Effects of maternal obesity on placental function and fetal development

Abstract

Obesity has reached epidemic proportions and pregnancies in obese mothers have increased risk for complications including gestational diabetes, hypertensive disorders, preterm birth and caesarian section. Children born to obese mothers are at increased risk of obesity and metabolic disease and are susceptible to develop neuropsychiatric and cognitive disorders. Changes in placental function not only play a critical role in the development of pregnancy complications but may also be involved in linking maternal obesity to long-term health risks in the infant. Maternal adipokines i.e., interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), leptin and adiponectin link maternal nutritional status and adipose tissue metabolism to placental function. Adipokines and metabolic hormones have direct impact on placental function by modulating placental nutrient transport. Nutrient delivery to the fetus is regulated by a complex interaction between insulin signaling, cytokine profile and insulin responsiveness, which is modulated by adiponectin and IL-1β. In addition, obese pregnant women are at risk for hypertension and preeclampsia with reduced placental vascularity and blood flow, which would restrict placental nutrient delivery to the developing fetus. These sometimes opposing signals regulating placental function may contribute to the diversity of short and long-term outcomes observed in pregnant obese women. This review focuses on the changes in adipokines and obesity-related metabolic hormones, how these factors influence placental function and fetal development to contribute to long-term metabolic and behavioral consequences of children born to obese mothers.

Maternal obesity accelerates rat offspring metabolic ageing in a sex‐dependent manner

“…There is now compelling evidence that J Physiol 597.23 environmental challenges, including suboptimal maternal nutrition experienced in utero and/or in early neonatal life can increase susceptibility to later life diseases such as type 2 diabetes (Portha et al 2011;Bouret et al 2015), hypertension (Ingelfinger & Nuyt, 2012;Skrypnik et al 2019) and obesity (Plagemann et al 1992;Sarr et al 2012;Zambrano & Nathanielsz, 2013). The significance of the studies presented here lies in the exponential increase in the proportion of women of reproductive years who are overweight or obese (Hanson et al 2015;Howell & Powell, 2017). We were able to show that MO prior to and throughout pregnancy and lactation programmed MOF 1 to metabolic and endocrine dysfunction and oxidative stress and predisposed MOF 1 to premature ageing and the progression of non-alcoholic fatty acid liver disease in a sex specific manner.…”

Leptin action in normal and pathological pregnancies

“…A link between bodyweight, adipokines and success of pregnancy has been proposed, although it is not fully understood . The observations that human and rodents with congenital leptin deficiencies are sterile and that anorexia and obesity modify the onset of puberty in opposite ways, led to the idea that leptin is an important player in reproduction .…”

Genomic imprinting, growth and maternal–fetal interactions

“…Low adiponectin levels during the second half of gestation are thought to increase maternal insulin resistance, thus reducing maternal glucose uptake and increasing the maternal-fetal glucose concentration gradient in favour of fetal uptake. Consistent with this, obese pregnant women and rodents who are insulin resistant give birth to large babies and have further reduced adiponectin levels (Howell and Powell, 2017). Furthermore, supplementing obese mice with adiponectin during pregnancy can reverse both maternal insulin resistance and fetal overgrowth (Aye et al, 2015).…”

“…Adiponectin is secreted from adipocytes according to their size and acts on multiple tissues, predominantly to increase insulin sensitivity (Stern et al, 2016). Adiponectin levels drop in both rodent and human pregnancy and remain low during lactation (Combs et al, 2003;Howell and Powell, 2017). Low adiponectin levels during the second half of gestation are thought to increase maternal insulin resistance, thus reducing maternal glucose uptake and increasing the maternal-fetal glucose concentration gradient in favour of fetal uptake.…”