Gasdermin-D and Pannexin-1 in Pregnancy

Pregnancy Complications Clinical Trial

Official title:

Investigation of Gasdermin-D and Pannexin-1 in Fat and Placental Tissues in Pregnant Women With Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05475951
• Other study ID #: 95932
• Status: Completed
• Phase: N/A
• Start date: December 1, 2021
• Est. completion date: May 30, 2022

Study information

• Verified date: May 2022
• Source: Haseki Training and Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

One -third of fertile women around the world are overweight or obese. This means increasing risk for both the mother and the child. Fat tissue is a factor in gestational DM development and the increase in material inflammation and oxidative stress. According to new knowledge, it is an important need to examine molecules that are not handled in new and human research in these mechanisms in fat and placenta tissues in obesity. For this purpose, the examination of the expression of gasdermin-D and pannex-1 proteins, which are shown to be produced in the cells of both tissues, is worth investigating in human fat tissue and placenta. Gasdermins and pannexins are proteins intersecting by interacting in cellular functions. Gasdermins cause piroptosis, a type of litic proinflammatory cell death. Pannexin-1 plays in various cellular functions, including inflammation. These are examined in a small number of in vitro studies in material fat tissue and placenta, and the design of this study in people whose applications are applied is original in humans. The status of the expressions of the gasdermin-D and pannexin-1 proteins, which will be examined for the first time in obese pregnant women's fat and placental tissues, are the subject of this research with each other and their relationship with other maternal and neonatal data.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: May 30, 2022
• Est. primary completion date: May 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• Being in the 20-35 age range
• Term pregnancy (37-41 weeks)
• Healthy pregnancy follow-up
• Planned cesarean section
• Having no complication in cesarean delivery
• Being a placenta with front or rear walls

Exclusion Criteria:

• Intrauterine surgical procedure
• Presence of prenatal placental structural disorder
• Multiple pregnancies

Related Conditions & MeSH terms

• Maternal Obesity
• Obesity
• Pregnancy Complications

Intervention

Diagnostic Test:
• Biomarker measurement of pannexin-1 and gasdermin-D
These biomarkers were measured in the placental and adipose tissues of the participants.

Locations

Country	Name	City	State
Turkey	Haseki Training and Research Hospital	Sultangazi	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Haseki Training and Research Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (11)

Abrahams VM, Tang Z, Mor G, Guller S. NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells. J Reprod Immunol. 2020 Nov;142:103214. doi: 10.1016/j.jri.2020.103214. Epub 2020 Oct 3. — View Citation

Broz P, Pelegrín P, Shao F. The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2020 Mar;20(3):143-157. doi: 10.1038/s41577-019-0228-2. Epub 2019 Nov 5. Review. — View Citation

Chen KW, Demarco B, Heilig R, Shkarina K, Boettcher A, Farady CJ, Pelczar P, Broz P. Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly. EMBO J. 2019 May 15;38(10). pii: e101638. doi: 10.15252/embj.2019101638. Epub 2019 Mar 22. — View Citation

Dye ZT, Rutledge LV, Penuela S, Dyce PW. Pannexin 1 inhibition delays maturation and improves development of Bos taurus oocytes. J Ovarian Res. 2020 Aug 24;13(1):98. doi: 10.1186/s13048-020-00704-w. — View Citation

Estienne A, Bongrani A, Reverchon M, Ramé C, Ducluzeau PH, Froment P, Dupont J. Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models. Int J Mol Sci. 2019 Sep 9;20(18). pii: E4431. doi: 10.3390/ijms20184431. Review. — View Citation

Korac A, Srdic-Galic B, Kalezic A, Stancic A, Otasevic V, Korac B, Jankovic A. Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. Arch Med Sci. 2021 Feb 26;17(2):323-336. doi: 10.5114/aoms/92118. eCollection 2021. — View Citation

Poston L, Harthoorn LF, Van Der Beek EM; Contributors to the ILSI Europe Workshop. Obesity in pregnancy: implications for the mother and lifelong health of the child. A consensus statement. Pediatr Res. 2011 Feb;69(2):175-80. doi: 10.1203/PDR.0b013e3182055ede. — View Citation

Rancourt RC, Ott R, Ziska T, Schellong K, Melchior K, Henrich W, Plagemann A. Visceral Adipose Tissue Inflammatory Factors (TNF-Alpha, SOCS3) in Gestational Diabetes (GDM): Epigenetics as a Clue in GDM Pathophysiology. Int J Mol Sci. 2020 Jan 12;21(2). pii: E479. doi: 10.3390/ijms21020479. — View Citation

Stubert J, Reister F, Hartmann S, Janni W. The Risks Associated With Obesity in Pregnancy. Dtsch Arztebl Int. 2018 Apr 20;115(16):276-283. doi: 10.3238/arztebl.2018.0276. Review. — View Citation

Tozzi M, Hansen JB, Novak I. Pannexin-1 mediated ATP release in adipocytes is sensitive to glucose and insulin and modulates lipolysis and macrophage migration. Acta Physiol (Oxf). 2020 Feb;228(2):e13360. doi: 10.1111/apha.13360. Epub 2019 Oct 14. — View Citation

Zhang C, Zhao C, Chen X, Tao R, Wang S, Meng G, Liu X, Shao C, Su X. Induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNß from pyroptotic macrophages. Cell Death Dis. 2020 Jun 18;11(6):470. doi: 10.1038/s41419-020-2664-0. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prediction of macrosomy	Prediction of macrosomy will be assesed by meaningfull increases of studied biomarkers Gasdermin-D and Pannexin-1	7 months