Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study.
To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2'-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count), small for gestational age (SGA) fetuses, and intrauterine growth restriction (IUGR) occurring at different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases.
Clinic of Obstetrics and Gynecology, Deparment of Experimental Clinical and Medical Science, University of Udine, Piazzale SM della Misericordia, 15, 33100, Udine, Italy. ambrogio.londero@gmail.com.|Unit of Obstetrics and Gynecology, S. Polo Hospital, 34074, Monfalcone, GO, Italy. ambrogio.londero@gmail.com.
Ambrogio P
AP
Londero
Department of Medical and Biological Sciences, University of Udine, 33100, Udine, Italy.
Maria
M
Orsaria
Department of Medical and Biological Sciences, University of Udine, 33100, Udine, Italy.
Stefania
S
Marzinotto
Clinic of Obstetrics and Gynecology, Deparment of Experimental Clinical and Medical Science, University of Udine, Piazzale SM della Misericordia, 15, 33100, Udine, Italy.
Tiziana
T
Grassi
Frauenklinik, St Franziskus Hospital, Münster, Germany.|Clinic of Obstetrics and Gynecology and Institute of Pathology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Gebäude: A1, 48149, Münster, Germany.
Arrigo
A
Fruscalzo
Clinic of Obstetrics and Gynecology, Deparment of Experimental Clinical and Medical Science, University of Udine, Piazzale SM della Misericordia, 15, 33100, Udine, Italy.
Angelo
A
Calcagno
Department of Surgical Oncology, IRCCS CRO, 33081, Aviano, PN, Italy.
Serena
S
Bertozzi
Department of Medical and Biological Sciences, University of Udine, 33100, Udine, Italy.
Nastassia
N
Nardini
Clinic of Obstetrics and Gynecology, Deparment of Experimental Clinical and Medical Science, University of Udine, Piazzale SM della Misericordia, 15, 33100, Udine, Italy.
Enrica
E
Stella
Clinic of Obstetrics and Gynecology and Institute of Pathology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Gebäude: A1, 48149, Münster, Germany.
Ralph J
RJ
Lellé
Clinic of Obstetrics and Gynecology, Deparment of Experimental Clinical and Medical Science, University of Udine, Piazzale SM della Misericordia, 15, 33100, Udine, Italy.
Lorenza
L
Driul
Department of Medical and Biological Sciences, University of Udine, 33100, Udine, Italy.
Gianluca
G
Tell
Department of Medical and Biological Sciences, University of Udine, 33100, Udine, Italy.
Laura
L
Mariuzzi
D000328:Adult; D016922:Cellular Senescence; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D016209:Interleukin-8 / Q000032:analysis / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
8-OHdG; APE1/Ref-1; IL-6; IL-8; IUGR; Placenta; Preeclampsia; p21; p53