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Background <p>Complicated pregnancies, including preeclampsia (PE), gestational diabetes mellitus (GDM), and fetal growth restriction (FGR), are associated with oxidative stress, sterile inflammation, and disrupted fluid homeostasis at the maternal-fetal interface. This study investigated the expression of aquaporin-1 (AQP-1), aquaporin-9 (AQP-9), aquaporin-11 (AQP-11), calponin 2 (CNN2), advanced glycation end products (AGE), receptor for advanced glycation end products (RAGE), high mobility group box 1 (HMGB1), and calprotectin in placental, amniotic, and chorionic tissues of women with complicated and uncomplicated term pregnancies.</p> Methods <p>This prospective comparative study enrolled 46 women undergoing elective cesarean delivery at term (37–41 weeks) at Haseki Training and Research Hospital, Istanbul (April–October 2022). Participants were divided into complicated (n = 23; GDM, PE, and/or FGR) and uncomplicated (n = 23) pregnancy groups. Tissue samples from placenta, amnion, and chorion were analyzed using commercial ELISA kits; results are expressed as ng/mL of tissue homogenate without normalization to total protein content. Benjamini-Hochberg false discovery rate (FDR) correction was applied across 24 primary comparisons. Effect sizes (Cohen's d) with 95% confidence intervals were calculated.</p> Results <p>After FDR correction, HMGB1 was significantly decreased in placental (37.57 ± 4.32 vs. 49.09 ± 8.48 ng/mL; p &lt; 0.001; d = 1.71) and amniotic tissues (39.38 ± 6.71 vs. 46.01 ± 8.53 ng/mL; p = 0.043; d = 0.86) of complicated pregnancies. Calprotectin was significantly reduced in amniotic tissue (8.09 ± 1.42 vs. 11.27 ± 2.09 ng/mL; p &lt; 0.001; d = 1.78). AQP-1, AQP-9, AQP-11, CNN2, AGE, and RAGE showed no significant between-group differences in any tissue after FDR correction.</p> Conclusions <p>HMGB1 and calprotectin, both RAGE ligands, demonstrated significant and large-effect reductions in gestational tissues of complicated term pregnancies, suggesting altered sterile inflammation at the maternal-fetal interface. These exploratory findings warrant replication in larger, disease-stratified cohorts to elucidate their biological and potential clinical significance.</p>

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Decreased HMGB1 and calprotectin expression in placental and fetal membrane tissues of complicated term pregnancies: a prospective comparative biomarker study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月5日

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  • Senem Karacabey Cakmak,
  • Meryem Kececi,
  • Numan Cim,
  • Ezgi Gungor,
  • Kubra Sevim Pehlivan,
  • Nurcihan Caliskan,
  • Ali Cetin

摘要

Background

Complicated pregnancies, including preeclampsia (PE), gestational diabetes mellitus (GDM), and fetal growth restriction (FGR), are associated with oxidative stress, sterile inflammation, and disrupted fluid homeostasis at the maternal-fetal interface. This study investigated the expression of aquaporin-1 (AQP-1), aquaporin-9 (AQP-9), aquaporin-11 (AQP-11), calponin 2 (CNN2), advanced glycation end products (AGE), receptor for advanced glycation end products (RAGE), high mobility group box 1 (HMGB1), and calprotectin in placental, amniotic, and chorionic tissues of women with complicated and uncomplicated term pregnancies.

Methods

This prospective comparative study enrolled 46 women undergoing elective cesarean delivery at term (37–41 weeks) at Haseki Training and Research Hospital, Istanbul (April–October 2022). Participants were divided into complicated (n = 23; GDM, PE, and/or FGR) and uncomplicated (n = 23) pregnancy groups. Tissue samples from placenta, amnion, and chorion were analyzed using commercial ELISA kits; results are expressed as ng/mL of tissue homogenate without normalization to total protein content. Benjamini-Hochberg false discovery rate (FDR) correction was applied across 24 primary comparisons. Effect sizes (Cohen's d) with 95% confidence intervals were calculated.

Results

After FDR correction, HMGB1 was significantly decreased in placental (37.57 ± 4.32 vs. 49.09 ± 8.48 ng/mL; p < 0.001; d = 1.71) and amniotic tissues (39.38 ± 6.71 vs. 46.01 ± 8.53 ng/mL; p = 0.043; d = 0.86) of complicated pregnancies. Calprotectin was significantly reduced in amniotic tissue (8.09 ± 1.42 vs. 11.27 ± 2.09 ng/mL; p < 0.001; d = 1.78). AQP-1, AQP-9, AQP-11, CNN2, AGE, and RAGE showed no significant between-group differences in any tissue after FDR correction.

Conclusions

HMGB1 and calprotectin, both RAGE ligands, demonstrated significant and large-effect reductions in gestational tissues of complicated term pregnancies, suggesting altered sterile inflammation at the maternal-fetal interface. These exploratory findings warrant replication in larger, disease-stratified cohorts to elucidate their biological and potential clinical significance.