Uterine natural killer cells (uNK) play an important role in promoting successful pregnancy by regulating trophoblast invasion and spiral artery remodelling in the first trimester. Recently, single-cell RNA sequencing (scRNAseq) on first-trimester decidua showed that uNK can be divided into three subsets, which may have different roles in pregnancy. Here we present an integration of previously published scRNAseq datasets, together with novel flow cytometry data to interrogate the frequency, phenotype, and function of uNK1–3 in seven stages of the reproductive cycle (menstrual, proliferative, secretory phases of the menstrual cycle; first, second, and third trimester; and postpartum). We found that uNK1 and uNK2 peak in the first trimester, but by the third trimester, the majority of uNK are uNK3. All three subsets are most able to degranulate and produce cytokines during the secretory phase of the menstrual cycle and express KIR2D molecules, which allow them to interact with HLA-C expressed by placental extravillous trophoblast cells, at the highest frequency during the first trimester. Taken together, our findings suggest that uNK are particularly active and able to interact with placental cells at the time of implantation and that uNK1 and uNK2 may be particularly involved in these processes. Our findings are the first to establish how uNK frequency and function change dynamically across the healthy reproductive cycle. This serves as a platform from which the relationship between uNK function and impaired implantation and placentation can be investigated. This will have important implications for the study of subfertility, recurrent miscarriage, pre-eclampsia, and pre-term labour.

Rates of stenosis after prostate cancer treatment appear similar across all primary treatment modalities including radical prostatectomy, radiation therapy, cryoablation, and high-intensity focused ultrasound in contemporary series. Urethral dilation and urethrotomy continue to report moderate patency rates. Urethroplasty achieves high patency rates even for long strictures, but more extensive reconstruction increases the risk of postoperative urinary incontinence. Recent AUA guidelines on urethral strictures provide new recommendations for management of these patients. All treatment options for prostate cancer carry a risk for bladder outlet obstruction, and intervention is often necessary to relieve long-lasting morbidity. Careful preoperative evaluation should be completed to assess location and extent of the stricture in order to choose optimal therapy. Endoscopic treatments, open reconstruction, and urinary diversion all play a role in relief of stenosis depending on stricture length, location, characteristics, and patient comorbidities.

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