BackgroundRecurrent pregnancy loss (RPL), defined as 3 or more consecutive miscarriages, is widely attributed either to repeated chromosomal instability in the conceptus or to uterine factors that are poorly defined. We tested the hypothesis that abnormal cyclic differentiation of endometrial stromal cells (ESCs) into specialized decidual cells predisposes to RPL, based on the observation that this process may not only be indispensable for placenta formation in pregnancy but also for embryo recognition and selection at time of implantation.Methodology/Principal FindingsAnalysis of mid-secretory endometrial biopsies demonstrated that RPL is associated with decreased expression of the decidual marker prolactin (PRL) but increased levels of prokineticin-1 (PROK1), a cytokine that promotes implantation. These in vivo findings were entirely recapitulated when ESCs were purified from patients with and without a history of RPL and decidualized in culture. In addition to attenuated PRL production and prolonged and enhanced PROK1 expression, RPL was further associated with a complete dysregulation of both markers upon treatment of ESC cultures with human chorionic gonadotropin, a glycoprotein hormone abundantly expressed by the implanting embryo. We postulated that impaired embryo recognition and selection would clinically be associated with increased fecundity, defined by short time-to-pregnancy (TTP) intervals. Woman-based analysis of the mean and mode TTP in a cohort of 560 RPL patients showed that 40% can be considered “superfertile”, defined by a mean TTP of 3 months or less.ConclusionsImpaired cyclic decidualization of the endometrium facilitates implantation yet predisposes to subsequent pregnancy failure by disabling natural embryo selection and by disrupting the maternal responses to embryonic signals. These findings suggest a novel pathological pathway that unifies maternal and embryonic causes of RPL.
BackgroundPregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown.Methodology/Principal FindingsWe employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1β, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo.ConclusionsHuman ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies.
The legacy of colonial rule has permeated into all aspects of life and contributed to healthcare inequity. In response to the increased interest in social justice, medical educators are thinking of ways to decolonise education and produce doctors who can meet the complex needs of diverse populations. This paper aims to explore decolonising ideas of healing within medical education following recent events including the University College London Medical School’s Decolonising the Medical Curriculum public engagement event, the Wellcome Collection’s Ayurvedic Man: Encounters with Indian Medicine exhibition and its symposium on Decolonising Health, SOAS University of London’s Applying a Decolonial Lens to Research Structures, Norms and Practices in Higher Education Institutions and University College London Anthropology Department’s Flourishing Diversity Series. We investigate implications of ‘recentring’ displaced indigenous healing systems, medical pluralism and highlight the concept of cultural humility in medical training, which while challenging, may benefit patients. From a global health perspective, climate change debates and associated civil protests around the issues resonate with indigenous ideas of planetary health, which focus on the harmonious interconnection of the planet, the environment and human beings. Finally, we look further at its implications in clinical practice, addressing the background of inequality in healthcare among the BAME (Black, Asian and minority ethnic) populations, intersectionality and an increasing recognition of the role of inter-generational trauma originating from the legacy of slavery. By analysing these theories and conversations that challenge the biomedical view of health, we conclude that encouraging healthcare educators and professionals to adopt a ‘decolonising attitude’ can address the complex power imbalances in health and further improve person-centred care.
The objective of this trial was to investigate whether 500 microg oral misoprostol given immediately after delivery of the neonate at Caesarean section is as effective as a bolus intravenous injection of 10 iu Syntocinon in stimulating uterine contractions and thereby reducing blood loss. Forty women undergoing elective or emergency Caesarean section were included in a placebo-controlled randomised trial. Group 1 received oral misoprostol and a placebo intravenous bolus and Group 2 received intravenous Syntocinon and oral placebo tablets. The main outcome measures were estimated blood loss at Caesarean section, drop in serum haemoglobin, and the need for additional uterotonic agents. We found that there was no significant difference (p = 0.75) in estimated blood loss between the two groups. No differences were observed in the decrease in haemoglobin, requirement for additional oxytocics, the need for blood transfusion or the degree of shivering in each group (p > 0.05 in each case). We concluded that oral misoprostol could be used as an alternative oxytocic agent for the third stage at Caesarean section. However, there is an obvious need for a larger randomised controlled trial to be undertaken. Previous published studies have concentrated on vaginal births and further studies should be extended to Caesarean deliveries.
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