The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy.
Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7-9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤ 6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤ 6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans.
Hospital Universitario La Fe, Valencia, Spain.
Teresa
T
Lozoya
INCLIVA Biomedical Research Institute, Valencia, Spain.
Francisco
F
Domínguez
Universidad de Córdoba; CIBER Obesidad y Nutrición (CIBERobn) & IMIBIC/HURS, Córdoba, Spain.
Antonio
A
Romero-Ruiz
Universidad de Córdoba; CIBER Obesidad y Nutrición (CIBERobn) & IMIBIC/HURS, Córdoba, Spain.
Liliana
L
Steffani
Fundación Instituto Valenciano de Infertilidad (FIVI) and Instituto Universitario IVI/INCLIVA, Valencia University, Valencia, Spain.
Sebastián
S
Martínez
Hospital Universitario La Fe, Valencia, Spain.
Mercedes
M
Monterde
Hospital Universitario La Fe, Valencia, Spain.
Blanca
B
Ferri
Hospital Universitario La Fe, Valencia, Spain.
Maria Jose
MJ
Núñez
Hospital Universitario La Fe, Valencia, Spain.
AinhoaRomero-Espinós
Hospital Universitario La Fe, Valencia, Spain.
Omar
O
Zamora
Hospital Universitario La Fe, Valencia, Spain.
Marta
M
Gurrea
Universidad de Córdoba; CIBER Obesidad y Nutrición (CIBERobn) & IMIBIC/HURS, Córdoba, Spain.
Susana
S
Sangiao-Alvarellos
Hospital Universitario La Fe, Valencia, Spain.
Olivia
O
Vega
Fundación Instituto Valenciano de Infertilidad (FIVI) and Instituto Universitario IVI/INCLIVA, Valencia University, Valencia, Spain and Department of Obstetrics and Gynecology, School of Medicine, Stanford University, California, United States of America.
Carlos
C
Simón
Hospital Universitario La Fe, Valencia, Spain.
Antonio
A
Pellicer
Universidad de Córdoba; CIBER Obesidad y Nutrición (CIBERobn) & IMIBIC/HURS, Córdoba, Spain.
Manuel
M
Tena-Sempere
D000328:Adult; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human