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Regulation of the Glycosylated ß-Lactoglobulin Homolog, Glycodelin [Placental Protein 14:(PP₁₄)] in the Baboon (Papio anubis) Uterus¹

Departments of Obstetrics and Gynecology, University of Illinois ((H.M.H., K.M.D., H.G.V, A.T.F.) Chicago, Illinois 60612; and University of Leicester (S.C.B.), Leicester, LE2 7LX, United Kingdom

Address all correspondence and requests for reprints to: Asgi T. Fazleabas, The University of Illinois at Chicago, Department of Obstetrics and Gynecology, 820 South Wood Street (M/C 808), Chicago, Illinois 60612-7313. E-mail: asgi{at}uic.edu

Abstract

In vitro studies indicate that glycodelin (PP₁₄) synthesis by the human endometrium increases dramatically at the time of implantation and early pregnancy. It has been postulated that this protein may have an immunosuppressive function. Due to the limitations associated with in vivo studies in the human, this study was undertaken to study the regulation of the baboon glycodelin homolog in vivo during the menstrual cycle and early pregnancy. In nonpregnant baboons, between days 10–12 postovulation (n = 3) the mid and apical regions of the glandular epithelium showed a distinct punctate staining pattern, which increased between days 12–18 of pregnancy (n = 3). Between days 25–60 of pregnancy, staining intensity in the glandular epithelium decreased. The decrease was more apparent at the implantation site compared with the nonimplantation site. The immunostaining correlated with the synthesis of radiolabeled baboon glycodelin in explant culture. Northern blot analysis demonstrated two messenger RNA (mRNA) transcripts [1.0 and 1.7 kilobases (kb)] in the baboon uterus compared with a single 1.0-kb transcript in the human, and mRNA expression was consistent with protein localization and synthesis. The protein and mRNA expression was consistently higher in the deeper glands of the functionalis and basalis during early pregnancy. Because the increased expression of glycodelin in the baboon endometrium coincided with peak levels of CG, a simulated pregnant baboon model was used to confirm hormonal regulation. Exogenous human CG (hCG) followed by estrogen and progesterone treatment in intact and ovariectomized baboons up-regulated glycodelin expression between days 18–25 postovulation (n = 10). By day 32 postovulation (n = 3), glycodelin synthesis decreased. Estrogen and progesterone treatment in the absence of exogenous hCG did not result in an increase of glycodelin synthesis. Analysis of uterine flushings from hCG-treated animals revealed that a minimum of 7 days of hCG treatment was required for glycodelin to be detectable in the uterine lumen. These studies indicate that a posttranslationally modified glycodelin homolog is synthesized by the baboon uterus during early pregnancy and appears to be regulated directly by CG. This pattern of synthesis is comparable with that observed with in vitro studies in the human. Because glycodelin expression is associated with CG secretion, we suggest that this protein may have a functional role during implantation in the primate. Thus, the baboon may serve as a nonhuman primate model to elucidate the function of this protein in vivo.

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