Deregulation of the endometrial stromal cell secretome precedes embryo implantation failure

STUDY QUESTION Is implantation failure following ART associated with a perturbed decidual response in endometrial stromal cells (EnSCs)? SUMMARY ANSWER Dynamic changes in the secretome of decidualizing EnSCs underpin the transition of a hostile to a supportive endometrial microenvironment for embryo implantation; perturbation in this transitional pathway prior to ART is associated with implantation failure. WHAT IS KNOWN ALREADY Implantation is the rate-limiting step in ART, although the contribution of an aberrant endometrial microenvironment in IVF failure remains ill defined. STUDY DESIGN, SIZE, DURATION In vitro characterization of the temporal changes in the decidual response of primary EnSCs isolated prior to a successful or failed ART cycle. An analysis of embryo responses to secreted cues from undifferentiated and decidualizing EnSCs was performed. The primary clinical outcome of the study was a positive urinary pregnancy test 14 days after embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary EnSCs were isolated from endometrial biopsies obtained prior to IVF treatment and cryopreserved. EnSCs from 10 pregnant and 10 non-pregnant patients were then thawed, expanded in culture, subjected to clonogenic assays, and decidualized for either 2 or 8 days. Transcript levels of decidual marker gene [prolactin (PRL), insulin-like growth factor binding protein 1 (IGFBP1) and 11β-hydroxysteroid dehydrogenase (HSD11B1)] were analysed using real-time quantitative PCR and temporal secretome changes of 45 cytokines, chemokines and growth factors were measured by multiplex suspension bead immunoassay. The impact of the EnSC secretome on human blastocyst development was scored morphologically; and embryo secretions in response to EnSC cues analyzed by multiplex suspension bead immunoassay. MAIN RESULTS AND THE ROLE OF CHANCE Clonogenicity and induction of decidual marker genes were comparable between EnSC cultures from pregnant and non-pregnant group groups (P > 0.05). Analysis of 23 secreted factors revealed that successful implantation was associated with co-ordinated secretome changes in decidualizing EnSCs, which were most pronounced on Day 2 of differentiation: 17 differentially secreted proteins on Day 2 of decidualization relative to undifferentiated (Day 0) EnSCs (P 0.05)

On the Asymptotic Structure of the Stabilizing Solution of the Riccati Equation Arising in Connection with the Linear Quadratic Regulator Problem for a System Described by Itȏ Differential Equations with Two Fast Time Scales

Only AbstractWe consider a stochastic optimal control problem described by a quadratic performance criterion and a linear controlled system modeled by a system of singularly perturbed Itȏ differential equations with two fast time scales. Our goal is to analyse the asymptotic structure with respect to the small parameters εj > 0, j = 1, 2 associated to the two fast time scales of the stabilizing solution of the matrix Riccati equation associated to the optimal control problem under consideration. The results derived in this stochastic framework cannot be obtained mutatis-mutandis from the already existing ones in the deterministic case, as those from

Output peak control of nonhomogeneous markov jump system with unit-energy disturbance

This paper considers output peak controller design for discrete nonhomogeneous Markov jump systems under unit-energy disturbance. The mode-dependent output peak feedback controller is designed to ensure that the resulting closed-loop system is stochastically stable and the peak of the output is within a specified range. Furthermore, the optimal energy-to-peak gain indices of the mode-dependent and the mode-independent state feedback controllers are evaluated and compared. A numerical example is presented to illustrate the applicability of the results obtained

Stochastic stabilization of a class of nonhomogeneous Markovian jump linear systems

International audienceThis paper deals with the problem of stochastic stability analysis and control synthesis of a class of Markovian jump linear systems (MJLS) with time-varying transition probabilities (TPs) in the discrete-time domain. The time-varying character is considered to be in a polytopic sense. The approach followed in this note is based on the use of a parameter dependent stochastic Lyapunov function. We give a stability condition in terms of a linear matrix inequalities (LMI) feasibility problem. The obtained results are illustrated in a numerical example