In baboons as in humans, the placenta is a source of various peptides, including pregnancy-associated plasma protein-A (PAPP-A). However, our present understanding of the regulation of PAPP-A production is incomplete. We have demonstrated that after fetectomy, the baboon placenta retains steroidogenic capacity and is maintained in utero until delivered spontaneously close to term. We have suggested, therefore, that fetectomy provides a valuable in vivo approach to elucidating the role(s) of the fetus, and of the hormones (e.g., estrogen and progesterone) dependent upon the presence of the fetus, in the regulation of placental steroidogenesis during primate pregnancy. Therefore in the present study we utilized the fetectomy model to evaluate the respective roles of the fetus, estrogen, and progesterone on placental PAPP-A. Estradiol, progesterone, and PAPP-A concentrations were determined by RIA in maternal blood collected under ketamine anesthesia on Days 78-100 (n = 5), Days 102-144 (n = 4), and Days 146-164 (n = 3) of gestation (term = Day 184) in control baboons (Papio anubis) and on Days 110-164 in baboons fetectomized on Day 100 (n = 3). Studies were also conducted in five animals in which placental estrogen was increased by maternal treatment on Days 70-100 with androstenedione and in three animals treated on Days 140-164 with the antiestrogen, ethamoxytriphetol (MER-25; 25 mg/day/kg BW). PAPP-A levels were analyzed by ANOVA and Duncan's multiple range test and were compared with placental wet weight (g) previously determined on Day 100 (78 +/- 5) and on Day 165 (171 +/- 6) in untreated baboons; on Day 100 in androstenedione-treated baboons (79 +/- 3); and on Day 165 in antiestrogen-treated (188 +/- 8) and fetectomized (93 +/- 24) baboons. Mean (+/- SE) serum estradiol concentrations (ng/ml) were greater on Day 164 (2.5 +/- 1.0) than on Day 100 (1.0 +/- 0.3), increased on Day 100 by administration of androstenedione (4.8 +/- 1.6), and decreased on Day 165 by fetectomy (0.12 +/- 0.01). Serum progesterone exhibited no significant rise or fall during the second half of gestation and averaged 10.3 +/- 1.4 ng/ml. Concentrations of progesterone late in gestation were reduced (P <0.05) by treatment with MER-25 (3.1 +/- 0.5) and by fetectomy (1.5 +/- 0.2). PAPP-A (mIU/L) increased (p <0.05) throughout the second half of gestation from a mean (+/- SE) of 32.2 +/- 6.2 on Day 78 to 94.5 +/- 11.6 on Days 160-164. Prior to fetectomy, PAPP-A on Days 36-100 (56.1 +/- 5.0) was similar to the corresponding values in controls. However, after fetectomy, serum PAPP-A did not continue to increase with advancing gestation: the mean concentration in the 4-day interval prior to delivery (69.9 +/- 7.9 mlU/L) was lower (p <0.05) than that in the intact controls (94.5 +/- 11.6 mIU/L) but was not different from that measured before fetectomy on Day 100. When expressed relative to placental weight, however, PAPP-A levels in fetectomized baboons at term were comparable to those in untreated controls. PAPP-A was not altered by treatment with androstenedione or MER-25 and was not detectable (less than or equal to 12.2 mIU/L) after delivery of the placenta.Collectively, these findings indicate that production of PAPP-A during baboon pregnancy is determined in large part by the mass of functioning trophoblast and/or by factors that regulate growth of the trophoblast and is not regulated by estrogen or progesterone. In addition, we suggest that the present demonstration of continued secretion of PAPP-A, and the previously documented capacity for aromatization of androgens to estrogen after fetectomy, confirm the viability of the placenta as well as the value of this in vivo animal model for the study of fetoplacental function during primate pregnancy.
Pepe, G. J., Waddell, B., Sinosich, M. J., & Albrecht, E. D. (1994). Influence of fetectomy on serum pregnancy-associated plasma protein-A concentrations in the baboon. Biology of Reproduction, 50, 452-448. https://doi.org/10.1095/biolreprod50.2.442