ContextEndometrial health is impacted by molecular processes that underlie estrogen responses.ObjectiveTo define estrogen regulation of endometrial function by integrating the estrogen receptor alpha (ESR1) cistrome and transcriptome of endometrial biopsies taken from the proliferative and midsecretory phases of the menstrual cycle and hormonally stimulated endometrial epithelial organoids.DesignESR1 ChIPseq and RNAseq were performed on proliferative or mid-secretory endometrial biopsies and on hormone treated organoid cultures.SettingEndometrial samples were obtained from volunteers at outpatient research clinics for ChIPseq and for organoid culture.Patients or Other ParticipantsParticipants were fertile, reproductive aged women with normal cycle length, and without any history of infertility or irregular cycles. In total, 5 new endometrial biopsies obtained from 5 women were used in this study and were analyzed together with previously published cycle stage endometrial RNAseq data.Intervention(s)There were no interventions in this study.Main Outcome Measure(s)The cycle stage specific ESR1 binding sites and gene expression identification of human endometrium and organoid cultures were integrated with changes in gene expression.ResultsGenes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal to the gene promoter when compared to primary endometrium. Organoid estrogen/ESR1 candidate target genes impacted formation of cellular protrusions, and chromatin modification,ConclusionsAnalysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen impacts endometrial health and function.

Endometrial health is impacted by molecular processes that underlie estrogen responses. We assessed estrogen regulation of endometrial function by integrating the estrogen receptor alpha (ESR1) cistromes and transcriptomes of endometrial biopsies taken from the proliferative and mid-secretory phases of the menstrual cycle together with hormonally stimulated endometrial epithelial organoids. The cycle stage specific ESR1 binding sites were determined by ChIPseq and then integrated with changes in gene expression from RNAseq data to infer candidate ESR1 targets in normal endometrium. Genes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal from gene promoters when compared to primary endometrium and was more similar to the proliferative than the mid-secretory phase ESR1 cistrome. Inferred organoid estrogen/ESR1 candidate target genes impacted formation of cellular protrusions, and chromatin modification. Comparison of signaling impacted by candidate ESR1 target genes in endometrium vs. organoids reveals enrichment of both overlapping and distinct responses. Our analysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen impacts endometrial health and function.

Background: Permanent sterilization is one of the most common methods of birth control in the United States and around the world. A small subset of women will regret their decision and desire future fertility. For these women, the options include in vitro fertilization (IVF) or surgical reversal. Surgical reversal, specifically via tubal reanastamosis, is an important choice to consider. Surgical reversal can be accomplished via three different general approaches including laparotomy, conventional laparoscopy, and robot-assisted approaches. Unfortunately, surgical reversal is becoming a lost art. Objective: To compare and contrast pregnancy success rates, ectopic pregnancy rates, and cost between the surgical methods and IVF. Methods: We conducted a literature review via Pubmed with keywords as listed below. Conclusion: Laparoscopic tubal reanastomosis is the best approach for women <40 years of age due to pregnancy outcomes that are comparable to other methods, cost effectiveness, and favorable safety profile of minimally invasive surgery.

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