ORİJİNAL ARAŞTIRMALAR
Yüksek Yağlı Diyetin Epigenetik Etkisinin Araştırılması: Fare Ovaryumunda Dnmt3b ve Dnmt3l Ekspresyonu
Unraveling the Epigenetic Impact of High-Fat Diet: Dnmt3b and Dnmt3l Expressions in Mouse Ovary
Received Date : 14 Aug 2023
Accepted Date : 25 Aug 2023
Available Online : 31 Aug 2023
Fatma UYSALa, Nazlıcan BOZDEMİRa, Tuba KABLANa, Gözde ŞÜKÜRb,
Meltem SÖNMEZERc, Özgür ÇINARb,d
aDepartment of Histology and Embryology, Ankara Medipol University Faculty of Medicine, Ankara, Türkiye
bDepartment of Histology and Embryology, Ankara University Faculty of Medicine, Ankara, Türkiye
cPrivate Physician, Ankara, Türkiye
dCenter for Assisted Reproduction, Ankara University Faculty of Medicine, Ankara, Türkiye
Doi: 10.24074/tjrms.2023-99067 - Makale Dili: EN
TJRMS. 2023;7(2):61-7
ÖZET
Amaç: Obezite, yağ dokusu hacmindeki artış ile karakterizedir. İnfertilite için önemli bir risk faktörü olarak görülmektedir. Son araştırmalar, obezite
ve epigenetik arasında güçlü bir ilişki olduğunu göstermektedir. Başta DNA metiltransferazlar tarafından katalizlenen DNA metilasyonu
olmak üzere epigenetik mekanizmalar gen ekspresyonunu düzenlerler. Bu çalışmada, YYD ile indüklenen grubun ovaryumlarında Dnmt3b ve
Dnmt3l ekspresyonunu kontrol ile karşılaştırmalı olarak değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bu amaçla, C57BL6/J dişi fareler (4
haftalık) (n=8) %20 protein, %10 yağ ve %70 karbonhidrattan oluşan normal bir diyetle veya %20 protein, %20 karbonhidrat ve %60 yağdan oluşan
bir YYD ile 12 hafta boyunca beslendi. 12 haftanın sonunda hayvanlara ötenazi yapıldı ve ovaryumlar tamponlu solüsyona aktarıldı. Araştırma
hedefimize uygun olarak, YYD ile indüklenen farelerin ovaryumlarındaki Dnmt3b ve Dnmt3l proteinlerinin varlığını ve değişikliklerini
incelemek için immünohistokimya tekniğini kullandık. Bulgular: Bulgularımız, YYD'in neden olduğu obez farelerin ovaryumlarındaki protein
seviyelerinde önemli değişiklikler olduğunu ortaya koydu. Spesifik olarak, hem Dnmt3b hem de Dnmt3l'nin toplam ekspresyonları, YYD grubunun
ovaryumlarında önemli ölçüde arttı (p<0.05). Ayrıca YYD ile indüklenen grupta, folikülogenezin her aşamasında Dnmt3b ekspresyonunda
artış gözlenirken, granüloza hücrelerinde Dnmt3b ve Dnmt3l ekspresyonlarında artış gözlendi (p<0.05). Sonuç: Bu sonuçlar YYD’in
özellikle granüloza hücrelerinde önemli bir etkiye sahip olduğunu göstermiş olup, ovaryumlardaki Dnmt3b ve Dnmt3l ekspresyon seviyelerindeki
artışın daha önceki çalışmamızda gösterdiğimiz artan global DNA metilasyonu ile potansiyel olarak ilişkilendirilebilir olması bakımından
önemlidir.
Anahtar Kelimeler: Dnmt3b; Dnmt3l; obezite; oogenez; ovaryum
ABSTRACT
Objective: Obesity is characterized by an increase in adipose tissue volume. It has emerged as a risk factor for infertility. Recent research has
unveiled a strong correlation between obesity and epigenetics. Epigenetic mechanisms, primarily DNA methylation which is governed by DNA
methyltransferases (Dnmts), regulates gene expression. In the present study, we aimed to evaluate Dnmt3b and Dnmt3l expression in ovary of
HFD-induced group compared to control. Materials and Methods: For this purpose, C57BL6/J female mice (4 weeks old) (n=8) were fed either
a normal diet consisting of 20% protein, 10% fat and 70% carbohydrate or an HFD consisting of 20% protein, 60% fat and 20% carbohydrate
for 12 weeks. At the end of 12 weeks, animals were euthanized, and ovaries were transferred into buffered solution. In accordance with our
research objective, we conducted immunohistochemistry to examine the presence of Dnmt3b and Dnmt3l proteins and their changes in the ovaries
of HFD-induced mice. Results: Our findings revealed significant alterations in the protein levels in the ovary of the HFD-induced obese mice.
Specifically, the total expressions of both Dnmt3b and Dnmt3l were remarkably increased in the ovary of the HFD group (p<0.05). Furthermore,
we observed increased expression of Dnmt3b in each stage of folliculogenesis, while Dnmt3b and Dnmt3l expressions were elevated in granulosa
cells of the HFD-induced group (p<0.05). Conclusion: These results indicate that HFD has a significant impact on the expression of Dnmt3b
and Dnmt3l proteins in the ovaries, particularly affecting granulosa cells, which could be potentially associated with the observed changes in global
DNA methylation levels.
Keywords: Dnmt3b; Dnmt3l; obesity; oogenesis; ovary
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