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Increased placental neurosteroidogenic gene expression precedes poor outcome in the preterm guinea pig

Published online by Cambridge University Press:  10 January 2014

A. L. Cumberland*
Affiliation:
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia Hunter Medical Research Institute, Mothers and Babies Research Centre, Newcastle, New South Wales, Australia
H. K. Palliser
Affiliation:
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia Hunter Medical Research Institute, Mothers and Babies Research Centre, Newcastle, New South Wales, Australia
J. J. Hirst
Affiliation:
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia Hunter Medical Research Institute, Mothers and Babies Research Centre, Newcastle, New South Wales, Australia
*
*Address for correspondence: A. L. Cumberland, School of Biomedical Sciences and Pharmacy, University of Newcastle 2308, Australia. (Email [email protected])

Abstract

Placental 5α-reductase (5αR) is influenced by in utero compromises and has a role in regulating neuroactive steroid concentrations in the fetus. The objective of this study was to determine if changes in placental 5αR were associated with neonatal outcome after birth. Guinea pigs were delivered by cesarean section at term (GA69, n=22) or preterm (GA62, n=36) and the placenta collected. Preterm neonates were maintained for 24 h unless their condition deteriorated before this time. Enzyme mRNA expression of 5αR type-1 and 5αR type-2 were determined using real-time PCR. All preterm neonates had significantly higher 5αR2 expression in their placenta compared with placentae from term neonates (P<0.0001). Expression was also markedly higher in the placentae from neonates that did not survive until 24 h, compared with surviving preterm neonates (P=0.04). These findings suggest differences of in utero neurosteroidogenic capacity between surviving and non-surviving preterm guinea pig neonates. The increased 5αR2 mRNA expression in the placenta of non-survivors suggests an induction of the neurosteroid pathway due to prior exposure to an in utero compromise, with such exposure possibly a predisposing factor that contributed to their poor ex utero outcome.

Type
Brief Report
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

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References

1. Hirst, JJ, Palliser, HK, Yates, DM, Yawno, T, Walker, DW. Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies. Neurochem Int. 2008; 52, 602610.Google Scholar
2. Ghoumari, AM, Ibanez, C, El-Etr, M, et al. Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum. J Neurochem. 2003; 86, 848859.Google Scholar
3. He, J, Hoffman, SW, Stein, DG. Allopregnanolone, a progesterone metabolite, enhances behavioral recovery and decreases neuronal loss after traumatic brain injury. Restor Neurol Neurosci. 2004; 22, 1931.Google Scholar
4. Purdy, RH, Morrow, AL, Blinn, JR, Paul, SM. Synthesis, metabolism, and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes. J Med Chem. 1990; 33, 15721581.Google Scholar
5. Gilbert Evans, SE, Ross, LE, Sellers, EM, Purdy, RH, Romach, MK. 3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period. Gynecol Endocrinol. 2005; 21, 268279.CrossRefGoogle ScholarPubMed
6. Bicikova, M, Klak, J, Hill, M, et al. Two neuroactive steroids in midpregnancy as measured in maternal and fetal sera and in amniotic fluid. Steroids. 2002; 67, 399402.Google Scholar
7. Normington, K, Russell, DW. Tissue distribution and kinetic characteristics of rat steroid 5 alpha-reductase isozymes. Evidence for distinct physiological functions. J Biol Chem. 1992; 267, 1954819554.Google Scholar
8. Poletti, A, Celotti, F, Rumio, C, Rabuffetti, M, Martini, L. Identification of type 1 5α-reductase in myelin membranes of male and female rat brain. Mol Cell Endocrinol. 1997; 129, 181190.CrossRefGoogle ScholarPubMed
9. Vu, TT, Hirst, JJ, Stark, M, et al. Changes in human placental 5α-reductase isoenzyme expression with advancing gestation: effects of fetal sex and glucocorticoid exposure. Reprod Fertil Dev. 2009; 21, 599607.Google Scholar
10. Nguyen, PN, Billiards, SS, Walker, DW, Hirst, JJ. Changes in 5 alpha-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal sheep. Pediatr Res. 2003; 53, 956964.Google Scholar
11. Yawno, T, Yan, EB, Walker, DW, Hirst, JJ. Inhibition of neurosteroid synthesis increases asphyxia-induced brain injury in the late gestation fetal sheep. Neuroscience. 2007; 146, 17261733.Google Scholar
12. Kelleher, MA, Palliser, HK, Walker, DW, Hirst, JJ. Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on fetal guinea pig brain development. J Endocrinol. 2011; 208, 301309.Google Scholar
13. Gadisseux, M, Gressens, P, editors. Hypoxia Opportunism During Brain Development. Acute Perinatal Asphyxia in Term Infants: Report of the Workshop. 1997. DIANE Publishing: National Institute of Health, Bethesda, Maryland, USA.Google Scholar
14. Breeze, ACG, Lees, CC. Prediction and perinatal outcomes of fetal growth restriction. Seminars in Fetal and Neonatal Medicine. 2007; 12, 383397.Google Scholar
15. Nguyen, PN, Yan, EB, Castillo-Melendez, M, Walker, DW, Hirst, JJ. Increased allopregnanolone levels in the fetal sheep brain following umbilical cord occlusion. J Physiol. 2004; 560, 593602.Google Scholar
16. Westcott, KT, Hirst, JJ, Ciurej, I, Walker, DW, Wlodek, ME. Brain allopregnanolone in the fetal and postnatal rat in response to uteroplacental insufficiency. Neuroendocrinology. 2008; 88, 287292.Google Scholar
17. World Health Organization; March of Dimes; The Partnership for Maternal NCHStC. Born Too Soon: the Global Action Report on Preterm Birth 2012.Google Scholar
18. Saigal, S, Doyle, LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008; 371, 261269.Google Scholar
19. Garite, TJ, Clark, R, Thorp, JA. Intrauterine growth restriction increases morbidity and mortality among premature neonates. Am J Obstet Gynecol. 2004; 191, 481487.Google Scholar
20. Nguyen, PN, Billiards, SS, Walker, DW, Hirst, JJ. Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolization. Pediatr Res. 2003; 54, 840847.CrossRefGoogle ScholarPubMed
21. McKendry, AA, Palliser, HK, Yates, DM, Walker, DW, Hirst, JJ. The effect of betamethasone treatment on neuroactive steroid synthesis in a fetal guinea pig model of growth restriction. J Neuroendocrinol. 2010; 22, 166174.Google Scholar
22. Poletti, A, Negri-Cesi, P, Rabuffetti, M, et al. Transient expression of the 5α-reductase type 2 isozyme in the rat brain in late fetal and early postnatal life. Endocrinology. 1998; 139, 21712178.Google Scholar
23. Murphy, VE, Fittock, RJ, Zarzycki, PK, et al. Metabolism of synthetic steroids by the human placenta. Placenta. [Comparative Study Research Support, Non-U.S. Gov’t]. 2007; 28, 3946.Google Scholar
24. Kehoe, P, Mallinson, K, McCormick, CM, Frye, CA. Central allopregnanolone is increased in rat pups in response to repeated, short episodes of neonatal isolation. Dev Brain Res. 2000; 124, 133136.Google Scholar
25. Shapiro-Mendoza, CK, Tomashek, KM, Kotelchuck, M, et al. Risk factors for neonatal morbidity and mortality among healthy late preterm newborns. Semin Perinatol. 2006; 30, 5460.Google Scholar