Placentome- and sex-specific differences in glucocorticoids and their receptor variants in the growth restricted sheep
Date
2023
Authors
Meakin, A.
Clifton, V.
Darby, J.
Holman, S.
Wiese, M.
Morrison, J.
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Advisors
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Conference paper
Citation
Placenta, 2023, vol.140, pp.E47-E47
Statement of Responsibility
Conference Name
Annual Meeting of the International-Federation-of-Placenta-Associations (IFPA) (5 Sep 2023 - 8 Sep 2023 : Rotorua, New Zealand)
Abstract
Objectives: Despite their importance in adapting to intrauterine homeostatic shifts to maintain normal feto-placental physiology, chronic exposure to elevated glucocorticoid concentrations can disrupt placental, and thus fetal, growth. Indeed, fetal growth restriction (FGR) increases placental exposure to glucocorticoids in sheep, which influences phenotypically distinct placentome distribution. However, the impact this has on placentome-specific glucocorticoid receptor (GR) signalling pathways is unclear. In human and rodent studies of FGR, males initiate a state of glucocorticoid resistance by upregulating low-transactivational GR protein isoforms in an attempt to maintain growth at the cost of placental reserve capacity. This exacerbates their risk for intrauterine morbidity and mortality, but whether this adaptation is conferred across multiple species is unclear. Therefore, in the current study, we have examined the impact FGR has on placentome-specific glucocorticoid signalling in sheep.
Methods: Non-pregnant Merino ewes underwent carunclectomy surgery to induce FGR. Placentome type B and D from control (female n=9; male n=11) and FGR (female n=9; male n=6) placentae (140d gestation) were used for cortisol concentration quantitation using liquid chromatography-tandem mass spectrometry and subcellular GR protein expression using Western blot.
Results: In females, placental cortisol concentration was increased in FGR (P=0.00183), whereas no change between study groups was observed in males. In both sexes, cortisol concentrations were reduced in placentome Ds when compared with placentome Bs irrespective of study group. There were no female-specific changes to GR isoform expression in response to FGR. In males, nuclear GR-A was increased in response to FGR (P=0.0380) and was reduced in placentome Ds when compared with placentome Bs (P=0.0065).
Conclusion: Altered placentome-specific cortisol concentrations may contribute to proposed functional differences between placentome types. In addition, increased nuclear expression of the low transactivational isoform GR-A in the FGR male may confer a state of glucocorticoid resistance that consequently increases intrauterine morbidity and mortality risks.
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Copyright 2023 Elsevier Ltd.