Rodent models in placental research. Implications for fetal origins of adult disease

Abstract

Rodent models in rats, mice, and guinea pigs have been extremely helpful to gain insight into pregnancy physiology and pathologies-related. Moreover, they have allowed understanding the mechanism that links an adverse intrauterine environment with the origin of adult disease. In this regard, the effects of diverse maternal conditions, such as undernutrition, obesity, hypoxia, and hyperandrogenism on placental function and its long-term consequences for the offspring, have been widely analyzed through rodents models involving dietary manipulations, modifications in environmental oxygen, surgical and pharmacological procedures that reduce uteroplacental blood flow and administrations of exogenous testosterone and dihydrotestosterone (DHT) mimicking maternal androgen excess. Both in human and in rodent models, these interventions induce modifications of placental morphology, transport of glucose, amino acid, and fatty acids, steroid synthesis, and signaling pathways control placental function. These changes are associated with the increase of pro-inflammatory and oxidative stress markers. For its part, offspring exhibit alterations in organs involved in metabolic control such as the hypothalamus, adipose tissue, liver, skeletal muscle, and pancreas altering the intake and preferences for certain foods, the metabolism of glucose and lipid, and hormonal function leading to fat accumulation, insulin resistance, fatty liver, dyslipidemia, and elevated glucose levels. Therefore, the present review discusses the evidence emerging from rodent models that relate maternal nutrition, hypoxia, and androgen exposure to the maternal mechanisms that lead to fetal programming and their metabolic consequences in postnatal life.

Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP)

“…This can be explained by the fact that rat gestation is shorter than human pregnancy, with pups at birth more immature than human neonates. 68 Thus, a 5-day treatment with PT2385 appears to be too short to significantly improve fetal weight.…”

Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy

“…This sequelae of events in rodents leads to the formation of a transient extraembryonic organ that shares many functional characteristics with human placenta, despite species-specific differences exist, making it a valid biological model to identify the molecular mechanisms underlying the intricate crosstalk between mother and fetus both under physiological and pathological conditions [ 44 ].…”

Mechanism of leptin-NPY on the onset of puberty in male offspring rats after androgen intervention during pregnancy

“…With the development of 'Fetal Origin of Adult Disease' (FOAD) and 'Development Origin of Health and Disease' (DOHaD) (11,12), an increasing number of studies have linked the endocrine environment during pregnancy to the long-term effects on future generations (13)(14)(15)(16). With lifestyle changes and the effects of exogenous endocrine disruptors (17), the proportion of women with high androgen levels during pregnancy was significantly increased (18)(19)(20).…”