Leptin Is Not Necessary for Gestation and Parturition But Regulates Maternal Nutrition via a Leptin Resistance State

Abstract

Leptin levels are significantly elevated in pregnant mice, rats and humans suggesting a critical role for leptin during gestation. To address whether leptin plays a putative role in the physiology of pregnancy, we asked whether a mouse pregnancy would be affected by the complete absence of leptin from both the mother and fetuses. Thus, leptin-deficient ob/ob females were first treated with exogenous leptin and then mated to similarly treated ob/ob males. All resulting fetuses have an ob/ob genotype and lack like their mothers any endogenous leptin production. Withdrawal of leptin treatment at 0.5, 6.5, 10.5 and 19.5 days p.c. did not affect any stage of the pregnancy despite a gradual return of the mothers to an obese state. However, some mice had delayed gestation periods of 21-23 days which were associated with prolonged parturition. The pups were normally delivered with no obvious signs of deformities although none survived beyond a day after delivery due to failure of lactation. Monitoring daily food intake of pregnant ob/ob females treated throughout gestation with leptin revealed significantly elevated levels of food intake from day 10 p.c. and onward demonstrating an attenuation of a leptin response during pregnancy and a leptin resistance effect. These studies demonstrate that in the mouse, leptin is not a critical molecule for implantation, gestation, fetal growth and parturition but that the leptin resistance effect at mid-gestation aims to stimulate food intake thus providing sustained energy resources for pregnancy.

Cellular signatures in the primary visual cortex of phylogeny and placentation

“…Data on reproductive traits were taken from the literature. Species were tested both as taxonomic groups-primates, carnivores, and eutherians (Table 1)-and according to mode of placentation-epitheliochorial, endotheliochorial, and haemochorial (Table 2)-defined here as the degree of invasion of trophoblast cells into the uterus (Mossman 1987). The eutherian taxonomic group consists of 32 species (spanning 13 phylogenetic orders), and includes: 14 species that are neither primates nor carnivores and a representative sampling of primate and carnivore species that was limited to three species in any taxonomic family.…”

“…Our data support this prediction. The SMA scaling exponent for glial cell density on neuronal density in the epitheliochorial group, in which the fetus has only indirect access to the maternal blood supply (Mossman 1987), is hypometric for species mean data and negative for independent contrasts, whereas the slopes for independent contrasts in the endotheliochorial and haemochorial species (Fig. 5), in which the fetus has more direct access to the maternal blood supply than species in the epitheliochorial group, scale with positive allometry.…”

“…One link between placentation and fetal brain development that may be of evolutionary significance is leptin, a protein hormone produced by adipose tissue and placenta. Leptin has been shown to be important for the regulation of maternal energy balance (Zhang et al 1994;Pelleymounter et al 1995;Mounzih et al 1998;Trayhurn et al 1998), but also for normal neuronal and glial maturation in the developing fetal brain (Ahima et al 1999). As placental leptin expression and secretion are species-specific traits that may have been adapted for different levels of adiposity during gestation in different species (Zhao al.…”

“…The aim of the study was to examine phylogenetic diversity in the quantitative histological organization of a homologous cortical area and test for relationships with evolutionary increases in metabolic activity, phylogenetic divergences, specializations in behavior, and developmental constraints. Furthermore, as recent evidence has shown that three placental types exist across the eutherian phylogeny (Lewitus and Soligo 2011), and that these types may be approximated by the degree of invasion of trophoblast cells into the uterus (Mossman 1987), we analyzed our data according to placental invasiveness to determine whether elements of placentation may influence variation in the mammalian cortex.…”

Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males

“…In this context, very high concentrations of progesterone and estrogens promote the switch of the immune response towards the Th2 phenotype [1], and high placental production of leptin causes peripheral leptin receptor (ObRb) desensitization [30], inhibiting the Th1 cell-mediated immune response. Conversely, systemic lupus erythematosus (SLE), mainly sustained by Th2 cytokines, is worsened during pregnancy possibly due to Th2 environment present in this condition [1,31].…”