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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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Susan R. Ravelich
Bernhard H. Breier
Shiva Reddy
Jeffrey A. Keelan
David N. Wells
A. James Peterson
Rita S.F. Lee
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Submitted July 13, 2003
Returned for revision July 28, 2003
Accepted October 1, 2003

Pregnancy


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

Susan R. Ravelich , Bernhard H. Breier *, Shiva Reddy , Jeffrey A. Keelan , David N. Wells , A. James Peterson , and Rita S.F. Lee

* To whom correspondence should be addressed. E-mail: bh.breier{at}auckland.ac.nz.

Abstract
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 factors-I and -II (IGF-I and -II) and their binding proteins 1-3 (IGFBP-1-3) 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 determined by radioimmunoassay (RIA), were significantly higher (P=0.001) in NT pregnancies (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 are likely to have significant implications for feto-maternal communication, and may contribute to the placental overgrowth observed in the NT placentomes.

Key words: Female Reproductive Tract • Pregnancy • Cytokines • Growth factors • Placenta


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