The Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage

In each menstrual cycle, the endometrium becomes receptive to embryo implantation while preparing for tissue breakdown and repair. Both pregnancy and menstruation are dependent on spontaneous decidualization of endometrial stromal cells, a progesterone-dependent process that follows rapid, oestrogen-dependent proliferation. During the implantation window, stromal cells mount an acute stress response, which leads to the emergence of functionally distinct decidual subsets, reflecting the level of replication stress incurred during the preceding proliferative phase. Progesterone-dependent, anti-inflammatory decidual cells (DeC) form a robust matrix that accommodates the conceptus whereas pro-inflammatory, progesterone-resistant stressed and senescent decidual cells (senDeC) control tissue remodelling and breakdown. To execute these functions, each decidual subset engages innate immune cells: DeC partner with uterine natural killer (uNK) cells to eliminate senDeC, while senDeC co-opt neutrophils and macrophages to assist with tissue breakdown and repair. Thus, successful transformation of cycling endometrium into the decidua of pregnancy not only requires continuous progesterone signalling but dominance of DeC over senDeC, aided by recruitment and differentiation of circulating NK cells and bone marrow-derived decidual progenitors. We discuss how the frequency of cycles resulting in imbalanced decidual subpopulations may determine the recurrence risk of miscarriage and highlight emerging therapeutic strategies.

The markers of stress in swine oral fluid

Introduction The study measured the hormonal and protein markers of acute stress, those of oxidative stress and total antioxidant capacity (TAC) in swine oral fluid, determined which of these parameters would be the most appropriate for future livestock welfare assessment and established the time when the samples should be taken. Material and Methods Stress was induced in 7 out of 14 castrated six-week-old Danbred×Duroc pigs by immobilisation on a nasal snare at 8 a.m., 1 p.m., and 6 p.m. and samples were taken both directly after the stressor was applied and 30 min later. The remaining pigs were the control group, which were not immobilised; their samples were taken at the same times. The concentrations of hormones and malondialdehyde (MDA) were measured using liquid chromatography with tandem mass spectrometry, while those of alpha-amylase and TAC were measured using spectrophotometry. Results The levels of cortisol and cortisone increased with statistical significance immediately after the acute stress response and 30 min later. A cut-off value set at 0.25 ng/mL cortisol concentration was capable of distinguishing between the stressed and control groups with 100% accuracy in evening samples and 95% accuracy overall. Prednisolone was not present, and the levels of testosterone and corticosterone were low and not distinctive. Alpha-amylase became significantly more concentrated during stress induction and 30 min later. The TAC and MDA levels rose after the stress but without statistical significance. Conclusion The most suitable markers of acute stress were cortisol, cortisone and alpha-amylase. Oral fluid is a reliable material for monitoring the level of pigs’ stress and should be collected in the evening.

Post Orgasmic Illness Syndrome (POIS) and Delayed Onset Muscle Soreness (DOMS): Do They Have Anything in Common?

Post orgasmic illness syndrome is a rare, mysterious condition with an unknown pathomechanism and uncertain treatment. The symptoms of post orgasmic illness syndrome last about 2–7 days after an ejaculation. The current hypothesis proposes that the primary injury in post orgasmic illness syndrome is an acute compression proprioceptive axonopathy in the muscle spindle, as is suspected in delayed onset muscle soreness. The terminal arbor degeneration-like lesion of delayed onset muscle soreness is theorized to be an acute stress response energy-depleted dysfunctional mitochondria-induced impairment of Piezo2 channels and glutamate vesicular release. The recurring symptoms of post orgasmic illness syndrome after each ejaculation are suggested to be analogous to the repeated bout effect of delayed onset muscle soreness. However, there are differences in the pathomechanism, mostly attributed to the extent of secondary tissue damage and to the extent of spermidine depletion. The spermidine depletion-induced differences are as follows: modulation of the acute stress response, flu-like symptoms, opioid-like withdrawal and enhanced deregulation of the autonomic nervous system. The longitudinal dimension of delayed onset muscle soreness, in the form of post orgasmic illness syndrome and the repeated bout effect, have cognitive and memory consequences, since the primary injury is learning and memory-related.

Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats

While many people experience potentially threatening events during their life, only a minority develops posttraumatic stress disorder (PTSD). The identification of individuals at risk among those exposed to trauma is crucial for PTSD prevention in the future. Since re-experiencing trauma elements outside of the original trauma-context is a core feature of PTSD, we investigate if the ability to bind memories to their original encoding context (i.e. memory contextualisation) predicts PTSD vulnerability. We hypothesize that pre-trauma neutral memory contextualization (under stress) negatively relates to PTSD-like behavior, in a prospective design using the cut-off behavioral criteria rat model for PTSD. 72 male Sprague Dawley rats were divided in two experimental groups to assess the predictive value of 1) memory contextualization without acute stress (NS-group) and 2) memory contextualization during the recovery phase of the acute stress-response (S-group) for susceptibility to PTSD-like behavior. A powerful extension to regression analysis -path analysis- was used to test this specific hypothesis, together with secondary research questions. Following traumatic predator scent stress, 19.4% of the rats displayed PTSD-like behavior. Results showed a negative relation between pre-trauma memory contextualization and PTSD-like behavior, but only in the NS-group. Pre-trauma memory contextualization was positively related to fear association in the trauma environment, again only in the NS group. If the predictive value of pre-trauma contextualization of neutral information under non-stressful conditions for PTSD susceptibility is replicated in prospective studies in humans, this factor would supplement already known vulnerability factors for PTSD and improve the identification of individuals at risk among the trauma exposed, especially those at high trauma risk such as soldiers deployed on a mission.

Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment?

The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.

Chronic adolescent stress increases exploratory behavior but does not change the acute stress response in adult male C57BL/6 mice

Chronic stress exposure in adolescence can lead to a lasting change in stress responsiveness later in life and is associated with increased mental health issues in adulthood. Here we investigate whether the Chronic Social Instability (CSI) paradigm in mice influences the behavioural and molecular responses to novel acute stressors, and whether it alters physiological responses influenced by the noradrenergic system. Using large cohorts of mice, we show that CSI mice display a persistent increase in exploratory behaviors in the open field test alongside small but widespread transcriptional changes in the ventral hippocampus. However, both the transcriptomic and behavioural responses to novel acute stressors are indistinguishable between groups. In addition, the pupillometric response to a tail shock, known to be mediated by the noradrenergic system, remains unaltered in CSI mice. Ultra-high performance liquid chromatography analysis of monoaminergic neurotransmitter levels in the ventral hippocampus also shows no differences between control or CSI mice at baseline or in response to acute stress. We conclude that CSI exposure during adolescence leads to persistent changes in exploratory behavior and gene expression in the hippocampus, but it does not alter the response to acute stress challenges in adulthood and is unlikely to alter the function of the noradrenergic system.

Acute Stress Response Profiles in Health Workers Facing SARS-CoV-2

ObjectiveThe study is an explorative investigation aimed to assess the differences in acute stress response patterns of health workers facing coronavirus disease 2019 (COVID-19) during Italy’s first lockdown.MethodsA cross-sectional investigation using convenience sampling method was conducted in Italy during April 2020. Eight hundred fifty-eight health workers participated in the research filling out self-report measures including Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), Insomnia Severity Index (ISI), and Impact of Event Scale–Revised (IES-R).ResultsModerate/severe depression was found in 28.9% (95% CI, 25.8–32.04), moderate/severe anxiety in 55.4% (95% CI, 51.9–58.8), insomnia in 15% (95% CI, 12.5–17.5), and distress in 52.5% (95% CI, 48.5%–56.6) of participants. The 3% of health workers reported frequent suicidal thoughts. Female sex, working for >15 h/week in a COVID-19 unit, and living apart from family were associated with a significantly higher risk of distress, anxiety, insomnia, depression, and functional impairment. Four profiles were identified on the basis of psychopathological measures: Profile_0 included 44% (N = 270); Profile_1, 25.6% (N = 157); Profile_2, 19.1% (N = 117); and Profile_3, 11.3% (N = 69) of participants. Results showed a significant effect for Profiles X IES-R (η2 = 0.079; f = 0.29), indicating that in all profiles, except for Profile_0, avoidance scale is lower than hyperarousal and intrusion symptoms scales of the IES-R. This characteristic could be a probable index of the control exerted by the responders to not fly away from their job.ConclusionThe identification of specific profiles could help psychiatrists and emergency psychologists to build specific interventions in terms of both primary and secondary prevention to face future waves of the COVID-19 outbreak.