This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, J. T. Articles by Waddell, B. J. Search for Related Content PubMed PubMed Citation Articles by Smith, J. T. Articles by Waddell, B. J.

Leptin Distribution and Metabolism in the Pregnant Rat: Transplacental Leptin Passage Increases in Late Gestation but Is Reduced by Excess Glucocorticoids

School of Anatomy and Human Biology and the Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Perth, Western Australia, 6009, Australia

Address all correspondence and requests for reprints to: Dr. Brendan Waddell, School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia. E-mail: bwaddell{at}anhb.uwa.edu.au.

Leptin is essential for the establishment of pregnancy and appears to promote fetal growth, but the mechanisms regulating fetal leptin exposure remain unclear. In rodents, indirect evidence suggests that fetal leptin is partly derived from the maternal circulation via transplacental passage. Indeed, the placenta expresses mRNA for Ob-Ra, one of the short forms of the leptin receptor (Ob-R_S) important in leptin transport, and this expression increases markedly in late pregnancy. Therefore, we determined the transplacental passage of maternal leptin to the fetus in the rat and whether this transport increases near term in association with a rise in placental expression of Ob-R_S protein. Because of the proposed role of leptin in promoting fetal growth, we also assessed the effect of glucocorticoid-induced fetal growth retardation on placental leptin transport. Anesthetized rats received a constant infusion of ¹²⁵I-leptin via a jugular cannula before and at d 16 and 22 of pregnancy (term = d 23); plasma samples were obtained at 10, 20, 40, 60, 80, and 100 min, and fetuses and placentas were collected at the time of the final sample. The metabolic clearance rate of leptin fell (P < 0.01) from 3.08 ± 0.23 ml/min per kg in nonpregnant rats to 2.36 ± 0.13 ml/min per kg by d 22. Transplacental passage of ¹²⁵I-leptin, estimated from its concentration in the whole fetus relative to maternal plasma, increased 10-fold (P < 0.005) between d 16 and d 22 of pregnancy. Over this same period, Ob-R_S protein expression in the placental labyrinth zone increased by almost 2-fold. Transplacental leptin passage was reduced (P < 0.05) by 77% after maternal dexamethasone treatment, whereas suppression of endogenous glucocorticoid synthesis (by metyrapone) increased (P < 0.05) the transfer of maternal leptin to the fetus by 55%. These data show that transplacental passage of maternal leptin is a significant source of fetal leptin and increases markedly during late pregnancy. Consistent with the proposed role of leptin as a fetal growth factor, transplacental leptin passage is reduced in association with glucocorticoid-induced fetal growth retardation.

This article has been cited by other articles:

				A. Jelks, L. Belkacemi, Guang Han, W.-L. Chong, M. G. Ross, and M. Desai Paradoxical Increase in Maternal Plasma Leptin Levels in Food-Restricted Gestation: Contribution by Placental and Adipose Tissue Reproductive Sciences, July 1, 2009; 16(7): 665 - 675. [Abstract] [PDF]

				P. J. Mark, S. Augustus, J. L. Lewis, D. P. Hewitt, and B. J. Waddell Changes in the Placental Glucocorticoid Barrier During Rat Pregnancy: Impact on Placental Corticosterone Levels and Regulation by Progesterone Biol Reprod, June 1, 2009; 80(6): 1209 - 1215. [Abstract] [Full Text] [PDF]

				H. Chen, D. Simar, K. Lambert, J. Mercier, and M. J. Morris Maternal and Postnatal Overnutrition Differentially Impact Appetite Regulators and Fuel Metabolism Endocrinology, November 1, 2008; 149(11): 5348 - 5356. [Abstract] [Full Text] [PDF]

				A. J. Forhead, C. A. Lamb, K. L. Franko, D. M. O'Connor, F. B. P. Wooding, R. L. Cripps, S. Ozanne, D. Blache, Q. W. Shen, M. Du, et al. Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestation J. Physiol., May 1, 2008; 586(9): 2393 - 2403. [Abstract] [Full Text] [PDF]

				C. J. Stocker, E. Wargent, J. O'Dowd, C. Cornick, J. R. Speakman, J. R. S. Arch, and M. A. Cawthorne Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1810 - R1818. [Abstract] [Full Text] [PDF]

				D. P. Hewitt, P. J. Mark, and B. J. Waddell Glucocorticoids Prevent the Normal Increase in Placental Vascular Endothelial Growth Factor Expression and Placental Vascularity during Late Pregnancy in the Rat Endocrinology, December 1, 2006; 147(12): 5568 - 5574. [Abstract] [Full Text] [PDF]

				B. E Levin Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis Phil Trans R Soc B, July 29, 2006; 361(1471): 1107 - 1121. [Abstract] [Full Text] [PDF]

				I C McMillen, L J Edwards, J Duffield, and B S Muhlhausler Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction, March 1, 2006; 131(3): 415 - 427. [Abstract] [Full Text] [PDF]

				M. C. Henson and V. D. Castracane Leptin in Pregnancy: An Update Biol Reprod, February 1, 2006; 74(2): 218 - 229. [Abstract] [Full Text] [PDF]

				I. C. McMillen, C. L. Adam, and B. S. Muhlhausler Early origins of obesity: programming the appetite regulatory system J. Physiol., May 15, 2005; 565(1): 9 - 17. [Abstract] [Full Text] [PDF]

				I. C. Mcmillen and J. S. Robinson Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming Physiol Rev, April 1, 2005; 85(2): 571 - 633. [Abstract] [Full Text] [PDF]

				J. T Smith, P. J Mark, and B. J Waddell Developmental increases in plasma leptin binding activity and tissue Ob-Re mRNA expression in the rat J. Endocrinol., March 1, 2005; 184(3): 535 - 541. [Abstract] [Full Text] [PDF]

				D. E. Edwards, R. P. Bohm Jr, J. Purcell, M. S. Ratterree, K. F. Swan, V. D. Castracane, and M. C. Henson Two Isoforms of the Leptin Receptor Are Enhanced in Pregnancy-Specific Tissues and Soluble Leptin Receptor Is Enhanced in Maternal Serum with Advancing Gestation in the Baboon Biol Reprod, November 1, 2004; 71(5): 1746 - 1752. [Abstract] [Full Text] [PDF]

				B.S.J. Yuen, P.C. Owens, M.E. Symonds, D.H. Keisler, J.R. McFarlane, K.G. Kauter, and I.C. McMillen Effects of Leptin on Fetal Plasma Adrenocorticotropic Hormone and Cortisol Concentrations and the Timing of Parturition in the Sheep Biol Reprod, June 1, 2004; 70(6): 1650 - 1657. [Abstract] [Full Text] [PDF]