[Notch1/Akt/Foxo1 Pathway Regulated by Kisspeptin Is Involved in Endometrial Decidualization in Patients With Recurrent Spontaneous Abortion]. / kisspeptin调控Notch1/Akt/Foxo1é€šè·¯å‚ä¸Žå¤å‘æ€§æµäº§æ‚£è€ å­å®«å† è†œèœ•è†œåŒ–.

Objective: Kisspeptin, a protein encoded by the KISS1 gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway, which assumes a central role in maintaining cellular homeostasis. In the specific context of this investigation, the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization. This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway, aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion (RSA). Methods: We enrolled a cohort comprising 45 individuals diagnosed with RSA, who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020. On the other hand, an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included. To comprehensively assess the molecular landscape, Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin (and its gene KISS1), IGFBP1 (an established marker of decidualization), Notch1, Akt, and Foxo1 within the decidua. Human endometrial stromal cells (hESC) were given targeted interventions, including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10 (the bioactive fragment of kisspeptin), and were subsequently designated as the siKP group or the KP10 group, respectively. A control group comprised hESC was transfected with blank siRNA, and cell proliferation was meticulously evaluated with CCK8 assay. Following in vitro induction for decidualization across the three experimental groups, immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups. Furthermore, RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1, Notch1, Akt, and Foxo1 across the three cell groups. Subsequently, decidualization was induced in hESC by adding inhibitors targeting Notch1, Akt, and Foxo1. The expression profiles of the aforementioned proteins and genes in the four groups were then examined, with hESC induced for decidualization without adding inhibitors serving as the normal control group. To establish murine models of normal pregnancy (NP) and RSA, CBA/J×BALB/c and CBA/J×DBA/2 mice were used. The mice were respectively labeled as the NP model and RSA model. The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234 (acting as a blocker) and were designated as RSA-KP10 and NP-KP234 groups. On the other hand, the control groups received intraperitoneal injections of normal saline (NS) and were referred to as RSA-NS and NP-NS groups. Each group comprised 6 mice, and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes. Results: The analysis revealed that the expression levels of kisspeptin, IGFBP1, Notch1, Akt, and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP (P<0.01 for kisspeptin and P<0.05 for IGFBP1, Notch1, Akt, and Foxo1). After the introduction of kisspeptin10 to hESC, there was an observed enhancement in decidualization capability. Subsequently, the expression levels of Notch1, Akt, and Foxo1 showed an increase, but they decreased after interference with KISS1. Through immunofluorescence analysis, it was observed that proliferative hESC displayed a slender morphology, but they transitioned to a rounder and larger morphology post-decidualization. Concurrently, the expression of Notch1 increased, suggesting enhanced decidualization upon the administration of kisspeptin10, but the expression decreased after interference with KISS1. Further experimentation involved treating hESC with inhibitors specific to Notch1, Akt, and Foxo1 separately, revealing a regulatory sequence of Notch1/Akt/Foxo1 (P<0.05). In comparison to the NS group, NP mice administered with kisspeptin234 exhibited increased fetal absorption rates (P<0.001) and decreased expression of IGFBP1, Notch1, Akt, and Foxo1 (P<0.05). Conversely, RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates (P<0.001) and increased expression levels of the aforementioned molecules (P<0.05). Conclusion: It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade. A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization, which in turn might contribute to the development or progression of RSA.

Association between hospital procedure volume, socioeconomic status, comorbidities, and adverse events related to surgical abortion: A nationwide population-based cohort study.

BACKGROUND: Limited evidence exists on the influence of hospital procedure volume, socioeconomic status, and comorbidities on surgical abortion outcomes. OBJECTIVE: Our study aimed to assess the association between hospital procedure volume, individual and neighborhood deprivation, comorbidities, and abortion-related adverse events. STUDY DESIGN: A nationwide population-based cohort study of all women hospitalized for surgical abortion was conducted from January 1, 2018, to December 31, 2019 in France. Annual hospital procedure volume was categorized into four levels based on spline function visualization: very low (<80), low ([80-300[), high ([300-650[), and very high-volume (≥650) centers. The primary outcome was the occurrence of at least one surgical-related adverse event, including hemorrhage, retained products of conception, genital tract and pelvic infection, transfusion, fistulas and neighboring lesions, local hematoma, failure of abortion, admission to an intensive care unit or death. These events were monitored during the index stay and during a subsequent hospitalization up to 90 days. The secondary outcome encompassed general adverse events not directly linked to surgery. RESULTS: Of the 112,842 hospital stays, 4,951 (4.39%) had surgical-related adverse events and 256 (0.23%) had general adverse events. The multivariate analysis showed a volume-outcome relationship, with lower rates of surgical-related adverse events in very high-volume (2.25%, aOR=0.34, 95%CI [0.29-0.39], p<0.001), high-volume (4.24%, aOR=0.61, 95%CI [0.55-0.69], p<0.001), and low-volume (4.69%, aOR=0.81, 95%CI [0.75-0.88], p<0.001) when compared to very low-volume centers (6.65%). Individual socioeconomic status (aOR=1.69, 95%CI [1.47-1.94], p<0.001), neighborhood deprivation (aOR=1.31, 95% CI [1.22-1.39], p<0.001), and comorbidities (aOR=1.79, 95%CI [1.35-2.38], p<0.001) were associated with surgical-related adverse events. Conversely, the multivariate analysis of general adverse events did not reveal any volume-outcome relationship. CONCLUSION: The presence of a volume-outcome relationship underscores the need for enhanced safety standards in low-volume centers to ensure equity in women's safety during surgical abortions. However, our findings also highlight the complexity of this safety concern which involves multiple other factors including socioeconomic status and comorbidities that policymakers must consider.

Complete tubal abortion which didn't require salpingectomy.

Tubal abortion is characterized by the extrusion of the foetus into the abdominal (peritoneal) cavity. It can either be a complete extrusion or incomplete with residual tissue remaining in the fallopian tube. It is a type of ectopic pregnancy that is difficult to determine the exact incidence of tubal pregnancies. Identifying cases of tubal abortions is crucial for individualized care since it can lead to a more conservative treatment approach. The diagnosis should be based on ultrasound imaging, b-hCG levels and visual conformation during exploratory surgery, either open or laparoscopic. The article describes the case of a 30-year old patient who presented with lower abdominal pain and was admitted for a suspected ectopic pregnancy. Ultrasound imaging showed a mass resembling a tubal pregnancy next to the uterus with b-hCG levels of 111.8 U/L. During laparoscopic surgery, a tubal abortion was detected in the pouch of Douglas (Rectouterine pouch). This finding led us to preserve both fallopian tubes. Histopathology confirmed our clinical findings. A conservative approach can be sufficient in case of tubal abortions, which can lead to preserved fertility and tubal functions.

Exposure to golimumab during pregnancy: Results from the Company's global safety database.

Data on the use of golimumab (GLM) during pregnancy are limited. This study evaluated pregnancy outcomes in women treated with GLM during pregnancy. Cumulative data on GLM-exposed pregnancies from the Company's global safety database (GSD) are summarized. Cases were medically confirmed maternal exposures to GLM during pregnancy or within 3 months prior to conception with a reported pregnancy outcome. Pregnancy outcomes (e.g., live births) and congenital anomalies in prospectively reported cases (i.e., pregnancy outcome not known when first reported to the company) are presented in a descriptive manner. As of May 31, 2022, 261 prospectively reported pregnancies exposed to GLM were reported in the GSD: 214 (82.0%) live births (including six sets of twins), 31 (11.9%) spontaneous abortions (including one set of twins), 13 (5.0%) induced/elective abortions, 2 (0.8%) reported intrauterine death/still birth, and 1 (0.4%) fetal adverse event in an ongoing pregnancy. The majority of pregnancies had exposure to GLM at least in the first trimester of pregnancy. In total, seven congenital anomalies (7/261; 2.7%) were reported. Of these seven congenital anomalies, five were considered major according to EUROCAT classification version 1.4. Among the five prospectively reported congenital anomalies noted in live births (5/214; 2.3%), four were classified as major (4/214; 1.8%). The rates of adverse pregnancy outcomes and major congenital anomalies in prospectively reported pregnancy cases with exposure to GLM in the Company's GSD were consistent with published background rates for the general population.

Study on the correlation between endometriosis and adverse pregnancy outcomes.

OBJECTIVE: This study aims to investigate the correlation between endometriosis (EMS) and adverse obstetric outcomes. METHODS: In this retrospective study 2,925 cesarean section cases were analyzed at the Women and Children's Hospital of Ningbo University, Department of Obstetrics, between May 2019 and December 2023. The study included 1,363 women diagnosed with endometriosis during pregnancy at the time of surgery (study group) and 1,562 women without such a diagnosis (control group). The comparative assessment covered the age of first-time mothers, number of pregnancies and births, gestational age at delivery, incidence rates of assisted reproductive technology (ART), spontaneous abortion, preterm birth, placenta previa, placental adhesion, and postpartum hemorrhage. RESULTS: The study group demonstrated a higher average age of first-time mothers, fewer pregnancies and births, and a significantly shorter gestational age at delivery (P < 0.05) compared to the control group. Incidences of primary infertility, spontaneous abortion, and ART utilization were higher in the study group. The occurrence of placenta previa, placental adhesion, and postpartum hemorrhage was also higher in the study group, indicating significant statistical differences (P < 0.05). No significant difference was observed in preterm birth rates between the groups (P > 0.05). CONCLUSION: Pregnancy in women with endometriosis is associated with a higher likelihood of adverse outcomes, therefore highlighting the need for increased clinical awareness.

Outbreak of aflatoxicosis in a dairy herd induced depletion in milk yield and high abortion rate in Pakistan.

This case report investigated the outbreak of aflatoxicosis in a dairy herd in Pakistan, which resulted in 30 abortions of 40 confirmed (75%) pregnant cows in a period of 35 days and in 18.8% depression of farm average milk production for the entire herd. The analysis of the concentrate feed of the total mixed ration (TMR), using enzyme-linked immunosorbent assay (ELISA) procedures from two different local laboratories, indicated concentrations of 60 µg/kg dry matter (DM) of aflatoxin B1 (AFB1) and 100 µg/kg DM of total aflatoxins (AFs: sum of B1, B2, G1 and G2). Subsequently, a confirmatory analysis with a more sensitive and validated multi-metabolite liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was performed. This analysis detected a concentration of total AFs in the TMR of 166 µg/kg DM ± 3.5 (AFB1:134, AFB2:17.4 and AFM1:14.9 µg/kg DM). The concentrate feed (55% of the TMR DM) was confirmed as a source of contamination, presenting a concentration >29 times higher than the EU-maximum limit value (5.68 µg/kg DM). Additionally, the multi-mycotoxin analysis evidenced the co-occurrence of 81 other toxic and potentially toxic fungal metabolites in the fed TMR. After replacing the contaminated concentrate feed with feedstuffs of the same formulation but from a new charge of ingredients, the abortion episodes ceased, and milk production increased significantly. In conclusion, the data of this case report suggest that AFs may be associated with pregnancy losses in dairy cattle and milk production depression. From the public health perspective, the data also indicate the need for a more careful examination of dairy animal feed in Pakistan. Since the high concentration of AFB1 detected in feed and considering the literature-reported transfer rates (1-6%) of this toxin to AFM1 (carcinogen for humans) in milk, the milk produced during the outbreak period is expected to be contaminated with AFM1, which raises public health concerns.

Mechanisms underlying the therapeutic effects of Semen cuscutae in treating recurrent spontaneous abortion based on network pharmacology and molecular docking.

Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development. Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression. Results: Ten compounds and 128 target genes were screened from SC, of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression. Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi.

Prognosis of remaining fetus in twin pregnancy after demise of one fetus according to its location.

BACKGROUND: To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus. METHODS: This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed. RESULTS: A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery. CONCLUSIONS: When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.

Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.

STUDY QUESTION: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester? SUMMARY ANSWER: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages. WHAT IS KNOWN ALREADY: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL. STUDY DESIGN, SIZE, DURATION: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals. PARTICIPANTS/MATERIALS, SETTING, METHODS: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system. STUDY FUNDING/COMPETING INTEREST(S): The research received no specific funding, and the authors declare no competing interests. TRIAL REGISTRATION NUMBER: clinicaltrial.gov NCT05557201.

CXC chemokine receptor type 5 may induce trophoblast dysfunction and participate in the processes of unexplained missed abortion, wherein p-ERK and interleukin-6 may be involved.

Chemokines regulate the trophoblast dysfunction involved in the occurrence and development of pathological pregnancy, including missed abortions. In particular, CXC chemokine receptor type 5 mediates cell proliferation, migration, and inflammation; nonetheless, its role in missed abortions remains unclear. This study aimed to examine the expression of CXC chemokine receptor type 5 in missed abortions and to investigate the effects of CXC chemokine receptor type 5 on the biological behaviour of trophoblasts, as well as the underlying mechanisms. Our results indicated that CXC chemokine receptor type 5 was upregulated in the villi of women who experienced unexplained missed abortions, as compared with those who had normal pregnancies. CXC chemokine receptor type 5 inhibited the proliferation and migration of human first-trimester trophoblast/simian virus cells but promoted cell apoptosis. With respect to its mechanisms, CXC chemokine receptor type 5 activated the extracellular signal-regulated protein kinase 1/2 signalling pathway and upregulated the secretion of interleukin-6; however, it had no effect on the secretion of tumour necrosis factor-α. In conclusion, our findings suggest that CXC chemokine receptor type 5 induces trophoblast dysfunction and participates in the processes of unexplained missed abortions, wherein p-ERK and interleukin-6 may be involved.

Incidence of induced abortion among commercially insured pregnant patients with cancer.

OBJECTIVES: This study aimed to characterize pregnancy outcomes and the incidence of induced abortion among pregnant people with a diagnosis of malignancy. STUDY DESIGN: We conducted a retrospective cohort study among privately insured people aged 12 to 55 years from the fourth quarter of 2015-2020 using US claims data from Merative MarketScan Research Databases. We included pregnancies from seven states with favorable policies for private insurance coverage of abortion. RESULTS: There were 1471 of 183,685 (0.8%) pregnancies with a cancer diagnosis. Among those receiving anticancer therapy, 21.6% (95% CI: 14.4-30.4%) underwent induced abortion compared with 10.9% (95% CI: 10.8-11.1%) of pregnant patients without a cancer diagnosis. CONCLUSIONS: Abortion restrictions may affect many pregnant women requiring cancer treatment in early pregnancy.

Conflictos éticos en un contexto de gestión pública: objeción de conciencia y aborto en la red sanitaria pública española

En este artículo se sostiene, en primer lugar, que (1) la persistencia a nivel internacional de debates éticos en torno al estatus moral del nasciturus y (2) el tradicional compromiso deontológico de los profesionales sanitarios con la salud, tanto de la embarazada como del hijo que espera, dotan de pleno sentido y vigencia al derecho a la objeción de conciencia de dichos profesionales. Sin embargo, donde el aborto legal se configura como prestación sanitaria, surge entonces la dificultad de gestionar esa prestación y, al tiempo, el conflicto moral que expresa la objeción de conciencia. Si en una institución sanitaria pública la objeción es generalizada, se plantea una disyuntiva con implicaciones éticas entre derivar a las gestantes a otras instituciones o aplicar estrategias de integración de personal a nivel de servicio de salud. En el caso de España, se ha aprobado este año una reforma de la Ley Orgánica de salud sexual y reproductiva y de la interrupción voluntaria del embarazo (LOSSRIVE), que manifiesta una voluntad más taxativa de que la objeción de conciencia no impida el acceso al aborto en las instituciones sanitarias públicas, estableciéndose previsiones específicas al efecto. A partir de los trabajos parlamentarios identificamos los principales puntos de discrepancia política que remiten a dispares posiciones de fondo sobre el aborto y afectan al propio planteamiento de la reforma, así como a otros elementos no siempre novedosos -algunos de ellos ya estaban en la LOSSRIVE o se venían aplicando a nivel autonómico con el plácet del Constitucional.

This article argues, first, that (1) the persistence at the international level of ethical debates on the moral status of nasciturus and (2) the traditional ethical commitment of health professionals to the health of both the pregnant woman and the unborn child, give full sense and validity to the right to conscientious objection of these professionals. However, where legal abortion is configured as a health care service, the difficulty of managing this service and, at the same time, the moral conflict expressed by conscientious objection arises. If, in a public health institution, objection is widespread, there is a dilemma with ethical implications between referring pregnant women to other institutions or implementing staff integration strategies at the health service level. In the case of Spain, a reform of the Organic Law on Sexual and Reproductive Health and the Voluntary Interruption of Pregnancy (LOSSRIVE) was approved this year, which shows a more stringent willingness that conscientious objection does not prevent access to abortion in public health institutions, establishing specific provisions to that effect. Based on the parliamentary work, we identified the main points of political discrepancy, which remit to different basic positions on abortion and affect the very approach of the reform, as well as other not always new elements -some of them were already in the LOSSRIVE or were already being applied at the regional level with the approval of the Constitutional Court.

Este artigo argumenta, em primeiro lugar, que (1) a persistência, em nível internacional, de debates éticos sobre o status moral do nascituro e (2) o tradicional compromisso deontológico dos profissionais de saúde com a saúde da gestante e do filho que ela espera, dão pleno sentido e vigência ao direito à objeção de consciência desses profissionais. Entretanto, quando o aborto legal é configurado como um serviço de saúde, surge a dificuldade de gerir esse serviço e, ao mesmo tempo, gerir o conflito moral expresso pela objeção de consciência. Se, em uma instituição de saúde pública, a objeção for generalizada, haverá uma escolha com implicações éticas entre encaminhar as gestantes a outras instituições ou aplicar estratégias de integração de pessoal no nível do serviço de saúde. No caso da Espanha, foi aprovada este ano uma reforma da Lei Orgânica de Saúde Sexual e Reprodutiva e a Interrupção Voluntária da Gravidez (LOSSRIVE) que expressa uma vontade mais constrangedora de garantir que a objeção de consciência não impeça o acesso ao aborto em instituições públicas de saúde, estabelecendo disposições específicas para esse fim. Com base no trabalho parlamentar, identificamos os principais pontos de discrepância política, que remetem a diferentes posições de fundo sobre aborto e afetam a própria aproximação da reforma, assim como outros elementos que nem sempre são novos -alguns deles já estavam no LOSSRIVE ou já estavam sendo aplicados em nível regional com a aprovação do Tribunal Constitucional-.

Democracia representativa: uma leitura interseccional sobre a atuação legislativa da Frente Parlamentar de Combate ao Aborto ­ "Pró-vida", no Estado de Goiás / Representative democracy: An intersectional review of the legislative action of the Parliamentary Front to Combat Abortion ­ "Pro-life", in the State of Goiás / Democracia representativa: Una revisión interseccional de la acción legislativa del Frente Parlamentario de Lucha contra el Aborto ­ "Provida", en el Estado de Goiás

Objetivo: Analisar, a partir da perspectiva crítica e interseccional, a organização, composição e atuação legislativa de comissão voltada aos direitos sexuais e reprodutivos de mulheres, denominada Frente Parlamentar de Combate ao Aborto ­ Pró-Vida. Metodologia: Foi realizada leitura interseccional acerca da constituição de Frente Parlamentar de Combate ao Aborto - "Pró-Vida", da Assembleia Legislativa do Estado de Goiás (ALEGO), e o perfil sociodemográfico de seus integrantes foi traçado, discutido a luz dos marcadores sociais gênero, raça/etnia, classe social e religião, e problematizado acerca de um tema que implica diretamente na saúde e na vida das mulheres, o aborto. Resultados e Discussão: a análise dos resultados aponta a sub-representividade feminina, a prevalência de pessoas brancas e o predomínio de ideologia conservadora nos costumes e religião no perfil sociodemográfico dos membros integrantes da frente parlamentar estudada. Em contraponto, a literatura, ao discutir os marcadores sociais em investigação, traz o retrato daquelas que optam por realizar o aborto como sendo o de mulheres negras, de baixa renda e escolaridade, e que procuram em partidos de viés progressista advocacia para suas causas. Conclusão: A estrutura tradicional, presente na frente parlamentar investigada, enfrenta desafios na construção de um debate representativo e capaz de reproduzir nas políticas públicas as complexas identidades, necessidades e experiências das mulheres em risco de abortamento. Nessa argumentação, a construção de práticas políticas e tratos legislativos devem, prioritariamente, considerar as complexidades identitárias e as intersecções e opressões que levam as mulheres ao aborto para, enfim, construir-se uma democracia inclusiva, equitativa e representativa.

Objective: Analyze, from a critical and intersectional perspective, the organization, composition and legislative performance of a commission focused on women's sexual and reproductive rights, called the Parliamentary Front to Combat Abortion ­ Pró-Vida. Methodology: An intersectional reading was carried out regarding the constitution of the Parliamentary Front to Combat Abortion - "Pró-Vida", of the Legislative Assembly of the State of Goiás (ALEGO), and the sociodemographic profile of its members was outlined, discussed in light of social markers, gender, race/ethnicity, social class and religion and problematized about a topic that directly affects women's health and lives, abortion. Results and discussion: analysis of the results points to female underrepresentation, the prevalence of white people and the predominance of conservative ideology in customs and religion in the sociodemographic profile considered. In contrast, the literature, when discussing the social markers under investigation, portrays those who choose to have an abortion as black women, with low income and education, and who look to parties with a progressive bias to advocate for their causes. Conclusion: The traditional structure present in the Parliamentary Front investigated faces challenges in building a representative debate capable of reproducing in public policies the complex identities, needs and experiences of women at risk of miscarriage. In this argument, the construction of political practices and legislative approaches must primarily consider the complexities of identity and the intersections and oppressions that lead women to abortion in order to, ultimately, build an inclusive, equitable and representative democracy.

Objetivo: Analizar, desde una perspectiva crítica e interseccional, la organización, composición y desempeño legislativo de una comisión enfocada en los derechos sexuales y reproductivos de las mujeres, denominada Frente Parlamentario de Lucha contra el Aborto ­ Pró-Vida. Metodología: Se realizó una lectura interseccional sobre la constitución del Frente Parlamentario de Lucha contra el Aborto - "Pró-Vida", de la Asamblea Legislativa del Estado de Goiás (ALEGO), y se delineó el perfil sociodemográfico de sus integrantes, discutido a la luz de marcadores sociales, género, raza/etnia, clase social y religión y problematizados sobre un tema que afecta directamente la salud y la vida de las mujeres, el aborto. Resultados y discusión: el análisis de los resultados apunta a la subrepresentación femenina, el predominio de personas blancas y el predominio de la ideología conservadora en las costumbres y la religión en el perfil sociodemográfico considerado. En contraste, la literatura, al discutir los marcadores sociales bajo investigación, retrata a quienes eligen abortar como mujeres negras, con bajos ingresos y educación, y que buscan partidos con un sesgo progresista para defender sus causas. Conclusión: La estructura tradicional presente en el Frente Parlamentario investigado enfrenta desafíos en la construcción de un debate representativo capaz de reproducir en políticas públicas las complejas identidades, necesidades y experiencias de las mujeres en riesgo de aborto espontáneo. En este argumento, la construcción de prácticas políticas y enfoques legislativos debe considerar principalmente las complejidades de la identidad y las intersecciones y opresiones que llevan a las mujeres al aborto para, en última instancia, construir una democracia inclusiva, equitativa y representativa.

[Effect of Shoutai Pills on expression of key glycolytic proteins and apoptosis related factors at maternal fetal interface in mouse model of threatened abortion with syndrome of kidney deficiency].

This study aims to explore the mechanism of Shoutai Pills in treating threatened abortion. According to the random number table method, ICR female mice were randomized into a normal group, a model group, a dydrogesterone group, and a Shoutai Pills group, with 15 mice in each group. Mice were administrated with normal saline(normal and model groups) or the suspension of Shoutai Pills or dydrogesterone by gavage at 9:00 am every day. At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days. ICR female and male mice were caged in a ratio of 2∶1 during the pre-estrous or estrous period. From the first day of pregnancy, drug administration was continued for 5 consecutive days. On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion. On day 6 of pregnancy, 10 female ICR mice were randomly selected from each group, and the uterus was collected for observation of the pathological changes of trophoblasts at the maternal-fetal interface by hematoxylin-eosin(HE) staining. The protein levels of key enzymes of glycolysis, hexokinase 2(HK2), enolase 1(ENO1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A(LDHA), were determined by Western blot and immunofluorescence. The expression of apoptosis-related proteins including B cell lymphoma-2(Bcl-2), Bcl-2-associated protein X(Bax), and cysteinyl aspartate-specific proteinase-3(caspase-3) was determined by Western blot and real-time PCR. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling was employed to examine apoptosis. The embryo loss rate of the remaining five female mice was calculated by trypan blue staining method on day 14 of pregnancy. On day 14 of pregnancy, the embryo loss rate of the normal group was 5.00%, which was lower than that(27.78%) in the model group(P<0.05). Dydrogesterone and Shoutai Pills groups showed reduced embryo loss rates(10.26% and 7.50%, respectively) compared with the model group. On day 6 of pregnancy, compared with the normal group, the model group showed down-regulated expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and up-regulated expression of Bax and caspase-3(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills up-regulated the expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and down-regulated the expression of Bax and caspase-3(P<0.05). Compared with that in the normal group, the apoptosis rate in the model group increased(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P<0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.

Pregnancy, abortion, and birth control methods' complicity with breast cancer occurrence.

Reproductive factors play significantly important roles in determining the breast cancer (BC) risk. The impact of pregnancy, abortion, and birth control methods on tumor development remains unclear. It has been found that early full-term pregnancies in young women can lower their lifetime risk of developing the type of cancer in question. However, having a first full-term pregnancy at an older age can increase this risk. The relationship between pregnancy and breast cancer (BC) is, however, much more complicated. Both induced and spontaneous abortions lead to sudden changes in hormonal balance, which could cause different effects on sensitive breast epithelial cells, making abortion a potential risk factor for breast cancer. The influence of hormonal contraception on carcinogenesis is not comprehensively understood, and therefore, more exhaustive analysis of existing data and further investigation is needed. This review explores how the mentioned reproductive factors affect the risk of breast cancer (BC), focusing on the molecular mechanisms that contribute to its complexity. By comprehending this intricate network of relationships, we can develop new strategies for predicting and treating the disease.

Alterations in the pro-resolving lipid mediator machinery within first trimester maternal tissue: Implications in decidualization and miscarriage risk.

A pivotal event in uterine receptivity and human reproduction is the differentiation of endometrial stromal cells into decidual cells, known as decidualization. Decidualization is interlinked with its inflammatory environment. Our study aimed to investigate the presence and role of pro-resolving lipid mediators in first trimester maternal tissue. We assessed the levels of LXA4 and RvD1, along with their metabolic LOX enzymes, in elective (control) and sporadic miscarriage samples. We investigated the effects of LXA4 and RvD1 on decidualization using primary endometrial stromal cells and the immortalized endometrial stromal St-T1b cell line. The upregulation of 12- and 15-LOX expression was observed in pregnancy tissue after sporadic miscarriage, suggesting an inflammatory imbalance. Furthermore, incubation with these lipid mediators led to a decrease in decidualization biomarkers PRL and IGFBP-1, accompanied by morphological changes indicative of aberrant differentiation. The expression of LOX enzymes in decidual natural killer cells suggests their involvement in regulating the inflammatory surroundings and the extent of decidualization.

Abscisic acid induces PpeKIL1 to terminate fruit growth and promote fruit abortion in peach (Prunus persica).

Abnormal pollination from chance events or hybridization between species leads to unusual embryo development, resulting in fruit abortion. To elucidate the mechanism underlying fruit abortion, we conducted a comprehensive analysis of the transcriptome and hormone profiles in aborting fruits (AF) derived from an interspecific cross between the peach cultivar 'Huangjinmi 3' and the Prunus mume cultivar 'Jiangmei', as well as in normal-seeded fruits (NF) resulting from an intraspecific cross of 'Huangjinmi 3' with the 'Manyuanhong' peach cultivars. Growth of AF was inhibited during the exponential growth phase, with up-regulation of oxidative stress related genes and down-regulation of DNA replication and cell cycle genes. Accumulation of the tissue growth-related hormones auxin and cytokinin was reduced in AF, while levels of the growth inhibiting hormone abscisic acid (ABA) were higher compared to NF. The increased ABA concentration aligned with down-regulation of the ABA catabolism gene CYP707A2, which encodes abscisic acid 8'-hydroxylase. Correlation analysis showed ABA could explain the maximum proportion of differently expressed genes between NF and AF. We also showed that expression of KIRA1-LIKE1 (PpeKIL1), a peach ortholog of the Arabidopsis KIRA1 gene, was up-regulated in AF. PpeKIL1 promotes senescence or delays normal growth in tobacco and Arabidopsis, and its promoter activity increases with exogenous ABA treatment. Our study demonstrates a candidate mechanism where ABA induces expression of PpeKIL1, which further blocks normal fruit growth and triggers fruit abscission.

Triaging and Evaluation of Products of Conception in Abortions and Post-Partum Hemorrhage.

The proper evaluation of abortion specimens and placentas from stillbirth and post-partum cases is important for adequate clinical care of post-abortion and post-partum patients. The following topics will be reviewed: (1) the importance of evaluation of both fetal and placental tissue in first trimester abortions to confirm an intrauterine pregnancy versus an ectopic pregnancy; (2) the clinical history associated with an abortion specimen or retained products of conception (POC) influences how the pathologist should triage the specimen; (3) the criteria for diagnosis of a molar pregnancy, which is critical for clinicians to know which patients need follow-up; (4) the utility of genetic studies for both diagnosis and appropriate follow-up of the patient; and (5) the pathologic evaluation of specimens from patients with post-partum hemorrhage for placenta accreta spectrum and subinvolution of maternal vessels.

The in vitro mechanism of Vaspinregulates the proliferation and steroidogenesis of rat lutein cells.

OBJECTIVE: Stable luteal cell function is an important prerequisite for reproductive ability and embryonic development. However, luteal insufficiency seriously harms couples who have the desire to have a pregnancy, and the most important thing is that there is no complete solution. In addition, Vaspin has been shown to have regulatory effects on luteal cells, but the complex mechanisms involved have not been fully elucidated. Therefore, this study aimed to explore the effect of Vaspin on rat luteal cells and its mechanism. METHODS: Granulosa lutein cells separated from the ovary of female rats were incubated for 24h with gradient concentrations of Vaspin, and granulosa lutein cells incubated with 0.5% bovine serum albumin were used as controls. The proliferation, apoptosis, angiogenesis, progesterone (P4) and estradiol (E2) were detected by CCK-8, Anneixn-FITC/PI staining, angiogenesis experiment and ELISA. Western blot was applied to observe the expression levels of proteins related to cell proliferation, apoptosis, angiogenesis and MEK/MAPK signaling pathway. RESULTS: Compared with the Control group, Vaspin could significantly up-regulate the proliferation of granulosa lutein cells and reduce the apoptosis. Moreover, Vaspin promoted the angiogenesis of granulosa lutein cells and the production of P4 and E2 in a concentration-dependent manner. Furthermore, Vaspin up-regulated the CyclinD1, CyclinB1, Bcl2, VEGFA and FGF-2 expression in granulosa lutein cells, and down-regulated the level of Bax. Also, Vaspin increased the p-MEK1 and p-p38 levels. CONCLUSION: Vaspin can up-regulate the proliferation and steroidogenesis of rat luteal cells and reduce apoptosis, which may be related to the influence of MEK/MAPK activity.

Case report: Findings in ovaries development from an aborted equine fetus.

An aborted female foal was submitted for necropsy. During the gross examination, the ovaries were pale, grayish, and enlarged (6 × 5 cm), with a well-developed vascular structure surrounding the external surface; the cut surface of the ovaries showed a brownish parenchyma with white follicular areas mainly localized in the peripheral region. The ovaries were fixed for histological investigations. The histological evaluation of the ovaries showed polygonal-shaped cells with abundant cytoplasm and round or oval nuclei, arranged in cords of single cells. The tissue architecture was characterized by the presence of lobular-like tissues with a central vein. The tissue mimicking hepatocytes was delimited by a mature fibrous tissue and was surrounded by the normal ovarian tissue characterized by germinal epithelium and primordial follicular structures. Based on the histological findings, a diagnosis of bilateral ovarian hamartoma was carried out initially. For a better characterization of the ovarian tissue, the expression of tissue-specific (liver and ovary) markers was investigated using immunohistochemistry. Following the immunohistochemical analysis, the hamartoma diagnosis was excluded. The ovaries exhibited unique characteristics different from those of adult horse ovaries as well as unique morphological features different from other mammalian species. This case report enhances our understanding of ovaries at a later stage of pregnancy and unveils unique characteristics of horse ovaries development, avoiding misdiagnosis with pathological findings, hamartomas, or neoplasia.