Mouse Model Study: Early Life Chronic Stress Effects on Sox2 and Bcl2 mRNA Expression in Gastrointestinal Tissues

Year 2025, Volume: 26 Issue: 1, 42 - 48, 20.03.2025

Keziban Korkmaz Bayram , Aida Nurul Barokah , Merve Hilal Dönmez , Tuba Dilay Ünal , Arslan Bayram

https://doi.org/10.69601/meandrosmdj.1591577

Abstract

Objective: Early-life chronic stress can impact the gastrointestinal (GI) tract and increase cancer risk. Studies on mouse models have shown that maternal stress can cause lasting changes in offspring's physiology and behaviour. These changes can be observed in the GI tract, where disturbances in cellular processes, such as apoptosis, can occur. This study examined mRNA expression in the GI tissues of maternally stressed mice, focusing on Sox2 and Bcl2 mRNA expressions.
Materials and Methods: Pregnant Balb/c mice were randomly divided into three groups. The litters of the control were exposed to routine conditions. In contrast, others were randomly exposed to unpredictable maternal separation (MS) for three hours every day between 1-14 postnatal days (PND). Half of the MS dams were exposed to unpredictable maternal stress (MSUS) within these three hours. Five-week-old litters were sacrificed, and total RNA was isolated from the muscle, duodenum, and stomach tissues using the Phenol-Chloroform technique. Sox2, Bcl2 and Gapdh, mRNA expression was measured by Rotor-Gene Q. The data obtained were analysed using One-Way ANOVA tests and Kruskal-Wallis in GraphPad Prism9.
Results: Although the Bcl2 mRNA expression in the stomach remained unchanged, it significantly increased in the duodenum of MS (p=0.0132). Similarly, while the Sox2 mRNA expression in muscle did not change substantially, it increased significantly in gastric tissue of MSUS (p=0.0030). Furthermore, a significant positive correlation was found between the Sox2 and Bcl2 genes in gastric tissue (p=0.005).
Conclusion: Early life stress, GI dysfunction, and cancer susceptibility may be intricately linked. Understanding the molecular mechanisms involved in cancer susceptibility may have new implications for developing interventions that can reduce the risk of developing cancer. This research may also provide insights into new strategies for treating cancer in predisposed individuals.

Keywords

Maternal Separation, Maternal Stress, Sox2, Apoptosis, Bcl2

Project Number

No funding was received for conducting this study.

Fare Modeli Çalışması: Erken Dönem Kronik Stresin Gastrointestinal Dokularda Sox2 ve Bcl2 mRNA Ekspresyonuna Etkileri

Abstract

Giriş: Yaşamın erken dönemlerinde maruz kalınan kronik stres, gastrointestinal sistem (GI) dahil olmak üzere çeşitli fizyolojik sistemler üzerinde önemli etkilere sahip olabilir ve hatta ilerleyen dönemlerde kanser riskini artırabilir. Fare modelleri üzerinde yapılan çalışmalarda, anneleri strese maruz kalmış yavruların fizyolojisinde ve davranışlarında uzun süreli değişikliklerin oluştuğu gösterilmiştir. Bu çalışmanın amacı, erken dönemde maternal strese maruz kalmış farelerin gastrointestinal dokularında Sox2 ve Bcl2 genlerinin mRNA ifadelerini araştırmaktır.
Yöntem: Balb/c ırkı gebe fareler doğum yapar yapmaz rasgele olarak üç gruba ayrılmıştır. Kontrol grubunun yavruları rutin koşullara maruz bırakılırken, diğer iki grup rastgele olarak günde üç saat boyunca, doğum sonrası (PND) 1-14 günleri arasında öngörülemeyen anne ayrılığına (MS) maruz bırakılmıştır. MS grubu annelerin bir kısmı ise, bu üç saatin içerisinde kısıtlama stresi ve zorunlu yüzme testi aracılı öngörülemeyen anne stresine (MSUS) maruz bırakılmıştır. Yavrular beşinci haftada sakrifiye edilerek kas, duodenum ve mide dokularından Fenol-Kloroform tekniğiyle total RNA izole edilmiştir. Sox2, Bcl2 ve Gapdh, genlerinin mRNA ifade seviyeleri, Rotor-Gene Q Real-Time PCR cihazı kullanılarak ölçülmüştür. Elde edilen veriler GraphPad Prism9 programında One-Way ANOVA testleri ve Kruskal-Wallis kullanılarak analiz edilmiştir.
Bulgular: Mide dokusunda Bcl2 mRNA ifadesi gruplar arasında değişmezken, duodenumda MS grubunda anlamlı olarak artmıştır (p=0,0132). Benzer şekilde, kas dokusundaki Sox2 mRNA ekspresyon seviyesi gruplar arasında önemli ölçüde değişmezken, mide dokusunda MSUS grubunda anlamlı şekilde artmıştır (p=0,0030). Ayrıca, mide dokusunda Sox2 ve Bcl2 genleri arasında anlamlı pozitif korelasyon tespit edilmiştir (p=0005).
Sonuç: Erken yaşam stresi, GI disfonksiyonu ve kansere yatkınlık karmaşık bir şekilde bağlantılı olabilir. Kansere yatkınlık ile ilgili moleküler mekanizmaların anlaşılması, kansere yakalanma riskini azaltabilecek müdahaleler geliştirmek için yeni çıkarımlar ortaya koyabilir. Bu araştırma, kansere yatkın bireylerde kanserle mücadeleye yönelik yeni stratejiler hakkında öngörü sağlayabilir.

Keywords

Anne Ayrılığı, Maternal Stres, Sox2, Apoptoz, Bcl2

Project Number

No funding was received for conducting this study.

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