In primates, including women, and in rodents, natural killer lymphocytes (NK cells) have a unique relationship with the decidualizing uterus. Implantation sites from genetically modified and transplanted mice have proven useful models for understanding potential mechanisms involved in the recruitment, activation and functions of human CD56(bright) uterine (u)NK cells. Key findings are reviewed in this article. In mice, uNK precursor cells are recruited from secondary lymphoid tissues and are activated coincident with their uterine arrival. uNK cells proliferate, produce cytokines (interferon gamma (IFN-gamma) and interleukin 18 (IL-18) and IL-27), and terminally differentiate into granulated lymphocytes. Many uNK cells proliferate within the myometrium at each implantation site forming a structure, the mesometrial lymphoid aggregate of pregnancy (MLAp) that surrounds blood vessels servicing each placenta. Post-mitotic uNK cells are abundant within decidua basalis; frequently (<25%) associating with spiral arteries, intramurally and intraluminally. From mid-gestation, numbers of uNK cells decline. Studies of implantation sites in mice lacking uNK cells, IFN-gamma, components of IFN-gamma-induction and -signalling pathways or IFN-gamma-regulated genes indicate that uNK cell-derived IFN-gamma is essential in triggering pregnancy-induced spiral artery modification. Decidual maintenance and uNK cell death are additional effects of uNK cell-derived IFN-gamma. Thus, during the first half of gestation, uNK cells contribute to and sustain important changes in the maternal placental bed.

No abstract

Background: Little is known about the prevalence and determinants of drug use among men who have sex with men (MSM) in Ireland. The aims of this study were to measure the prevalence of recreational drug use among MSM in a national sample, and to identify subgroups of MSM who may benefit from targeted preventive interventions. Methods: The MSM Internet Survey Ireland (MISI) 2015 was a community-recruited, nationally-promoted, self-completed online survey for MSM. MISI 2015 included standardised questions on recreational drugs, poppers, and drugs associated with chemsex (i.e. crystal methamphetamine, GBL/GHB, mephedrone, ketamine). Multivariable-adjusted logistic regression was used to identify factors associated with use of these substances. Results: In the previous year, 36% of MSM used recreational drugs, 33% used poppers, and 7% used drugs associated with chemsex. Five percent were diagnosed HIV-positive. Recreational drug users were significantly younger than non-users (median=27 vs. 32 years; p<0.001); popper users were significantly older than non-users (median=34 vs. 28 years; p<0.001). The odds of recreational drug use were higher among MSM diagnosed HIVpositive (vs. never tested; AOR 2.27, 95%CI 1.39-3.70). Use of poppers, and use of drugs associated with chemsex, were also higher among MSM diagnosed HIV-positive (vs. never tested; AOR 3.77, 95%CI 2.41-5.90, and AOR 5.87, 95%CI 3.08-11.18 respectively). Conclusions: The prevalence of recreational drug use is higher among MSM than in the general population in Ireland, and it is particularly high among MSM diagnosed HIV-positive. Targeted harm reduction messages and preventive interventions are warranted to complement population-based approaches to reducing drug use in this population.

Full-length cDNA for a mouse gene A2-macroglobulin induced by pregnancy (A2mp) was cloned from mesometrial decidua at Gestation Day 10. The 4622-base pair cDNA encodes a protein of 1473 AA with >70% sequence identity and all typical domains of other A2M-family members in humans and rodents, despite unique absence of hepatic expression. The bait region is most distinct and has the greatest sequence similarity with rat acute-phase A2m. Northern blotting, reverse transcription and real-time-PCR, and in situ hybridization studies using C57Bl/6 mice revealed uterine induction of A2mp during decidualization and strong, midgestational association with modifying spiral arteries. Ovaries, testes, lactating mammary glands, heart, and kidney were the only additional organs with A2mp expression that was localized to granulosa and cumulus cells in secondary follicles; primary seminiferous epithelium, including Sertoli cells, mammary alveolar, and ductal epithelium; cardiac endothelium; and renal collecting tubules, respectively. Infusion of native human A2M into pregnant alymphoid or interferon-gamma gene-ablated mice overcame blocks to pregnancy-induced spiral artery modification in these strains. Activated human A2M was also effective, suggesting mechanisms independent of proteinase inhibition. Identification of cytokines, growth factors, or other molecules bound to A2MP should provide new insights into decidualization, spiral artery modification, and cardiovascular adaptation to pregnancy.

No abstract