Models of Intrauterine growth restriction and fetal programming in rabbits

Abstract

Intrauterine growth restriction (IUGR) affects approximately 10% of human pregnancies globally and has immediate and life‐long consequences for offspring health. However, the mechanisms underlying the pathogenesis of IUGR and its association with later health and disease outcomes are poorly understood. To address these knowledge gaps, the use of experimental animals is critically important. Since the 50's different environmental, pharmacological, and surgical manipulations have been performed in the rabbit to improve our knowledge of the control of fetal growth, fetal responses to IUGR, and mechanisms by which offspring may be programmed by an adverse gestational environment. The purpose of this review is therefore to summarize the utility of the rabbit as a model for IUGR research. It first summarizes the knowledge of prenatal and postnatal development in the rabbit and how these events relate to developmental milestones in humans. It then describes the methods used to induce IUGR in rabbits and the knowledge gained about the mechanisms determining prenatal and postnatal outcomes of the offspring. Finally, it discusses the application of state of the art approaches in the rabbit, including high‐resolution ultrasound, magnetic resonance imaging, and gene targeting, to gain a deeper integrative understanding of the physiological and molecular events governing the development of IUGR. Overall, we hope to engage and inspire investigators to employ the rabbit as a model organism when studying pregnancy physiology so that we may advance our understanding of mechanisms underlying IUGR and its consequences in humans and other mammalian species.

Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

“…Trophoblast proliferation and differentiation is an intensively regulated process, and the role of several genes in placental development has been studied using various in vivo and in vitro models [16][17][18][19][20]. The pluripotency factor LIN28 is a highly conserved RNA binding protein which is expressed in placenta and has two paralogs, LIN28A and LIN28B [21,22].…”

Strategies for intra-amniotic administration of fetal therapy in a rabbit model of intrauterine growth restriction

“…5 Regarding this etiology, some methods used for IUGR induction in research are uterine artery ligation in rats, guinea pigs, rabbits, and sheep; uterine artery or placenta embolization in sheep; carunclectomy in sheep; uteroplacental vessel ligation in rats, guinea pigs, and rabbits; and progressive uterine artery occlusion in guinea pigs. [10][11][12][13] Similarly, our group has reported an IUGR induction in a rabbit model by selective surgical ligation of uteroplacental vessels in the mother in late pregnancy. 14 In this animal model, the reduced placental supply of both oxygen and nutrients resembles human placental insufficiency and results in lower birthweight and survival.…”

“…The animal model we have chosen is one that has been characterized well and used in many studies on IUGR. 11 The interventions were all fetal therapies that bypass the placenta, which is often dysfunctional in human IUGR. 38 By focusing on the actual procedures performed on animals, whose inherent characteristics are different from humans, we were able to highlight the many factors influencing the development of a new fetal therapy.…”

Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress

“…Indeed, numerous animal models of prenatal adversity have been developed in several species. Sheep, pigs, rabbits and guinea pigs are amendable to environmental manipulation and chronic instrumentation and previous reviews have highlighted their usefulness in studying developmental programming [ 18 – 21 ]. Mice and rats also offer advantages in the study of developmental programming due to the ease of maternal manipulation, availability of molecular tools (including gene manipulation) and short gestation and lifespan.…”