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BOR - Papers in Press, published online ahead of print October 15, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.021139
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biolreprod.103.021139v1
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BIOLOGY OF REPRODUCTION 70, 430–438 (2004)
DOI: 10.1095/biolreprod.103.021139
© 2004 by the Society for the Study of Reproduction, Inc.


Pregnancy

Insulin-Like Growth Factor-I and Binding Proteins 1, 2, and 3 in Bovine Nuclear Transfer Pregnancies1

Susan R. Ravelich3, Bernhard H. Breier2,3, Shiva Reddy4, Jeffrey A. Keelan3, David N. Wells5, A. James Peterson5, and Rita S.F. Lee5

Liggins Institute3 Department of Pediatrics,4 Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand AgResearch,5 Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand

In cloned pregnancies, placental deficiencies, including increased placentome size, reduced placentome number, and increased accumulation of allantoic fluid, have been associated with low cloning efficiency. To assess differences in paracrine and endocrine growth regulation in cloned versus normal bovine placentomes and pregnancies, we have examined the expression of insulin-like growth factor (IGF)-I and -II and their binding proteins (IGFBP)-1 through -3 in placentomes of artificially inseminated (AI), in vitro-produced (IVP), and nuclear transfer (NT) pregnancies at Days 50, 100, and 150 of gestation. Fetal, maternal, and binucleate cell counts in representative placentomes were performed on Days 50–150 of gestation in all three groups. Increased numbers of fetal, maternal, and binucleate cells were present in NT placentomes at all stages of gestation examined. Immunolocalization studies showed that spatial and temporal patterns of expression of IGFBP-2 and -3 were markedly altered in the placentomes of NT pregnancies compared to AI/IVP controls. Concentrations of IGF-I in fetal plasma, as determined by RIA, were significantly higher (P = 0.001) in NT pregnancies (mean ± SEM, 30.3 ± 2.3 ng/ml) compared with AI (19.1 ± 5.5 ng/ml) or IVP (24.2 ± 2.5 ng/ml) pregnancies on Day 150 of gestation. Allantoic fluid levels of IGFBP-1 were also increased in NT pregnancies. These findings suggest that endocrine and paracrine perturbations of the IGF axis may modulate placental dysfunction in NT pregnancies. Furthermore, increased cell numbers in NT placentomes likely have significant implications for fetomaternal communication and may contribute to the placental overgrowth observed in the NT placentomes.

1 Supported by AgResearch and the Health Research Council of New Zealand. AgResearch also provided a Ph.D. stipend to S.R.R.

2 Correspondence: Bernhard Breier, Liggins Institute, University of Auckland, 2-6 Park Ave, Grafton, Auckland, New Zealand. FAX: 0064 9 3737497; bh.breier{at}auckland.ac.nz




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