Phenotype of early-onset fetal growth restriction in sheep

Amy E Sutherland; Tegan A White; Charmaine R Rock; Beth R Piscopo; Ingrid Dudink; Ishmael M Inocencio; Zahrah Azman; Yen Pham; Ilias Nitsos; Atul Malhotra; Tamara Yawno; Graeme R Polglase; Graham Jenkin; Emily J Camm; Beth J Allison; Suzanne L Miller

doi:10.3389/fendo.2024.1374897

Phenotype of early-onset fetal growth restriction in sheep

Front Endocrinol (Lausanne). 2024 Mar 13:15:1374897. doi: 10.3389/fendo.2024.1374897. eCollection 2024.

Authors

Amy E Sutherland^{1

2}, Tegan A White^{1

2}, Charmaine R Rock^{1

2}, Beth R Piscopo^{1

2}, Ingrid Dudink^{1

2}, Ishmael M Inocencio^{1

2}, Zahrah Azman^{1

2}, Yen Pham^{1

2}, Ilias Nitsos^{1

2}, Atul Malhotra^{1

3

4}, Tamara Yawno^{1

2

3}, Graeme R Polglase^{1

2}, Graham Jenkin^{1

2}, Emily J Camm^{1

2}, Beth J Allison^{1

2}, Suzanne L Miller^{1

2}

Affiliations

¹ The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, Australia.
² Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, Australia.
³ Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
⁴ Monash Newborn, Monash Children's Hospital, Melbourne, VIC, Australia.

Abstract

Introduction: Fetal growth restriction (FGR) is a common pregnancy complication, caused by placental insufficiency, with serious adverse consequences for development in utero and postnatal wellbeing. There are no antenatal treatments to improve growth or organ development in FGR, and animal models are essential to mimic the physiological adaptations in FGR and to assess potential interventions. This study aimed to identify the temporal nature of reduced developmental trajectory in fetuses with FGR, and to examine the effects of common factors that may mediate differential growth such as glucocorticoid treatment. We hypothesised that the trajectory of growth would be adversely impacted by FGR.

Methods: FGR was induced via surgical placental insufficiency in fetal sheep (89 days gestation/0.6 gestation; n=135) and compared to age-matched controls over the last third of gestation and into neonatal life (n=153).

Results: Body weight of FGR fetuses/lambs was significantly reduced compared to controls (p<0.0001) from 127 days of gestation (term is 148 days), with increased brain:body weight ratio (p<0.0001) indicative of brain sparing. All biometric measures of body size were reduced in the FGR group with the exception of biparietal (head) diameter. The trajectory of body growth in the last trimester of sheep pregnancy was significantly reduced in the FGR group compared to controls, and stillbirth rate increased with longer gestation.

Discussion: This work provides a well characterised FGR animal model that mimics the known physiological adaptations in human pregnancy and can be used to determine the efficacy of potential interventions.

Keywords: FGR; IUGR; asymmetric growth; brain injury; brain sparing; neurodevelopment; postnatal; preterm.

MeSH terms

Animals
Body Weight
Female
Fetal Growth Retardation* / etiology
Humans
Phenotype
Placenta
Placental Insufficiency*
Pregnancy
Sheep

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the National Health and Medical Research Council: (#173731, #2016688, #1175843), the Cerebral Palsy Alliance of Australia, and the Victorian Government’s Operational Infrastructure Support Program. Monash University supported student scholarships to members of this project.