Obstetric Disorders Research Articles

Hypoxia‐Induced Syndecan 1 Shedding in Placental Trophoblasts is Associated with Increased Peroxide

Preeclampsia is one of the most common obstetrical disorders, affecting ~5% of pregnancies. It is one of the leading causes of maternal and fetal morbidity and mortality, as well as premature birth. While the origins of preeclampsia are obscure, it is believed that many cases are due to placental insufficiency and resulting ischemia/hypoxia. While many of the factors released by the ischemic placenta are known, the full scope of the molecular effects of ischemia on the placenta are not known. We have recently demonstrated that hypoxia causes shedding of the placental extra cellular matrix in vitro and in vivo, particularly the glycoprotein syndecan 1. It has also been reported that vascular ECM shedding can be affected by reactive oxygen species. Therefore, we wished to test the hypothesis that oxidative stress is the mediator of placental syndecan 1. We treated placental trophoblast derived cells (BeWo) for 24 hours with oxygen conditions mimicking healthy (8%) or ischemic (1%) placentas. To determine the effect of hypoxia on peroxide production, we used the peroxide indicator amplex red. In response to hypoxic conditions, amplex fluorescence was significantly increased (6728 ± 196 vs 8201 ± 501 AU, p<0.05), which was attenuated with the peroxide scavenger apocynin (4626 ± 100 AU, p>0.05). In response to hypoxia, SDC1 released from BeWos increased significantly (175 ± 10 vs 280 ± 13 pg/ml, p<0.05). There was no effect of the peroxide scavenger apocynin in normoxic conditions, but there was a significant reduction (185 ± 10 pg/ml, p<0.05) in hypoxic conditions. These data suggest that peroxide is a key mediator of hypoxia‐induced shedding of SDC‐1, and could play a key role in ECM shedding in placental ischemia in vivo. Future studies will examine the in vivo effects of peroxide scavenging on SDC shedding as well as its effects on other ECM components.Support or Funding InformationThis work was supported in part by NIH grants P01HL51971, P20GM104357, and R01HL137791

Comparison of Maternal and Perinatal Outcomes in Women With Super Obesity Based on Planned Mode of Delivery

(Aust N Z J Obstet Gynaecol. 2019;59:387–393) Guidelines on preferred delivery methods for pregnant women with super obesity are currently nonexistent. These women are more likely to have medical comorbidities and develop obstetric disorders such as gestational diabetes and preeclampsia. In addition, urgent cesarean delivery may be fraught with anesthetic and surgical challenges. As a result, these women are more likely to undergo an elective cesarean section (CS) despite a lack of evidence to support this approach. The current study was undertaken to compare outcomes based on the planned mode of delivery. The investigators also sought to identify factors that could predict a successful vaginal delivery.

Genetic susceptibility analysis of GCLC rs17883901 polymorphism to preeclampsia in Chinese Han women

Preeclampsia (PE) is a specific obstetric disorder that may result in maternal and neonatal morbidity and mortality. Increasing evidence has been indicated that some candidate genes related to oxidative stress, such as glutamate-cysteine ligase, catalytic subunit (GCLC), glutamate-cysteine ligase, modifier subunit (GCLM), involve in the pathogenesis of PE. After the genetic contribution of GCLC rs17883901 polymorphism was analyzed by TaqMan allelic discrimination real-time PCR in 1001 PE patients and 1182 normal pregnant women, a case-control association analysis was performed. Although no statistical difference was found in genetic distribution of rs17883901 in GCLC between PE and control group (χ2 = 2.201, p = .333 by genotypic, χ2 = 0.524, p = .469, OR = 0.932, 95%CI = 0.771–1.128 by allelic), significant differences in the genotypic frequencies were investigated between mild PE group (χ2 = 6.999, p = .030) or late-onset PE group (χ2 = 6.197, p = .045) and control group. Furthermore, when dividing the mild PE patients, the late-onset PE patients and the controls into TT/CT + CC, TT + CT/CC, and TT/CC subgroups, we found statistical differences between mild PE and controls (TT/CT + CC:χ2 = 5.132, p = .023, OR = 2.948, 95%CI = 1.107–7.854; TT/CC:χ2 = 4.564, p = .033, OR = 2.793, 95%CI = 1.046–7.460) as well as late-onset PE and controls (TT/CT + CC:χ2 = 4.043, p = .044, OR = 2.248, 95%CI = 1.000–5.055). This is the first study to indicate GCLC rs17883901 polymorphism may be associated with a risk of mild PE and late-onset PE in Chinese Han women. However, additional well-designed studies with multi-ethnic and large-scale samples should be performed to validate our results.

Prevalence of gynecological and obstetric disorders in patients associated with thyroid dysfunction

Thyroid gland is the most vital endocrine gland which plays a major role in growth, development and metabolism of human body. Thyroid dysfunction is an important causative factor of gynecological and obstetric abnormalities. This is an observational study conducted at Obstetrics and Gynecology department of a private hospital in Warangal district. A total of 60 patients were recruited in the present study after satisfying all inclusion and exclusion criteria. Among 255 patients with gynecological complaints, 195 patients (76 %) were euthyroid, 59 patients (23 %) were hypothyroid and 1 patient (01 %) had hyperthyroidism. Among 60 patients with thyroid dysfunction, the most common menstrual disorder observed was oligomenorrhoea. Predominant gynecological disorders associated with thyroid dysfunction were PCOS and Fibroid uterus (51 %). The most common obstetric conditions associated with thyroid disorders are Pregnancy Induced Hypertension (PIH), miscarriage and oligohydramnios all together accounting for 67 %. As thyroid disorders may accompany with alterations in menstrual and reproductive function of women, screening for thyroid dysfunction should be made an integral part of investigations and in the treatment of gynecological and obstetric disorders.

Prevalence of gynecological and obstetric disorders in patients associated with thyroid dysfunction

Prevalence of gynecological and obstetric disorders in patients associated with thyroid dysfunction

Medicinal Plants and Gyneco-obstetric Disorders among Women in the South East of Morocco

Background: Phytotherapy is used in developing countries to treat several gynecoobstetric disorders. Objective: This study aimed to collect information on herbal remedies traditionally used for the treatment of gyneco-obstetric disorders in the southeast region of Morocco (Tafilalet). Methods: Field work was undertaken as an ethnopharmacological survey involving 980 women, 60 herbalists and 20 midwives in 6 different areas of the Tafilalet region. Data was compiled using a semi-structured questionnaire via face-to-face interviews. Three quantitative ethnopharmacological indices (the use value (UV), informant consensus factor (ICF) and fidelity levels (Fl)) were calculated. Results: A total of 115 species of plants, belonging to 47 families were identified in this study. The most important species according to their use value were Rosmarinus officinalis (0.40), Lavandula angustifolia (0.35), Origanum vulgare (0.22), Cinnamomum cassia (0.18) and Phoenix dactylifera (0.15). Among the obstetric disorders, the highest ICF values were recorded for menstruation (0.95), female infertility (0.9), and maintenance of pregnancy as well as well-being of fetus (0.87). The analysis showed that the highest Fl value for menstruation was found for Origanum vulgare. (94.07 %) followed by Rosmarinus officinalis (87.29%). For female fertility, the highest Fl value was found in Phoenix dactylifera (77.50%) followed by Lepidium sativum (77.17%). Conclusion: This explorative survey emphasizes the need to preserve and document the traditional healing practices for managing gyneco-obstetric disorders and the valorization of this potential could be important for the improvement of women reproductive health.

L’accouchement tragique de Lucy ? À propos de la mortalité maternofœtale de la préhistoire à l’époque médiévale

ObjectivesSkeletal remains of pregnant woman whit fetus still in the pelvic region are scarce in the archaeological record. We aimed to review the different cases of maternal and fetal death in the ancient times. MethodsA review of literature using Medline database and Google about mortality during pregnancy in Prehistory, Antiquity and middle age. The following key words were used: ancient times; paleopathology; immature fetus; medieval; pregnancy; mummies; Antiquity; maternal mortality. ResultsThirty articles were found and we added one personal unpublished case. There were 64 female skeletons with mainly infectious abnormalities (10 dental abscesses and 2 pneumoniae) followed by traumatic lesions (2 frontal fractures and 1 femur luxation). There were 48 fetal remains and 3 twins. We noted 8 obstructed labors (3 breech presentations, 4 transverse lies and one possible shoulder dystocia). ConclusionsThe fact that there were only few cases of maternal deaths with fetal remains raises the questions of the cause of death and the relationship between death and obstetric disorders. Beside the underestimation of these archaecological cases, the reasons of both fetal and maternal death must be looking for among several diseases or anomalies of both or of one of them, related with poor environmental conditions (such as malnutrition and high morbidity from infections) and lack of care the mother and fetus need.

Эффективность вагинальной формы сочетания метронидазола и миконазола нитрата для терапии бактериального вагиноза и кандидозного вульвовагинита

Recurrent vulvovaginal infections being an epidemiological and clinical issue also have social and psychological implications. As a result, the development of the effective diagnostic strategies and therapeutic approaches to female genital infections is important. This paper reviews the most common vulvovaginal infections, i.e., bacterial vaginosis and vulvovaginal candidiasis. Topical metronidazole and miconazole vaginal dosage forms prescribed for these relevant obstetrical gynecological disorders are highlighted. Although numerous domestic and foreign publications on the clinical efficacy of this combination are available, dose reductions and the minimum therapeutically effective doses for bacterial vaginosis, vulvovaginal candidiasis, and mixed vaginitis are still challenging entities. The data on the efficacy of a novel dosage form, Gynocaps® vaginal capsules, containing low doses of miconazole (100 mg) and metronidazole (100 mg) are addressed. The treatment has resulted in microbiological cleaning, the normalization of vaginal WBC count, and the improvement of vaginal florocenosis. In addition, easy-to-use vaginal capsules ensure treatment adherence.KEYWORDS: bacterial vaginosis, vulvovaginal candidiasis, metronidazole, miconazole nitrate, vaginal capsules.FOR CITATION: Markova E.A. Efficacy of metronidazole and miconazole vaginal co-formulation for bacterial vaginosis and vulvovaginal candidiasis. Russian Journal of Woman and Child Health. 2020;3(3):205–210. DOI: 10.32364/2618-8430-2020-3-3-205-210.

Junctional zone endometrium alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment.

To investigate the JZE alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment. JZE was found to be significantly extended in patients with endometriosis, leading to the conclusion that endometriosis is a primary disease of the uterus, much like adenomyosis. Statistical correlation was then demonstrated between the severity of endometriosis and the depth of the adenomyosis infiltrates, hence the thickening of the JZE. Stem cells, predominantly found in the JZE were also found in histological sections of leiomyoma, suggested to be the origin of leiomyoma. This reservoir of JZE stem cells is influenced by different stressors leading to their differentiation into leiomyoma, endometriosis, adenomyosis or endometrial cancer, according to the stressor. The variability in presentation was hypothesized to be connected to genetic and epigenetic factors. JZE was also suggested to act as a barrier, stopping endometrial carcinoma cells invasion and metastasis. In addition, JZE plays a major role in conception, pregnancy and postpartum. JZE is an important anatomical landmark of the uterus contributing to normal uterine function under the influence of ovarian hormones. Alterations of the JZE thickness and contractility can be used as pathognomonic clinical markers in infertility and chronic pelvic pain, for subendometrial and myometrial disorders, for example, adenomyosis and fibroids. Prospective randomized control trials will clarify the diagnostic steps, imaging modalities to follow and probably triage the patients between medical and surgical treatments.

Incarceration of the gravid uterus: a case report and literature review

BackgroundIncarceration of the gravid uterus is a rare obstetric disorder that contributes to pregnancy-related complications. To understand its clinical characteristics and managements, we have reviewed the etiology, risk factors, clinical characteristics and current treatments of an incarcerated gravid uterus based on 162 cases reported in the English language literature, including our patient.Case presentationA 25-year-old primigravida, with a history of lymphatic tuberculosis, infertility due to blocked fallopian tubes and received in vitro fertilization. The patient presented with urine retention and lower abdominal pain in the early second trimester. Uterine incarceration was diagnosed based on pelvic examination and abdominal ultrasound. A Foley catheter was placed and manual reposition was successful. No episode of retention was experienced after the further enlargement of the uterus and its ascent. A healthy infant was delivered vaginally on 38th week of pregnancy.ConclusionsUterine incarceration due to pelvic adhesions is rare and, because of it non-specific clinical presentations, is often misdiagnosed. Abdominal ultrasound is instrumental for the diagnosis because it can directly image the disturbed uterine and pelvic anatomy. There are limited treatment options for uterine incarceration, but definitive diagnosis allows procedures to treat and to reduce severe complications of uterine incarceration.

Enhanced recovery after elective cesarean sections

Objective: To compare the early recovery after surgery (ERAS) pprotocol with the conventional one in women undergoing elective CS.Patients and Methods: The study included 96 women undergoing elective cesarean section for different reasons. They were randomly divided into two groups 48 patients each, Group (A) received the ERAS regimen and Group (B) was managed with the conventional care. Women with major medical or obstetric disorders were excluded.Results: Cases' age ranged between 18- 35 years without significant difference between groups. Also, gestational age, haemoglobin concentration and platelet count were comparable between groups. Intra and post-operative nausea and vomiting were significantly higher (p value <0.0366) in the control group (8 vs 17). Group A had significantly shorter interval to oral intake, ambulation, first intestinal sound and first motion. Moreover, the need to use opiate for pain control with overall pain scores were significantly lower in study group with significantly better satisfaction rates and shorter hospital stay.Conclusion: ERAS protocol for women planned for elective CS is effective in controlling perioperative gastrointestinal symptoms, pain control and encourages early ambulation with offering earlier resumption of intestinal motility, higher satisfaction and fewer days of admission.

The change in haemoglobin concentration between the first and third trimesters of pregnancy: a population study

BackgroundThe physiological fall in haemoglobin concentration from the 1st to the 3rd trimester of pregnancy is often quoted as 5 g/L. However, other studies have suggested varying levels of fall between 8 and 13 g/L. We evaluated the change in haemoglobin concentration between the 1st and 3rd trimesters of pregnancy in a multi-ethnic population of pregnant women.MethodsA retrospective cohort analysis of 7054 women with singleton pregnancies, giving birth during 2013–15 in a single urban maternity unit in England.We calculated the changes in haemoglobin concentration from 1st to 3rd trimester using the first trimester haemoglobin as the reference point. The population was stratified into sub-groups to explore any differences that existed within the population.ResultsIn general the fall in haemoglobin concentration was in the order of 14 g/L or 11% of the first trimester value. This fall was consistent for the majority of sub-groups of the population. The fall was lower (7.7%) in the most deprived section of the population, IMD1, but it increased to 11.7% when we restricted that sub-group to pregnant women without health problems during the index pregnancy. Conversely, there was an increase in haemoglobin of 10.2% in women whose first trimester haemoglobin concentration was in the lowest 5% of the total study population. The population fall in haemoglobin was 10.2 g/L (7.8%), after excluding cases above the 95th and below the 5th centiles, and women with a medical and/or obstetric disorder during the pregnancy.ConclusionThe fall in haemoglobin during pregnancy is in the order of 14 g/L or 11% of the first trimester level. This is 2 to 3 times higher than suggested by some guidelines and higher than previously published work. The results challenge the current accepted thresholds for practice, and have broader implications for diagnosis and managment of antenatal anaemia.Tweetable abstractFall in haemoglobin across pregnancy is around 14 g/L (11%) and significantly higher than previously stated in the pregnant population. This poses questions over currently accepted thresholds for anaemia in pregnancy.

Developmental origins of ovarian disorder: impact of maternal lean gestational diabetes on the offspring ovarian proteome in mice†.

Gestational diabetes mellitus (GDM) is an obstetric disorder affecting approximately 10% of pregnancies. The four high-fat, high-sucrose (HFHS) mouse model emulates GDM in lean women. Dams are fed a HFHS diet 1 week prior to mating and throughout gestation resulting in inadequate insulin response to glucose in mid-late pregnancy. The offspring of HFHS dams have increased adiposity, thus, we hypothesized that maternal metabolic alterations during lean GDM would compromise ovarian function in offspring both basally and in response to a control or HFHS diet in adulthood. Briefly, DLPL were lean dams and control diet pups; DLPH were lean dams and HFHS pups; DHPL were HFHS dams and control diet pups; and DHPH were HFHS dams and HFHS pups. A HFHS challenge in the absence of maternal GDM (DLPL vs. DLPH) increased 3 and decreased 30 ovarian proteins. Maternal GDM in the absence of a dietary stress (DLPL vs. DHPL) increased abundance of 4 proteins and decreased abundance of 85 proteins in the offspring ovary. Finally, 87 proteins increased, and 4 proteins decreased in offspring ovaries due to dietary challenge and exposure to maternal GDM in utero (DLPL vs. DHPH). Canopy FGF signaling regulator 2, deleted in azoospermia-associated protein 1, septin 7, and serine/arginine-rich splicing factor 2 were altered across multiple offspring groups. Together, these findings suggest a possible impact on fertility and oocyte quality in relation to GDM exposure in utero as well as in response to a western diet in later life.

Incidence and Risk Factors of Excess Gestational Weight Gain in Indian Women

&lt;p&gt;Excess Gestational Weight Gain (EGWG) increases risks of adverse obstetric outcomes, long-term obesity and metabolic disorders in mothers and children. The objective was to identify the incidence and risk factors of EGWG in the Indian context in order to develop effective preventative measures. A prospective cohort study was done to evaluate Gestational Weight Gain (GWG) in pregnant women who have completed a validated knowledge survey on GWG in 4 urban maternity tertiary centres and subsequently delivered at the same centres. Chi square test and Fisher’s exact test were used to identify risk factors associated with EGWG. 245 women completed the study. Gestational weight gain was classified as per the Institute of Medicine BMI-specific recommendations. Of the total women surveyed, 37.5% exceeded the GWG recommendation. The overweight and obese women constituted 50.2% of the entire population. In the overweight-obese category, 52% of women exceeded GWG recommendations. Risk factors for EGWG were high pre-pregnancy BMI (P&amp;lt;0.001), underestimation of pre-pregnancy weight category (P=0.003) and overestimation of GWG recommendations (P&amp;lt;0.001). In overweight-obese women, primiparity also increased risk of EGWG (P=0.04). Maternal age, education and perception of EGWG associated risks did not influence GWG. Ensuring women begin their pregnancies at a normal weight and provision of individualised GWG related counselling, either pre-conception or in the early stages of pregnancy may help foster appropriate weight gain in pregnancy. A modification in the current model of care involving detailed screening and nutritional counselling at the first visit itself could ensure effectiveness.&lt;/p&gt;

Enumeration of Fetal Red Blood Cells, Hemoglobin-Specific RBC Cells, and F Reticulocytes in Human Blood.

Recent advances in analytical cytometry have improved diagnostic tools for the study of erythropoiesis in anemic patients and resolution of differential diagnosis in diseases of the erythron. This article presents three applications of red blood cell (RBC) analysis-quantitation of fetal red cells, F-cell enumeration, and F-reticulocyte analysis-which improve diagnostic precision, sensitivity, and specificity, and provide better laboratory indicators of therapeutic efficacy in a variety of hematologic and obstetric disorders. Such advances also include the measurement and quantitation of RBC hemoglobins and their relative ribonucleic acid levels. These advances not only promise to improve diagnostic accuracy and laboratory precision over techniques such as the traditional manual reticulocyte counting method and the Kleihauer-Betke stain method for evaluating fetomaternal hemorrhage (FMH), but also serve as tools for newer assays of anemia diagnosis and improved clinical outcomes. In addition to the primary methods, supporting techniques for preparing spiked controls, automating data analysis, setting up a fetal hemoglobin acquisition protocol, and assaying reticulocytes using thiazole orange are also presented. © 2019 by John Wiley & Sons, Inc.

Insights of efferocytosis in normal and pathological pregnancy.

Efferocytosis, which is known as the phagocytic clearance of dying cells by professional as well as non-professional phagocytes, including a great number of intracellular/extracellular factors and signals, is interrelated with the immune system, contributing to local and systemic homeostasis, especially in tissues with high constitutive rates of apoptosis. Accumulating studies have indicated that immune dysregulation is associated with the pathogenesis of the female reproductive system, which causes preeclampsia (PE), recurrent spontaneous abortion (RSA), ruptured ectopic pregnancy, and so on. And some studies have revealed the pleiotropic and essential role of efferocytosis in these obstetrical disorders. More specifically, the occurrence and development of these diseases were in connection with some efferocytosis-related factors and signals, such as C1q, MBL, and IL-33/ST2. In this review, we systematically review the diverse impacts of efferocytosis in immune system and discuss its relevance to normal and pathological pregnancy. These findings may instruct future basic researches as well as clinical applications of efferocytosis-related factors and signals as latent predictors or therapeutic targets on the obstetrical disorders.

Endocervical trophoblast for interrogating the fetal genome and assessing pregnancy health at five weeks

Prenatal testing for fetal genetic traits and risk of obstetrical complications is essential for maternal-fetal healthcare. The migration of extravillous trophoblast (EVT) cells from the placenta into the reproductive tract and accumulation in the cervix offers an exciting avenue for prenatal testing and monitoring placental function. These cells are obtained with a cervical cytobrush, a routine relatively safe clinical procedure during pregnancy, according to published studies and our own observations. Trophoblast retrieval and isolation from the cervix (TRIC) obtains hundreds of fetal cells with >90% purity as early as five weeks of gestation. TRIC can provide DNA for fetal genotyping by targeted next-generation sequencing with single-nucleotide resolution. Previously, we found that known protein biomarkers are dysregulated in EVT cells obtained by TRIC in the first trimester from women who miscarry or later develop intrauterine growth restriction or preeclampsia. We have now optimized methods to stabilize RNA during TRIC for subsequent isolation and analysis of trophoblast gene expression. Here, we report transcriptomics analysis demonstrating that the expression profile of TRIC-isolated trophoblast cells was distinct from that of maternal cervical cells and included genes associated with the EVT phenotype and invasion. Because EVT cells are responsible for remodeling the maternal arteries and their failure is associated with pregnancy disorders, their molecular profiles could reflect maternal risk, as well as mechanisms underlying these disorders. The use of TRIC to analyze EVT genomes, transcriptomes and proteomes during ongoing pregnancies could provide new tools for anticipating and managing both fetal genetic and maternal obstetric disorders.

SFlt‐1 Splicing Regulation by U2AF65 and JMJD6 in Endothelial Cells

The obstetric disorder preeclampsia (PE) is a condition presenting with new onset hypertension and other co‐morbidities such as proteinuria and endothelial dysfunction. Women with preeclamptic pregnancies have significantly increased circulating levels of the soluble vascular endothelial growth factor (VEGF) receptor Flt‐1 (sFlt‐1). Acting as a VEGF antagonist, which is crucial for the growth and proliferation of endothelial cells, sFlt‐1 causes decreased bioavailability of VEGF. The mechanism regulating the alternative splicing of full length Flt‐1 to the soluble variant are not understood, though U2AF65 and JMJD6 are two proteins which have been implicated in splicing event. Previous research has suggested that U2AF65 promotes the splicing of sFlt‐1, while JMJD6 antagonizes splicing by marking U2AF65 for degradation. Using human umbilical vein endothelial cells (HUVECs), we tested the hypothesis that U2AF65 and JMJD6 were both necessary for alternative splicing in endothelial cells. siRNA was utilized to knock down both U2AF65 (1± 0.012 Fold vs 0.136± 0.017 Fold; p&lt;0.001) and JMJD6 (0.87±0.17 Fold vs 0.077 ± 0.019 Fold; p&lt;0.001) when normalized to β‐actin. Surprisingly, when we measured sFlt‐1 variants 2 and 3, the two most common variants in humans, we found no difference in sFlt‐1 expression. Additionally, we measured expression of the full length Flt‐1, and similarly saw no changes. Next, we overexpressed both U2AF65 and JMJD6 and assessed levels by qRT‐PCR. We observed a trend for ~2‐fold increase in U2AF65 200% (0.85 ± 0.20 Fold vs 1.899 ± 0.39 Fold; p=0.22) though this did not reach significance. Interestingly, in addition to significantly overexpressing JMJD6 (1.27 ± 0.27 Fold vs 2.40 ± 0.31 Fold; p&lt;0.01), cells overexpressing JMJD6 also had significantly higher expression of U2AF65 (0.85 ± 0.20 Fold vs 2.63 ± 0.30 Fold; p&lt;0.05). We measured expression of the FLT1 gene, with no changes seen in the expression of Flt‐1 or sFlt‐1 version 2. The sFlt‐1 variant 3, however, was significantly higher in cells overexpressing JMJD6 (1.008 ± 0.09 Fold vs 1.56 ± 0.14 Fold; p&lt;0.05). Despite the message levels remaining unchanged, sFlt‐1 protein was affected by U2AF65 and JMJD6, with strong trends toward decreased sFlt‐1 in with knock down of U2AF65 (5066 ± 644.3 pg/mL vs 3231 ± 193.5 pg/mL; p=0.067) and JMJD6 (5066 ± 644.3 pg/mL vs 3447 ± 605 pg/mL; p=0.09). Cells which had expression of both U2AF65 and JMJD6 knocked down exhibited an additive effect of sFlt‐1 protein decrease (5066 ± 644.3 pg/mL vs 2166 ± 63.6 pg/mL; p&lt;0.01). Similar, though non‐significant, trends of a positive correlation were seen in cells overexpressing U2AF65 and JMJD6 having slightly increased sFlt‐1 in the media. Because the message levels did not differ greatly among the transformed cells, we looked at heparanase (HPSE) expression as a modulator of sFlt‐1 release into the media. Though there was no change in HPSE expression in knockdown cells, significantly higher HPSE expression was seen in cells overexpressing both U2AF65 and JMJD6 (1.0 ± 0.03 Fold vs 1.97 ± 0.15 Fold; p&lt;0.001). These data suggest that U2AF65 and JMJD6 play an important role in the release of sFlt‐1, but may not be part of the alternative splicing machinery. Future experiments will look at other potential modulators regulating both sFlt‐1 and heparanase, such as MMP‐9.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Influence of salbutamol on the anticonvulsant potency of the antiepileptic drugs in the maximal electroshock-induced seizures in mice.

β2-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β2-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures. Seizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals' motor coordination and memory processes was also evaluated. Single SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β2-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals' motor performance and memory after both single and 7 days administration. Presented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β2-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.

Chromogranin A: its known and possible roles in obstetrics and gynecology.

Chromogranin A (CgA) is a prohormone initially extracted from the adrenal medulla, however, increased quantities of CgA are secreted by a wide array of human tissues in the course of a variety of disorders. This protein exhibits a number of interesting endocrine and non-endocrine functions. Here we briefly review the possible involvements of CgA in the areas covered by obstetrics and gynecology. Our account indicates the need to verify its association with the intrapartum fetal stress, and the involvement of CgA in the pathomechanisms of obstetric disorders related to placental dysfunction, as well as in the pathogenesis of endometrioid endometrial cancer as a hormonally regulated malignancy.