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Hum. Reprod. Advance Access originally published online on September 14, 2007
Human Reproduction 2007 22(11):2814-2823; doi:10.1093/humrep/dem284
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Histochemical and morphological examination of proliferation and apoptosis in human first trimester villous trophoblast

Manisha Kar, Debabrata Ghosh and Jayasree Sengupta1

Department of Physiology, All India Institute of Medical Sciences, New Delhi 110029, India

1 Correspondence address. Tel: +91-11-2659-4625; Fax: +91-11-2658-8641/2658-8663; E-mail: jsen47{at}gmail.com

BACKGROUND: Our present knowledge about trophoblast turnover in human first trimester placental villi based on multiparametric examination of proliferation and apoptosis is limited.

METHODS: Human villous placentae collected during 6, 7 and 8 weeks (n = 10/each group) of gestation were examined for trophoblast proliferation and apoptosis based on quantitative analyses of immunopositive Fas, tumor necrosis factor receptor 1 (TNFR1), cytokeratin 18 fragment (18f), number of proliferating cell nuclear antigen (PCNA), Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive nuclei, scores of mitotic and apoptotic indices and ultrastructural characteristics.

RESULTS: Mitotic index in cytotrophoblast higher (P < 0.05) at 6 week compared with 7 and 8 weeks of gestation showed significant (P < 0.05) negative correlation between its prevalence and gestational age. Syncytiotrophoblast exhibited higher number of TUNEL positive nuclei (P < 0.01), TUNEL positive apoptotic nuclei (P < 0.05) and apoptotic index (P < 0.05) compared with cytotrophoblast at same gestational age. Positive correlations found between cytokeratin 18f and apoptotic index (P < 0.01), Fas and apoptotic index (P < 0.01), TUNEL positive nuclei and apoptotic index (P < 0.05), cytokeratin 18f and Fas (P < 0.01), whereas cytokeratin 18f (P < 0.05) and Fas (P < 0.05) showed positive correlation only with TUNEL positive apoptotic nuclear data. Phalangeal intrusions of syncytiotrophoblast between transitional cytotrophoblasts showed apposed plasma membranes bearing thickened membrane leaflets, inter-membranous gaps enclosing membranous invaginations, liposome-like particles; patches of membrane seen to be dissolved resulting in cytoplasmic continuity typical of syncytial formation.

CONCLUSION: Cellular remodeling of first trimester villous placenta requires a complex homeodynamics involving proliferation in cytotrophoblast, development-associated syncytialization and apoptosis in syncytiotrophoblast.

Key words: apoptosis/cytotrophoblast/syncytial formation/proliferation/syncytiotrophoblast

Submitted on May 15, 2007; resubmitted on July 31, 2007; accepted on August 17, 2007.


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