Our results demonstrate the existence of an endometrial microbiota that is highly stable during the acquisition of endometrial receptivity. However, pathological modification of its profile is associated with poor reproductive outcomes for in vitro fertilization patients. This finding adds a novel microbiological dimension to the reproductive process.

The monthly remodeling, shedding, and regeneration of the endometrium defining the human menstrual cycle is driven by gene expression changes in the underlying tissue hierarchy. Significant heterogeneity exists among cell types in the endometrium, such that multiple cell types vary dramatically in state through a monthly cycle and undergo various forms of differentiation at rapid rates. Histologic analysis and whole-tissue transcriptomic profiling have defined a specific molecular state as the optimal timing of the window of implantation (WOI) for in vitro fertilization transfer.This single-cell transcriptomic analysis aimed to characterize the transcriptomic transformation of human endometrium at single-cell resolution across the menstrual cycle, including at the WOI. Endometrial biopsies were collected from 19 healthy ovum donors between 4 and 27 days following menses, and single cells were captured and complementary DNA was generated using Fluidigm C1 medium chips. Six cell types were identified across the menstrual cycle: stromal fibroblast, endothelium, macrophage, lymphocyte, ciliated epithelium, and unciliated epithelium.Endometrial transformation was analyzed by within-cell type t-SNE using whole-transcriptome data from unciliated epithelia and stromal fibroblasts, the 2 major contributing cell types to endometrial transformation. This revealed 4 major, time-associated phases of both cell types. Among unciliated epithelia, single-cell gene dynamics were relatively continuous across phases 1 to 3 until an abrupt activation of genes consistently reported in whole-tissue transcriptomic data sets as overexpressed in the WOI marked entrance into phase 4. Among stromal fibroblasts, the WOI was characterized by widespread decidualization that became gradually upregulated through phase progression. Likewise, the WOI closed with more gradual transition dynamics in both cell types.The traditional definition of endometrial phases, consisting of the proliferative and secretory phases, correlated with the 4 phases identified here through single-cell analysis. Cell-cycling was elevated in phases 1 and 2 and ceased in later phases, suggesting the transition from proliferative to secretory occurred between phase 2 and 3. At the transcriptomic level, proliferative endometrium can be divided into 2 distinct phases with unique transcriptomic signatures.This study involved the systematic characterization of the human endometrium across the menstrual cycle through dynamic gene expression mapping. The results demonstrate that ciliated epithelium are a transcriptomically distinct endometrial cell type that are highly prevalent in the human endometrium and constantly changing in abundance across the cycle. This study likewise demonstrated an abrupt and strong transcriptomic activation in unciliated epithelia and a gradual activation in stromal fibroblasts to define the opening of the WOI, indicating a potential diagnostic target for more precise in vitro fertilization and embryo transfer.

The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology.

(Abstracted from Am J Obstet Gynecol 2016;215(6):684–703) In 2002, the vaginal microbiota was first identified using molecular methods that allowed detection of nonculturable bacteria. Alterations in vaginal microbiota could have clinical implications for reproductive and obstetric processes.

In Arabidopsis thaliana, DES1 is the only identified L-Cysteine desulfhydrase located in the cytosol, and it is involved in the degradation of cysteine and the concomitant production of H 2 S in this cell compartment. Detailed characterization of the T-DNA insertion mutants des1-1 and des1-2 has provided insight into the role of sulfide metabolically generated in the cytosol as a signaling molecule. Mutations of L-CYS DESULFHYDRASE 1 (DES1) impede H 2 S generation in the Arabidopsis cytosol and strongly affect plant metabolism. Senescence-associated vacuoles are detected in mesophyll protoplasts of des1 mutants. Additionally, DES1 deficiency promotes the accumulation and lipidation of the ATG8 protein, which is associated with the process of autophagy. The transcriptional profile of the des1-1 mutant corresponds to its premature senescence and autophagy-induction phenotypes, and restoring H 2 S generation has been shown to eliminate the phenotypic defects of des1 mutants. Moreover, sulfide is able to reverse ATG8 accumulation and lipidation, even in wild-type plants when autophagy is induced by carbon starvation, suggesting a general effect of sulfide on autophagy regulation that is unrelated to sulfur or nitrogen limitation stress. Our results suggest that cysteine-generated sulfide in the cytosol negatively regulates autophagy and modulates the transcriptional profile of Arabidopsis.

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Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.

H.O.D.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc, and Myovant Sciences GmbH. H.O.D.C. receives royalties from UpToDate for article on abnormal uterine bleeding. A.K. receives royalties from UpToDate, Wolters Kluwer for work on the topic hysterosalpingography. E.E.M. consults for Myovant Sciences. K.A.M. is coinvestigator for Bayer Essure longitudinal research study and clinical trial (all funds for this research go to the site of research [W.I.H.] e no personal compensation). K.A.M. is scientific advisor for Myovant (advises on patient questionnaires related to AUB-compensation goes to employer [C.N.E.M.G.]-no personal compensation). K.A.M. has received honoraria from ABOG, ACOG, and NIH for participating in working groups and meetings. K.A.M. is HHS Office of Population Affairs Title X Grant Reviewer (received honorarium). I.M. is employee of Igenomix R&D. C.S. is Head of the Igenomix Scientific Advisory Board. The other authors report no conflict of interest.