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Placental syncytin expression in normal and preeclamptic pregnancies

      To the editors:

      Knerr et al
      • Knerr I
      • Beinder E
      • Rascher W.
      Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome.
      recently reported their results on the retroviral syncytin gene expression in placentas, indicating dysregulation in preeclampsia and the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. We recently found similar tendencies while studying syncytin messenger RNA (mRNA) expression in placental extracts by use of both Northern blot analysis and quantitative TaqMan reverse transcriptase (RT)–polymerase chain reaction (PCR) after normalizing the mRNA levels to the GADPH gene (J. C. Keith, Jr, unpublished results). In addition, after measurement of the mRNA levels over various weeks of gestation in apparently normal pregnancies, a progressive increase in syncytin expression was found from the first trimester to term. It is interesting that the level in a 32-week preeclamptic placenta was similar to that found in first-trimester normal placentas (Figure).
      Figure thumbnail gr1
      Syncytin expression in normal and preeclamptic placentas.
      We recently published in situ hybridization and immunohistochemistry results on placental sections showing syncytin mRNA expression in the syncytiotrophoblast covering of the placental villi and syncytin protein localization at the basal surface of the syncytiotrophoblast.
      • Lee X
      • Keith Jr, JC
      • Stumm N
      • Moutsatsos I
      • McCoy JM
      • Crum CP
      • et al.
      Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia.
      In preeclampsia this distribution pattern was disturbed, with a shift in protein localization from basal to apical (microvillous) surfaces of the syncytium. This is not due to an overall reversal of cell polarity, as shown by a correct localization of the transforming growth factor-β receptor endoglin in the syncytiotrophoblast of both normal and preeclamptic placentas. More work is needed for clarifying the mechanisms behind the aberrant expression pattern in preeclampsia.
      Whether transgenic mice might be of use in this particular research, as hinted by Knerr et al, should be considered with caution. Mice do not show the deep trophoblast invasion as seen in the human (R. Pijnenborg, unpublished results), and it is precisely the failure to deeply invade maternal tissues, resulting in impaired placental perfusion, that seems to be the primordial defect in this disease. In addition, the syncytin gene is only present in Old World primates and not in rodents.
      • Voisset C
      • Blancher A
      • Perron H
      • Mandrand B
      • Mallet F
      • Paranhos-Baccala G.
      Phylogeny of a novel family of human endogenous retrovirus sequences, HERV-W, in humans and other primates.
      Of course, this would not preclude searching for other ancient endogenous retroviruses that may have played a role in the evolution of viviparity in different mammalian groups.

      References

        • Knerr I
        • Beinder E
        • Rascher W.
        Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome.
        Am J Obstet Gynecol. 2002; 186: 210-213
        • Lee X
        • Keith Jr, JC
        • Stumm N
        • Moutsatsos I
        • McCoy JM
        • Crum CP
        • et al.
        Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia.
        Placenta. 2001; 22: 808-812
        • Voisset C
        • Blancher A
        • Perron H
        • Mandrand B
        • Mallet F
        • Paranhos-Baccala G.
        Phylogeny of a novel family of human endogenous retrovirus sequences, HERV-W, in humans and other primates.
        AIDS Res Hum Retroviruses. 1999; 15: 1529-1533