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BOR - Papers in Press, published online ahead of print August 11, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.032201
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Submitted May 16, 2004
Returned for revision June 4, 2004
Accepted July 22, 2004

Pregnancy


Altered Placental Lactogen and Leptin Expression in Placentomes from Bovine Nuclear Transfer Pregnancies

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

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

Abstract
Appropriate growth, development and function of the placenta is central to the success of nutrient partitioning between the mother, placenta and fetus. Hormones such as placental lactogen (PL) and leptin are produced in the bovine placenta and play an important role in nutrient partitioning and regulation of placental and fetal growth. Nuclear transfer pregnancies are associated with a number of fetal and placental abnormalities, including increased placental growth and macrosomia, and hence represent a unique situation to gain insight into feto-placental growth regulation. We have examined the expression of bovine PL (bPL) and leptin in placentomes of artificially inseminated (AI), in vitro produced (IVP) and nuclear transfer (NT) pregnancies at days 50, 100 and 150 of gestation in the cow. Immunolocalization studies showed that spatial and temporal patterns of expression of bPL and leptin were markedly altered in the placentomes of NT pregnancies compared to AI or IVP controls. Concentrations of bPL in allantoic fluid, as determined by radioimmunoassay (RIA), were significantly higher (P≤0.001) in NT pregnancies (17.9 ± 3.2 ng/ml; mean ± sd) compared with AI (2.03 ± 1.5 ng/ml), but not IVP (23.4 ± 12.8 ng/ml) pregnancies on d150 of gestation. In contrast, amniotic fluid levels of bPL were significantly decreased in NT pregnancies at d150 gestation. Leptin mRNA expression, as determined by real-time RT-PCR, was increased 2.4-3.0 fold in NT placentomes compared to AI controls, at all gestational ages examined. We speculate that the observed dysregulation of expression of bPL and leptin in NT placentomes could contribute to aberrations in cell migration and invasion and subsequently to alterations in placental metabolism and transfer of nutrients to the fetus, thus leading to increased placental and fetal macrosomia in NT pregnancies.

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


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