The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 8: 1415 - 1420

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.08.015

Treatise: Clinical Practice

Association between genetic variants in the promoter of PDE4D gene and the risk of intrauterine adhesions in patients after curettage abortion

  • Danting SHEN ,
  • Cong LI ,
  • Manlin SHI ,
  • Shuhua LIU ,
  • Anping LIN ,
  • Bin LIU
Expand
  • 1.Department of Gynecology，Shenzhen Baoan Women's and Children's Hospital，Shenzhen 510181，Guangdong，Chin
    2Maternal & Child Health Research Institute，Shenzhen Baoan Women's and Children's Hospital，Shenzhen 510181，Guangdong，China

Received date: 2025-12-25

  Online published: 2026-04-28

Fold

Abstract

Objective To investigate the association between genetic variants in the promoter region of the PDE4D gene and the risk of intrauterine adhesions in patients following curettage abortion. Methods This study conducted genotyping of two polymorphisms， rs7701573 and rs997421， in 113 patients diagnosed with intrauterine adhesions and 270 control subjects from the hospital who underwent curettage abortions between 2022 and 2023. Subsequently， we employed multiple logistic regression models to analyze their association with the risks of intrauterine adhesions. Results Individuals with rs997421 CT+TT genotypes had a lower risk of intrauterine adhesions （adjusted OR = 0.635， 95%CI： 0.408 - 0.988） compared to those with the rs997421 CC genotype. The protective effect was more pronounced in patients with more extensive cavity involvement of adhesions （adjusted OR = 0.518， 95%CI： 0.268 - 0.999） and in those with fibrous （Firm & Dense） adhesions （adjusted OR = 0.596， 95%CI： 0.371 - 0.956）. However， the rs7701573 polymorphism did not significantly affect the risk of intrauterine adhesions. To our knowledge， this study is the first to report the association between PDE4D gene polymorphisms and the risk of intrauterine adhesions after curettage abortion. Conclusions This study first indicates that the rs997421 polymorphism with the CT+TT genotype is associated with a reduced， protective risk of intrauterine adhesions， especially in patients with fibrous adhesions and extensive uterine cavity involvement. This provides new perspectives for preventing intrauterine adhesions after curettage abortion.

Key words： curettage abortion; intrauterine adhesion; PDE4D; polymorphisms

Cite this article

Danting SHEN , Cong LI , Manlin SHI , Shuhua LIU , Anping LIN , Bin LIU . Association between genetic variants in the promoter of PDE4D gene and the risk of intrauterine adhesions in patients after curettage abortion[J]. The Journal of Practical Medicine, 2026 , 42(8) : 1415 -1420 . DOI: 10.3969/j.issn.1006-5725.2026.08.015

References

[1] LEE W L， LIU C H， CHENG M， et al. Focus on the primary prevention of intrauterine adhesions： Current concept and vision［J］. Int J Mol Sci， 2021， 22（10）： 5175. doi：10.3390/ijms22105175 .
[2] EMINGR M， HALAJ M， MAL?áK M， et al. Prevention of intrauterine adhesions［J］. Ceska Gynekol， 2023， 88（3）： 210-213. doi：10.48095/cccg2023210 .
[3] 赵贝， 乔攀峰， 马爱华， 等. 连续3周期宫腔镜下冷刀分离术联合芬吗通及阿司匹林肠溶片对中重度宫腔粘连不孕患者胚胎移植的影响［J］. 生殖医学杂志， 2025， 34（7）： 899-904. doi：10.3969/j.issn.1004-3845.2025.07.005 .
[4] KHAN Z. Etiology， risk factors， and management of asherman syndrome［J］. Obstet Gynecol， 2023， 142（3）： 543-554. doi：10.1097/aog.0000000000005309 .
[5] GHATTI S， TOWERS G， PIKE M， et al. Incidence of intrauterine adhesions after myomectomy and association with intraoperative entry of the endometrial cavity［J］. J Minim Invasive Gynecol， 2025： S1553-S4650（25）01004-0. doi：10.1016/j.jmig.2025.12.023 .
[6] BARNES P J. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease［J］. J Allergy Clin Immunol， 2016， 138（1）： 16-27. doi：10.1016/j.jaci.2016.05.011 .
[7] 黄晓武.宫腔粘连的治疗及生育衔接［J］.中华生殖与避孕杂志，2025，45（9）：886-891. doi：10.3760/cma.j.cn101441-20250410-00179 .
[8] 祖珍玉， 罗敏， 申东翔， 等. 脂肪间充质干细胞及普兰尼克F127水凝胶复合物对宫腔粘连子宫内膜的修复作用［J］. 实用医学杂志， 2021， 37（19）： 2437-2441. doi：10.3969/j.issn.1006-5725.2021.19.001 .
[9] DREISLER E， KJER J J. Asherman's syndrome： Current perspectives on diagnosis and management［J］. Int J Womens Health， 2019， 11： 191-198. doi：10.2147/IJWH.S165474 .
[10] MéHATS C， JIN S C， WAHLSTROM J， et al. PDE4D plays a critical role in the control of airway smooth muscle contraction［J］. FASEB J， 2003， 17（13）： 1831-1841. doi：10.1096/fj.03-0274com .
[11] B?TTCHER R， DULLA K， VAN STRIJP D， et al. Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases［J］. Oncotarget， 2016， 7（43）： 70669-70684. doi：10.18632/oncotarget.12204 .
[12] TORPHY T J. Phosphodiesterase isozymes： Molecular targets for novel antiasthma agents［J］. Am J Respir Crit Care Med， 1998， 157（2）： 351-370. doi：10.1164/ajrccm.157.2.9708012 .
[13] 付晶. PDE4D抑制线粒体自噬促进心肌肥大和心力衰竭的作用研究［D］. 武汉： 华中科技大学， 2023.
[14] LANDELLS L J， SZILAGY C M， JONES N A， et al. Identification and quantification of phosphodiesterase 4 subtypes in CD4 and CD8 lymphocytes from healthy and asthmatic subjects［J］. Br J Pharmacol， 2001， 133（5）： 722-729. doi：10.1038/sj.bjp.0704120 .
[15] KERYER G， ALSAT E， TASKéN K， et al. Cyclic AMP-dependent protein kinases and human trophoblast cell differentiation in vitro ［J］. J Cell Sci， 1998， 111（7）： 995-1004. doi：10.1242/jcs.111.7.995 .
[16] YAMAGUCHI D T， HAHN T J， BEEKER T G， et al. Relationship of cAMP and calcium messenger systems in prostaglandin-stimulated UMR-106 cells［J］. J Biol Chem， 1988， 263（22）： 10745-10753. doi：10.1016/S0021-9258（18）38034-7 .
[17] KOHYAMA T， LIU X， KIM H J， et al. Prostacyclin analogs inhibit fibroblast migration［J］. Am J Physiol Lung Cell Mol Physiol， 2002， 283（2）： L428-L432. doi：10.1152/ajplung.00432.2001 .
[18] ZUO H， HAN B， POPPINGA W J， et al. Cigarette smoke up-regulates PDE3 and PDE4 to decrease cAMP in airway cells［J］. Br J Pharmacol， 2018， 175（14）： 2988-3006. doi：10.1111/bph.14347 .
[19] HSIEN LAI S， ZERVOUDAKIS G， CHOU J， et al. PDE4 subtypes in cancer［J］. Oncogene， 2020， 39（19）： 3791-3802. doi：10.1038/s41388-020-1258-8 .
[20] NUNEZ F J， SCHULTE N A， FOGEL D M， et al. Agonist-specific desensitization of PGE2-stimulated cAMP signaling due to upregulated phosphodiesterase expression in human lung fibroblasts［J］. Naunyn Schmiedebergs Arch Pharmacol， 2020， 393（5）： 843-856. doi：10.1007/s00210-019-01800-5 .
[21] CHO J H， HAN J S. Phospholipase D and its essential role in cancer［J］. Mol Cells， 2017， 40（11）： 805-813. doi：10.14348/molcells.2017.0241 .
[22] FINE J S， BYRNES H D， ZAVODNY P J， et al. Evaluation of signal transduction pathways in chemoattractant-induced human monocyte chemotaxis［J］. Inflammation， 2001， 25（2）： 61-67. doi：10.1023/a：1007152903135 .
[23] 王月， 杨弋. 磷酸二酯酶4抑制剂： 慢性鼻窦炎伴鼻息肉治疗的潜在新策略［J/OL］. 中国医学前沿杂志（电子版）， 2025， 17（11）： 81-88. doi：10.12037/YXQY.2025.11-11 .
[24] SHEN D， LI C， LIU S， et al. Association of LIN28B gene polymorphisms with intrauterine adhesions in patients after curettage abortion［J］. Biomedicines， 2024， 12（9）： 2044. doi：10.3390/biomedicines12092044 .
[25] NASR A L， AL-INANY H G， THABET S M， et al. A clinicohysteroscopic scoring system of intrauterine adhesions［J］. Gynecol Obstet Invest， 2000， 50（3）： 178-181. doi：10.1159/000010305 .
[26] SK?LHEGG B S， LANDMARK B F， D?SKELAND S O， et al. Cyclic AMP-dependent protein kinase type I mediates the inhibitory effects of 3'， 5'-cyclic adenosine monophosphate on cell replication in human T lymphocytes［J］. J Biol Chem， 1992， 267（22）： 15707-15714. doi:10.1016/S0021-9258(19)49593-8
[27] KOLODSICK J E， PETERS-GOLDEN M， LARIOS J， et al. Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation［J］. Am J Respir Cell Mol Biol， 2003， 29（5）： 537-544. doi：10.1165/rcmb.2002-0243OC .
[28] LIU X， OSTROM R S， INSEL P A. cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts［J］. Am J Physiol Cell Physiol， 2004， 286（5）： C1089-C1099. doi：10.1152/ajpcell.00461.2003 .
Options
Outlines

/

〈 〉