Uterine contractions depend on KIT-positive interstitial cells in the mouse: genetic and pharmacological evidence

In the gastrointestinal tract, interstitial cells of Cajal (ICCs) generate a pacemaker activity. They produce electric slow waves that trigger and coordinate gut smooth muscle contractions. Interstitial cells of Cajal's slender shape is revealed by KIT immunostaining. Based on several features, including KIT expression and KIT dependence, ICC-like cells were identified in nongastrointestinal tissues. Here, we investigated in the mouse whether uterine contractions depend on ICC-like cells' activity. By labeling KIT-expressing cells, we found putative ICC-like cells in the uterus, observed as KIT-positive interstitial, long spindle-shaped cells with fine branched cytoplasm processes, distributed in muscular layers and in subepithelial connective tissue. We then checked the potential KIT dependence of ex vivo contractile activity of the uterus by combining genetic and pharmacological approaches, using the Kit W-v hypomorphic mutation, and imatinib as a KIT noncompetitive inhibitor. We found a significant reduction in frequency of longitudinal uterine contractions in Kit W-v/Kit W-v compared with Kit+/+ mice, whereas amplitude was unaffected. There was no difference in frequency or amplitude of circular uterine contractions between Kit W-v/Kit W-v and Kit+/+ mice. Ex vivo treatment of Kit+/+ uterine horns with imatinib resulted in a dose-dependent reduction of the frequency and amplitude of longitudinal myometrial contractions. Amplitude and frequency of circular contractions were unaffected in presence of imatinib. These concurrent results suggest that longitudinal contractions of the uterus depend on a KIT signaling pathway of ICC-like cells. The existence of ICC-like cells in the myometrium may enhance our understanding of uterine spontaneous contractile activity and suggest new approaches for treatment of uterine contractility disorders.     

Body protein does not vary despite seasonal changes in fat in the White Stork Ciconia ciconia

To understand how a large soaring bird, the White Stork Ciconia ciconia , copes with energy constraints, we compared changes in body mass in 14 captive adult storks with the body composition of 12 free-ranging adult storks found dead from accidents. The captive storks, already in an enclosure for several years, were fed ad libitum . They were weighed daily for 1.53.5 years using an automatic device. The bodies of the accidentally killed storks were analysed to determine total water, lipid, protein and ash contents, and to assess the biochemical composition of certain organs. Females were on average 20% lighter and 24% smaller than males, but the body mass of the sexes varied in parallel throughout the year. Body mass peaked in December and January (2530% above minimal body mass), due essentially to large fat stores in subcutaneous and abdominal adipose tissues. Body mass and body lipid rapidly decreased from February to June, whether the storks reared chicks successfully or not, and remained minimal for a few days into July. In contrast to birds using flapping flight, no variation in body protein or pectoral muscle protein was observed while breeding, even though the moult occurred then, nor in August, before the time when wild storks migrate. An endogenous regulation of body fuels is discussed.     

Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo.

The mouse develops five pairs of mammary glands that arise during mid-gestation from five pairs of placodes of ectodermal origin. We have investigated the molecular mechanisms of mammary placode development using Lef1 as a marker for the epithelial component of the placode, and mice deficient for Fgf10 or Fgfr2b, both of which fail to develop normal mammary glands. Mammary placode induction involves two different signaling pathways, a FGF10/FGFR2b-dependent pathway for placodes 1, 2, 3 and 5 and a FGF10/FGFR2b-independent pathway for placode 4. Our results also suggest that FGF signaling is involved in the maintenance of mammary bud 4, and that Fgf10 deficient epithelium can undergo branching morphogenesis into the mammary fat pad precursor.     

Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo-obstruction syndrome

Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo-obstruction (CIPO) syndrome, a life-threatening intestinal motility disorder. We showed that CIPO-SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet-Derived Growth Factor Receptor-alpha (PDGFRA) expression. We showed that this modulation occurs without origin-related differences in CIPO circular and longitudinal-derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO-SMC towards an undifferentiated stage. The development of CIPO-SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO.     

Tarsal taste sensilla of the autumn gum moth, Mnesampela privata: morphology and electrophysiological activity

Mnesampela privata Guenée (Lepidoptera: Geometridae: Ennominae) is a native Australian geometrid that conducts considerable host assessment prior to ovipositing on its host plants, which belong to the genus Eucalyptus . The leaves of some of their hosts are covered with a particularly thick and waxy cuticle and we have shown that epicuticular waxes influence the oviposition preferences of females. This necessitates that M. privata has evolved specific chemosensory organs to assess the identity and perhaps even the quality of its hosts. In this work, we examined the morphology of tarsal taste sensilla and the sensitivity of their sensory neurones to a range of primary metabolites possibly influential on host assessment and oviposition. The ventral surface of the fifth tarsomere of females bear two parallel rows of up to eight sensilla, each loosely aligned with two parallel rows of five spines. Salts, sugars, and amino acids elicited phasi-tonic multicellular neuronal responses of variable magnitude and form. Two pairs of sensilla are closely apposed to the most distal spine in each row; the sensory neurones associated with these sensilla exhibited notably larger responses to alanine and serine compared with those of all other sensilla. The arrangement of the taste sensilla in close proximity to prominent tarsal spines is unique and could represent an adaptation that enables them to penetrate the wax layer and be brought into contact with primary metabolites present closer to the leaf surface.     

Sexual Dimorphism of the Feto-Placental Phenotype in Response to a High Fat and Control Maternal Diets in a Rabbit Model

Maternal environment during early developmental stages plays a seminal role in the establishment of adult phenotype. Using a rabbit model, we previously showed that feeding dams with a diet supplemented with 8% fat and 0.2% cholesterol (HH diet) from the prepubertal period and throughout gestation induced metabolic syndrome in adult offspring. Here, we examined the effects of the HH diet on feto-placental phenotype at 28 days post-coïtum (term = 31days) in relation to earlier effects in the blastocyst (Day 6). At 28 days, both male and female HH fetuses were intrauterine growth retarded and dyslipidemic, with males more affected than females. Lipid droplets accumulated in the HH placentas’ trophoblast, consistent with the increased concentrations in cholesteryl esters (3.2-fold), triacylglycerol (2.5-fold) and stored FA (2.12-fold). Stored FA concentrations were significantly higher in female compared to male HH placentas (2.18-fold, p<0.01), whereas triacylglycerol was increased only in HH males. Trophoblastic lipid droplet accumulation was also observed at the blastocyst stage. The expression of numerous genes involved in lipid pathways differed significantly according to diet both in term placenta and at the blastocyst stage. Among them, the expression of LXR-α in HH placentas was reduced in HH males but not females. These data demonstrate that maternal HH diet affects the blastocyst and induces sex-dependent metabolic adaptations in the placenta, which appears to protect female fetuses from developing severe dyslipidemia.