The pathophysiology of the septate uterus: a systematic review.

BACKGROUND: Little is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus. OBJECTIVES: We explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects. SEARCH STRATEGY: We performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018. SELECTION CRITERIA: We selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated potentially eligible papers. MAIN RESULTS: Thirty-eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall. CONCLUSIONS: We found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum. TWEETABLE ABSTRACT: In women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.

ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function.

The molecular mechanisms that promote excitatory synapse development have been extensively studied. However, the molecular events preventing precocious excitatory synapse development so that synapses form at the correct time and place are less well understood. Here, we report the functional characterization of ARHGAP12, a previously uncharacterized Rho GTPase-activating protein (RhoGAP) in the brain. ARHGAP12 is specifically expressed in the CA1 region of the hippocampus, where it localizes to the postsynaptic compartment of excitatory synapses. ARHGAP12 negatively controls spine size via its RhoGAP activity and promotes, by interacting with CIP4, postsynaptic AMPA receptor endocytosis. Arhgap12 knockdown results in precocious maturation of excitatory synapses, as indicated by a reduction in the proportion of silent synapses. Collectively, our data show that ARHGAP12 is a synaptic RhoGAP that regulates excitatory synaptic structure and function during development.