Abstract
The endocrine mechanisms involved in term and preterm delivery in primates, including pregnant women, are poorly understood. In the term monkey, fetal plasma androgen concentration rises to two hundred times the maternal concentration which remains unchanged. Placental conversion of androgen to estrogen results in increased maternal plasma estrogen concentration at term in both pregnant nonhuman primates and women. In the present study, continuous infusion of androstenedione to 0.8 gestation monkeys resulted in the premature occurrence of labor–type myometrial activity and increases in maternal plasma estrogen, oxytocin and amnion fibronectin concentrations similar to those measured at normal–term labor. Androstenedione induction of these normal–term biochemical and endocrine changes accompanied by fetal membrane rupture, cervical dilatation and live delivery provides a rich opportunity to study the molecular and physiological mechanisms of both term and preterm labor in primates.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Radetsky, P. Stopping premature birth before it's too late. Science 26f6, 1486–1488 (1994).
Buster, J.E. et al. Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. CIS and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, 5-androstenediol, 4-androstenedione, testosterone, and dihydrotestosterone. Am. J. Obstet. Gynecol. 48, 139–142 (1979).
Turnbull, A.C. et al. Significant fall in progesterone and rise in oestradiol levels in human peripheral plasma before onset of labour. Lancet 101–103 (1974).
Mazor, M.R. et al. Human preterm birth is associated with systemic and local changes in progesterone/17β-estradiol ratios. Am. J. Obstet. Gynecol. 171, 231–236 (1994).
Novy, M.J. & Walsh, S.W. Regulation of fetoplacental steroidogenesis in rhesus macaques. in Fetal Endocrinology (eds. Novy, MJ. & Resko, J.A.) 66–94 (Academic Press, New York, 1981).
Challis, J.R.G. et al. The concentrations of progesterone, estrone and estradiol-17β in the peripheral plasma of the rhesus monkey during the final third of gestation, and after induction of abortion with PGF2α . Endocrinology 95, 547 (1974).
Wilson, L., Parsons, M.T. & Flouret, G. Forward shift in the initiation of the nocturnal estradiol surge in the pregnant baboon: Is this the genesis of labor? Am. J. Obstet. Gynecol. 165, 1487–1498 (1991).
Challis, J.R.G. Sharp increase in free circulating oestrogens immediately before parturition in sheep. Nature 229, 208 (1971).
Taylor, N.F., Martin, M.C., Nathanielsz, P.W. & Seron-Ferre, M. The fetus determines circadian oscillation of myometrial electromyographic activity in the pregnant rhesus monkey. Am. J. Obstet. Gynecol. 146, 557–567 (1983).
Hsu, H.W., Figueroa, J.P., Honnebier, M.B.O.M., Wentworth, R. & Nathanielsz, P.W. Power spectrum analysis of myometrial electromyogram and intrauterine pressure changes in the pregnant rhesus monkey in late gestation. Am. J. Obstet. Gynecol. 161, 467–473 (1989).
Figueroa, J.P., Honnebier, M.B.O.M., Binienda, Z., Wimsatt, J. & Nathanielsz, P.W. Effect of 48-hour intravenous A4A androstenedione infusion on the pregnant rhesus monkey in the last third of gestation: Changes in maternal plasma estradiol concentrations and myometrial contractility. Am. J. Obstet. Gynecol. 161, 481–486 (1989).
Honnebier, M.B.O.M., Figueroa, J.P., Rivier, J., Vale, W. & Nathanielsz, P.W. Studies on the role of oxytocin in late pregnancy in the pregnant rhesus monkey (I): Plasma concentrations of oxytocin in the maternal circulation throughout the 24 h day and the effect of the synthetic oxytocin antagonist[1-β-Mpaβ-(CH2)5)1′) Me)Tyr2,Orn8] OT on spontaneous nocturnal myometrial contractions. J. Dev. Physiol. 12, 225–233 (1989).
Hirst, J.J., Haluska, G.J., Cook, M.J. & Novy, M.J. Plasma oxytocin concentrations during gestation and the effect of an oxytocin antagonist in pregnant rhesus monkeys. Am. J. Obstet. Gynecol. 164, 252 (1991).
Liggins, G.C., Fairclough, R.J., Grieves, S.A., Kendall, K.Z. & Knox, B.S. The mechanism of initiation of parturition in the ewe. Recent Prog. Norm. Res. 29, 111–149 (1973).
Thomas, A.L., Krane, E.J. & Nathanielsz, P.W. Changes in the fetal thyroid axis after induction of premature parturition by low dose continuous intravascular cortisol infusion to the fetal sheep at 130 days of gestation. Endocrinology 103, 17–23 (1978).
McDonald, T.J. & Nathanielsz, P.W. Bilateral destruction of the fetal paraventricu-lar nuclei prolongs gestation in sheep. Am. J. Obstet. Gynecol. 165, 764–770 (1991).
Magyar, D.M. et al. Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition. Endocrinology 107, 155–159 (1980).
Anderson, A.B.M., Flint, A.P.F. & Turnbull, A.C. Mechanism of action of glucocorticoids in induction of ovine parturition: Effect of placental steroid metabolism. J. Endocrinol. 66, 61–70 (1975).
Siiteri, P.K. & Seron-Ferre, M. Some new thoughts on the fetoplacental unit and parturition in primates. in Fetal Endocrinology (eds. Novy, M J. & Resko, J.A.) 1–34 (Academic Press, New York, 1981).
Walsh, S.W., Stanczyk, F.Z. & Novy, M.J. Daily hormonal changes in the maternal, fetal, and amniotic fluid compartments before parturition in a primate species. J. Clin. Endocrinol Metab. 58, 629–639 (1984).
Challis, J.R.G. et al. Steroids in the amniotic fluid of the rhesus monkey (Macaca mulatta). J. Endocrinol 73, 355–363 (1977).
Nathanielsz, P.W., Honnebier, M.B.O.M. & Figueroa, J.P. In the rhesus monkey placental retention after fetectomy at 121 to 130 days' gestation outlasts the normal duration of pregnancy. Am. J. Obstet. Gynecol. 166, 1529–1535 (1990).
Nathanielsz, P.W. et al. Update on molecular events of myometrial activity during pregnancy. in Research in Perinatal Medicine I (eds. Nathanielsz, P.W. & Parer, J.T.) 887–111 (Perinatology Press, Ithaca, New York, 1984).
Lockwood, C.J. et al. Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. New Engl J. Med. 325, 669–674 (1991).
Challis, J.R.G. et al. The effects of dexamethasone on the peripheral plasma concentrations of androstenedione, testosterone and cortisol in the pregnant rhesus monkey. Endocrinology 96, 185 (1975).
Challis, J.R.G., Robinson, J.S. & Thorburn, G.D. Fetal and maternal endocrine changes during pregnancy and parturition in the rhesus monkey. CIBA Found. Symp. 47, 211 (1977).
Novy, M.J. & Walsh, S.W. Dexamethasone and estradiol treatment in pregnant rhesus macaques: Effects on gestational length, maternal plasma hormones, and fetal growth. Am. J. Obstet. Gynecol 145, 920–931 (1983).
Albrecht, E.D., Crenshaw, M.C., Jr. & Pepe, G.J. The effect of estrogen on placental delivery after fetectomy in baboons. Am. J. Obstet. Gynecol. 160, 237–241 (1989).
Challis, J.R.G., Davies, I.J., Benirschke, K., Hendrickz, A.G. & Ryan, K.J. The effects of dexamethasone on plasma steroid levels and fetal adrenal histology in the pregnant rhesus monkey. Endocrinology 95, 1300–1305 (1974).
Amico, J.A. & Hempel, J. An oxytocin precursor intermediate circulates in the plasma of humans and rhesus monkeys administered estrogen. Neuroendo-crinology 51, 437–443 (1990).
Fuchs, A.R., Periyasamy, S., Alexandrova, M. & Soloff, M.S. Correlation between oxytocin receptor concentration and responsiveness to oxytocin in pregnant rat myometrium: Effects of ovarian steroid. Endocrinology 113, 742–749 (1983).
Miller, F.D., Chibbar, R. & Mitchell, B.F. Synthesis of oxytocin in amnion, chorion and decidua: A potential paracrine role for oxytocin in the onset of human parturition. Reg. Pep. 45, 247–251 (1993).
Wilson, L. Jr., Parsons, M.T. & Flouret, G. Inhibition of spontaneous uterine contractions during the last trimester in pregnant baboons by an oxytocin antagonist. Am. J. Obstet. Gynecol. 163, 1875–1882 (1990).
Zhang, J., Weston, P.G. & Hixon, J.E. Influence of estradiol on the secretion of oxytocin and prostaglandin F2α during luteolysis in the ewes. Biol Reprod. 45, 395–403 (1991).
Garfield, R.E., Kannan, M.S. & Daniel, E.E. Gap junction formation in myometrium: Control of estrogens, progesterone, and prostaglandins. Am. J. Physiol 238C, 81–89 (1980).
Lye, S.E. The initiation and inhibition of labor — toward a molecular understanding. Semin. Reprod. Endocrinol. 12(4), 284–297 (1994).
Tribollet, E., Audigier, S., Dubois-Dauphin, M. & Dreifuss, J.J. Gonadal steroids regulate oxytocin receptors in the brain of male and female rats. An autoradi-ographical study. Brain Res. 511, 129–140 (1990).
Haluska, G.J., Stancyzk, F.Z., Cook, M.J. & Novy, M.J. Temporal changes in uterine activity and prostaglandin response to RU486 in rhesus macaques in late gestation. Am. J. Obstet. Gynecol. 157, 1487–1495 (1987).
Elsner, C.W., Buster, J.E., Preston, D.L. & Killam, A.P. Interrelationship of circulating maternal steroid concentrations in third trimester pregnancies. III. Effect of intravenous cortisol infusion on maternal concentrations of estriol, 16 α-hydroxyprogesterone, 17α-hydroxyprogesterone, progesterone, 20α-dihydroprogesterone, Δ5-pregnenolone, Δ5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol. J. Clin. Endocrinol Metab. 49, 30–33 (1979).
Shozu, M., Akasofu, K., Harada, T. & Kubota, Y. A new cause of female pseudo-hermaphroditism: Placental aromatase deficiency. J. Clin. Endocrinol Metab. 72, 560–566 (1991).
Binienda, Z. et al. Endocrine changes during 48 hours of food withdrawal in the pregnant rhesus monkey in the last third of gestation. J. Clin. Endocrinol Metab. 68, 1184–1188 (1989).
Guller, S., Alien, D.L., Corin, R., Lockwood, C.J. & Sonenberg, M. Growth hormone and fibronectin expression in 3T3 preadipose cells. Endocrinology 130, 2609–2616 (1992).
Guller, S. et al. Glucocorticoid suppression of human placental fibronectin expression: implications in uterine-placental adherence. Endocrinology 133, 1139–1146 (1993).
Sedmak, JJ. & Grossberg, S.E. A rapid and versatile assay for protein using Coomassie brilliant blue G-250. Anal Biochem. 79, 544–552 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mecenas, C., Giussani, D., Owiny, J. et al. Production of premature delivery in pregnant rhesus monkeys by androstenedione infusion. Nat Med 2, 443–448 (1996). https://doi.org/10.1038/nm0496-443
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nm0496-443
This article is cited by
-
Association between fetal sex and pregnancy outcomes among women with twin pregnancies: a multicenter cross-sectional study
Archives of Gynecology and Obstetrics (2022)
-
Local paracrine effects of estradiol are central to parturition in the rhesus monkey
Nature Medicine (1998)