Selin DEMİRER, Meryem HOCAOĞLU, Bilge ÖZSAİT SELÇUK, Abdulkadir TURGUT, Evrim KÖMÜRCÜ BAYRAK

Sağlıklı gebeliklerde fetal cinsiyet ile mikro RNA'ların ifade düzeyleri arasındaki ilişki

SAĞLIKLI GEBELİKLERDE FETAL CİNSİYET İLE MİKRORNA'LARIN İFADE DÜZEYLERİ ARASINDAKİ İLİŞKİÖzetAmaç: Sağlıklı gebelikte maternal kan ve plasentaya özgü miRNA’ların araştırılması, maternal/fetal biyolojik ve fizyolojik süreçlerin anlaşılmasına yardımcı olmaktadır. Fetüste dişi ve erkek cinsiyet arasındaki hormonal ve genetik farklılıkların sonucu olarak miRNA ifade düzeyleri değişmektedir. Bu çalışmada amacımız, aday olarak belirlediğimiz miRNA-21-3p, miRNA-155-5p, miRNA-518b ve miR-16-5p ifade düzeylerinin sağlıklı gebelerde fetal cinsiyet ile ilişkisinin araştırılmasıdır.Gereçler ve Yöntem: Çalışma grubu, Kasım 2017 – Mart 2018 tarihlerinde İstanbul Medeniyet Üniversitesi Göztepe Eğitim ve Araştırma Hastanesi Kadın Hastalıkları ve Doğum Kliniğinde gebeliği takip edilen, maternal ve/veya fetal hastalık saptanmayan sağlıklı 21 gebeden oluşmaktadır. Maternal kan örnekleri aynı gebelerin 29. (Grup 1) ve 37. gebelik (Grup 2) haftalarındaki takiplerinde alınmıştır. Maternal kan lökositlerinden RNA izolasyonunun ardından miR-21-3p, miR-155-5p, miR-518b ve miR-16-5p anlatım düzeyleri, SYBR-Green gerçek zamanlı kantitatif PCR ile belirlenmiştir. Gruplar ve fetal cinsiyetler arasındaki miRNA ifade düzeyleri istatistiksel olarak karşılaştırılmıştır.Bulgular: Grup 1 ve Grup 2’de fetal cinsiyet ile klinik ve biyokimyasal parametreler arasında istatistiksel olarak anlamlı bir fark bulunmasa da (p>0,05) miRNA ifade düzeyleri ilişkili bulunmuştur. Buna göre, kız fetüs taşıyan gebelerde erkek fetüs taşıyanlara oranla 29. haftada miR-16-5p (p=0,01) ifade düzeyinin artmış olduğu belirlenmiştir. Erkek fetüs taşıyan gebelerde ise kız fetüs taşıyanlara oranla 37. haftada miR-21-3p (p=0,02), miR-155-5p (p=0,08) ve miR-518b (p=0,02) ifade düzeylerinin artmış olduğu saptanmıştır. Sonuç: İlk defa bu çalışmada, sağlıklı gebelikte maternal kandaki lökositlerde üçüncü trimesterin başında ve sonunda fetal cinsiyet ile değişen miRNA ifade düzeylerinin olduğu gösterilmiştir.

Anahtar Kelimeler:

Gebelik, fetüs, miRNA, lökositler, cinsiyet

RELATIONSHIP BETWEEN FETAL SEX AND THE EXPRESSION LEVELS OF MICRORNAS IN HEALTHY PREGNANCIES

RELATIONSHIP BETWEEN FETAL SEX AND THE EXPRESSION LEVELS OF MICRORNAS IN HEALTHY PREGNANCIESObjective: Differences in microRNA (miRNA) expression in maternal blood and placenta can help us further understand maternal and fetal biology and physiology. Fetal sex differences in miRNA expression are a result of both hormonal and genetic differences between the sexes. The aim of this study was to evaluate the relationship between the expression levels of miRNA-21-3p, miRNA-155-5p, miRNA-518b and miR-16-5p and fetal sex. Materials and Methods: This study was carried out at the Department of Obstetrics and Gynecology of Istanbul Medeniyet University, Goztepe Research and Training Hospital. Twenty-one healthy pregnant women, who were having their pregnancy care through outpatient setting between November 2017 and March 2018, were included in the study. Maternal peripheral blood samples were obtained from the same healthy pregnant females at 29 weeks of gestation (Group 1) and at 37 weeks of gestation (Group 2). The maternal blood leucocyte levels of miRNAs (miRNA-21-3p, miRNA-155-5p, miRNA-518b and miR-16-5p were analyzed using SYBR-Green real-time quantitative polymerase chain reaction. The expression levels of miRNAs between groups and fetal sexes were analyzed statistically.Results: There were no significant differences in clinical and laboratory characteristics between fetal sex in Group 1 and Group 2 (p> 0,05). There was a significant increase in the expression levels of miR-16-5p (p=0,01) in pregnant women with female offspring, compared to the pregnant with male offspring at 29 weeks of gestation. There were significant increases in the expression levels of miR-21-3p (p=0,02), miR-155-5p (p=0,08), miR-518b (p=0,02) in pregnant women with male offspring, compared to the pregnant with female offspring at 37 weeks of gestation. Conclusion: For the first time, in this study were shown to have differential expression levels of maternal blood leukocyte miRNAs between the fetal sexes at the beginning and end of the third trimester.

Keywords:

Pregnancy, fetus, miRNA, leukocyte, sex,

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