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Serum Leptin Concentrations and Expression of Leptin Transcripts in Placental Trophoblast with Advancing Baboon Pregnancy¹

Departments of Obstetrics/Gynecology (M.C.H., J.S.O., K.F.S., W.S.), Physiology (M.C.H., W.S.), and Anatomy (M.C.H.) and the Interdisciplinary Program in Molecular and Cellular Biology (M.C.H., J.S.O., A.E.G.), Tulane University School of Medicine, New Orleans, Louisiana 70112-2699; Tulane Regional Primate Research Center (M.C.H.), Covington, Louisiana 70433-8915; and the Department of Obstetrics/Gynecology, Texas Tech University Health Sciences Center (V.D.C., T.G.), Amarillo, Texas 79106-1797

Address all correspondence and requests for reprints to: Michael C. Henson, Ph.D., Department of Obstetrics/Gynecology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112-2699. E-mail: michael.henson{at}tulane.edu

Leptin is a polypeptide hormone originally thought to be produced exclusively by adipocytes. Recently, however, both leptin messenger ribonucleic acid (mRNA) and leptin protein were identified in human placental trophoblast cells, suggesting a potential role in primate pregnancy. In the present study, venous blood samples were collected at 5-day intervals during gestation from baboons (Papio sp), an established model for the study of human pregnancy, as well as from nonpregnant baboons, and leptin concentrations were determined by RIA. Additionally, placental villous tissue was collected upon cesarean delivery at early (days 60–62; n = 5), mid (days 98–102; n = 5), and late (days 159–167; n = 5) gestation (term = 184 days), and leptin mRNA was quantitated by competitive RT-PCR. Finally, in situ hybridization was employed to localize transcripts to specific placental cell types. Results determined that maternal leptin levels (mean ± SEM), which were dramatically greater (P < 0.01) than those in nonpregnant cycling baboons (1.4 ± 0.1 ng/mL), increased (P < 0.005) with gestational age from 63.6 ± 10.4 ng/mL on day 60 of gestation to 157.8 ± 16.1 near term. Levels declined to those found in cycling baboons by 15 days postdelivery. In contrast to maternal leptin concentrations, placental leptin mRNA decreased (P < 0.02) with advancing pregnancy, as transcript abundance declined approximately 8-fold from early to late gestation. Maternal peripheral leptin concentrations were positively correlated (r = 0.66; P < 0.001) whereas placental leptin mRNA levels were negatively correlated (r = -0.64; P < 0.01) with gestational age. Expression of leptin mRNA transcripts, as evidenced by RT-PCR in villous tissue, was localized principally within syncytiotrophoblast by in situ hybridization.

In summary, changes in maternal peripheral leptin concentrations and placental leptin mRNA abundance that occur commensurate with advancing gestational age may imply evolving roles for the polypeptide with advancing primate pregnancy. In this capacity, localization of leptin transcripts within the baboon syncytiotrophoblast suggests the potential for autocrine or paracrine interactions within this endocrinologically active tissue. Finally, both the similarities in leptin ontogeny in baboon and human pregnancy and the singular enhancement of maternal leptin levels inherent throughout baboon gestation emphasize the potential of this nonhuman primate model for the study of leptin action in the maternal-fetoplacental unit.

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