconsin-Madison (Protocol number 2004–006, approved on July 26, 2018).

Consent to Participate

All patients consented to participate and for publication with de-identified patients’ information.

Conflict of Interest

The authors declare no competing interests.

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Zhao, Yj., Zhou, C., Wei, Yy. et al. Differential Distribution of Tryptophan-Metabolites in Fetal and Maternal Circulations During Normotensive and Preeclamptic Pregnancies. Reprod. Sci. 29, 1278–1286 (2022). https://doi.org/10.1007/s43032-021-00759-0

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