Oosit olgunlaşması ve embriyo gelişimi sırasında PATL2 transkript düzeylerinin zamansal düzenlenmesi: Bir silico analizi

Öz

Amaç: Kadın kısırlığı üreme sisteminin nispeten sık görülen bir bozukluğudur ve moleküler etiyolojisi ve ilişkili hücresel mekanizmaları henüz açıklanamamıştır. PATL2'deki belirli mutasyonların, oosit olgunlaşmasının durması ve oosit meiotik eksikliği ile karakterize edilen kadın kısırlığına yol açtığı belirlenmiştir. PATL2, oosit olgunlaşmasında translasyonel baskılayıcı olarak işlev gören bir RNA bağlayıcı protein kodlar; bu nedenle, PATL2 ekspresyonunun uygun zamansal kontrolünün normal oosit olgunlaşması için elzem olduğu ileri sürülmüştür. Yöntem: Bu çalışmada, R programlama dilini kullanarak, farelerde oosit olgunlaşması ve embriyo gelişimi sırasında PATL2 transkript seviyelerinin zamansal düzenlenmesini analiz etmek için transkriptomik verileri kullanılmıştır. Bulgular: Fare oositlerinde PATL2 geninin mRNA ekspresyonunun primordial folikül aşamasından birincil folikül aşamasına kadar arttığı ve ekspresyonunun birincil ve ikincil folikül aşamalarında yüksek kaldığı, ardından antral folikül aşamalarında (üçüncül folikül aşaması) azaldığı gösterilmiştir. Ayrıca, farelerde PATL2 ekspresyonunun metafaz 2 (MII) aşamasındaki oositlerde germinal vezikül (GV) aşamasındaki oositlere kıyasla daha düşük olduğu ve PATL2 transkript seviyelerinin embriyo gelişimi sırasında bile değiştiği bulunmuştur. Sonuç: Mevcut çalışmadaki veriler, oosit büyümesi sırasında PATL2 ekspresyonunun transkripsiyon seviyesinde zamansal olarak düzenlendiğini ve protein seviyesinde gerçekleştirilen önceki araştırmaları desteklediğini göstermektedir. PATL2'nin oosit matürasyon durması ve dişi kısırlığındaki önemi ve tanımlanan PATL2 patojenik varyantlarının sayısı göz önüne alındığında, oositlerde transkripsiyonel seviyede PATL2 regülasyonunun daha iyi bir mekanistik anlayışı klinik öneme sahip olabilir ve yeni tedavi stratejilerinin geliştirilmesine rehberlik edebilir.

Anahtar Kelimeler

• PATL2 geni
• oosit olgunlaşmasının durması
• oosit büyümesi
• germinal vezikül durması
• sekonder folikül evresi
• kadın doğurganlığı
• gen regülasyonu

Temporal regulation of PATL2 transcript levels during oocyte maturation and embryo development: An in silico analysis

Öz

Objective: Female infertility is a relatively frequent disorder of the reproductive system, and its molecular etiology and associated cellular mechanisms remain unexplained. Certain mutations in PATL2 gene have been identified to cause female infertility, characterized by oocyte maturation arrest and oocyte meiotic deficiency. PATL2 encodes an RNA-binding protein functioning as a translational repressor in oocyte maturation; therefore, proper temporal control of PATL2 expression was suggested to be essential for normal oocyte maturation. Methods: Transcriptomics data was used to analyze temporal regulation of PATL2 transcript levels during oocyte maturation and embryo development in mice, using R programming language. Results: Based on in silico analysis, mRNA expression of the PATL2 gene in mouse oocytes was found to increase from the primordial follicle stage to the primary follicle stage (p ≤ 0.05). Its expression was reported to stay high in the primary and secondary follicle stages, then to decrease in the antral follicle stages (tertiary follicle stages). Besides, PATL2 expression was shown to be lower in metaphase 2 (MII)-stage oocytes compared to germinal vesicle (GV)-stage oocytes in mice (p ≤ 0.05). Moreover, it was observed that PATL2 transcript levels even change during embryo development. Conclusion: Data in the present study points to the temporal regulation of PATL2 expression at the transcription level during oocyte growth, supporting previous research performed at the protein level. Considering the importance of PATL2 in oocyte maturation arrest and female sterility, and also the number of PATL2 pathogenic variants previously identified, a better mechanistic understanding of PATL2 regulation at the transcriptional level in oocytes might have clinical significance and guide the development of novel treatment strategies.

Anahtar Kelimeler

• PATL2 gene
• oocyte maturation arrest
• oocyte growth
• germinal vesicle arrest
• secondary follicle stage
• female fertility
• gene regulation

Kaynakça

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