Alterations In Placenta Research Articles

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes

BackgroundIn recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.MethodsGiven the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).ResultsReduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.ConclusionBased on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Unique Ultrastructural Alterations in the Placenta Associated With Macrosomia Induced by Gestational Diabetes Mellitus

Abstract Objective To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)–induced macrosomia, term nondiabetic macrosomia, and normal pregnancies. Methods Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively. Results The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 vs. 3192.00 ± 328.70, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 vs. 3192.00 ± 328.70, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 vs. 490.00 ± 51.48, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 vs. 684.00 ± 62.69, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane. Conclusion Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.

Placenta with Pre-Eclampsia: A Systematic Review

The objective of this study was to carry out a systematic review that the amount of anatomopathological alterations in placentas from women who would develop PE would be higher compared to placentas from pregnant women without preeclampsia. In methods, for this systematic review, the keywords (“preeclampsia” and “placenta”) were used, four databases were searched: SciELO, Lilacs, Google Scholar and Embase. In the results obtained, it is observed that, of the Of the 86 registries identified, 6 were eligible. Other findings that, due to their frequency and maternal and fetal adverse outcomes, are very important: microscopic and macroscopic alterations, firstly, excess fibrin, secondly, abundant syncytial knots and, secondly, abundant syncytial knots. Thirdly, heart attacks. Within the macroscopic alterations of the placenta we found: low-weight placentas and finally, the evaluation of the methodological certainty of the six articles that entered the SR; they reached a score of >70%, classifying them as “sufficiently reported” articles. In conclusion, we say that the anatomopathological alterations that occur in the placenta lead to a dysfunctional, hypoxic and ischemic placenta, causing PE and maternal, fetal and neonatal complications.

Histological Alterations in Placentas of Pregnant Women with SARS-CoV-2 Infection: A Single-Center Case Series.

This study aimed to investigate the histopathological changes associated with SARS-CoV-2 infection in placentas. A case series of anatomopathological analysis was conducted on the placentas of pregnant women with SARS-CoV-2 who delivered between March and December 2020 at Santo Amaro Hospital (HSA) in Salvador, Brazil. Out of the 29 placentas examined, the median weight was 423.0 (IQR: 385.0-521.0) g. Among them, 58.3% (n = 14) had inadequate weight relative to the newborn's weight. The histopathological findings revealed that 86.2% (n = 25) of the placentas had poorly defined lobes, and the fetal and maternal surface color was normal in 89.7% (n = 26) and 93.1% (n = 27), respectively. Additionally, 51.7% (n = 15) of the umbilical cords displayed hypercoiling. The most frequent microscopic finding was infarction, present in 35.3% (n = 6) of the cases, followed by 11.8% (n = 2) for each of chorioamnionitis, chronic villitis, focal perivillositis, and laminar necrosis. Analysis of the umbilical cords identified 23.5% (n = 4) cases of intervillous thrombosis, while amnion analysis showed 13.8% (n = 4) cases of squamous metaplasia. Extraplacental membrane examination revealed fibrin deposition in 93.1% (n = 27) of the cases, necrosis in 62.0% (n = 18), calcifications in 51.7% (n = 15), cysts in 37.9% (n = 11), neutrophilic exudate in 17.2% (n = 5), thrombosis in 13.7% (n = 4), and delayed placental maturation in 6.9% (n = 2). All analyzed placentas exhibited histopathological changes, primarily vascular and inflammatory, which indicate SARS-CoV-2 infection in term pregnancies. These alterations could be associated with impaired placental function, fetal growth restriction, preeclampsia, and prematurity. However, further prospective studies are required to validate the type, prevalence, and prognosis of each of these changes.

Effects of Diabetes and Hypertension on Placenta

Placental insufficiency is the failure of the placenta to supply nutrients to the fetus and remove toxic wastes; it is a common cause of intra uterine growth restriction (IUGR), fetal distress peri and postnatal mortality. Specifically gestational diabetes and hypertension during pregnancy alters placental architecture which contributes to insufficiency of the placenta. Placenta is the most accurate record of infant’s prenatal experiences. Clinical condition such as hypertension and diabetes that complicate pregnancy leads to significant structural changes in placenta, these histological changes and morphological alterations in placenta lead to insufficiency, resulting in IUGR and fetal distress. In the present study morphology of placentas collected from diabetic and hypertensive pregnancy will be observed, the histo-pathological findings will be recorded and correlated to birth weight, APGAR scores and congenital anomalies of babies and will be compared to the findings in normal placentas also. This study will be beneficial for obstetrician and pediatrician in gathering knowledge about patho genesis of placental insufficiency; it will add to the knowledge on placental morphology and will high light the abnormalities in placental anatomy.

Immunohistopathological changes in the placenta of malaria-infected women in unstable transmission setting of Aligarh

IntroductionPregnant women are more susceptible to malaria due to a combination of physiological and immunological changes. The infection may even affect the growth and survival of the foetus, which mainly occur when parasite enters the placenta. The sequestration of infected erythrocytes may trigger the host response, leading to placental inflammation and altered development, affecting the structure and nutrient transport of placenta. These factors collectively impair placental functions and affect foetal growth. MethodsPregnant women with peripheral parasitaemia for P. falciparum and P. vivax (20 each) were included in the present study, along with 15 age-matched uninfected healthy pregnant women. Placentae were analysed for the presence of local parasitaemia along with pathological lesions caused due to the parasite. Immunohistochemical staining for CD20, CD45 and CD68 cells was performed for examining the specific leucocytes in the intervillous space of the placenta. ResultsOf the 20 individuals with P. falciparum, only seven placentae showed parasitaemia, whereas individuals with P. vivax showed no placental infection. The pathological changes observed in the P. falciparum-infected placenta include syncytial knotting, excess fibrinoid deposition, syncytiotrophoblast necrosis, syncytial rupture, thickening of trophoblast basement membrane and increased collagen deposition. Immunohistochemical staining showed a significant increase in B cells (CD20), leucocytes (CD45) and monocytes and macrophages (CD68) in the P. falciparum-infected placenta (p < 0.0001). DiscussionThe result implies that P. falciparum is responsible for pathological alterations in placenta, affecting the nutrient transport across placenta and foetal growth. The immune cells also migrate to the placenta and accumulate in the intervillous space to show humoral and cell-mediated immunity against the parasite.

Epigenetic Alterations Related to Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.

Effects of norfloxacin on fetal development in pregnant female rats

Objective: To evaluate the effect of norfloxacin on pregnant female rats. Animals: 30 pregnant female rats (170-200 gm of weight and 3.5-4 months age). Design: Randomized controlled study. Procedures: The effect of orally administrated norfloxacin, given twice daily for 10 successive days, on the fetal development in pregnant female rats at therapeutic (35 mg/kg) and double therapeutic (70 mg/kg) doses was investigated in pregnant female rats. At 6th -15th day of pregnancy, 30 females were classified, in groups of ten rats, into 3 groups.Group 1 (control group): rats were given distilled water orally. Group 2: rats were given norfloxacin at a dose rate of 35 mg/kg bwt. Group 3: rats were given norfloxacin at a double therapeutic dose of 70 mg/kg bwt. At 20th day of gestation all pregnant rats were anesthetized to determine the changes; if any; in fetal development (morphological, visceral, skeletal and histopathological examinations) and on treated dams (biochemical parameters of serum and histopathological alterations in placenta, liver and kidney). Results: Administration of norfloxacin, in both doses, to pregnant females decreased the number of viable feti, fetal body weight and crown-rump length, andincreased the number of resorbed feti (P< 0.05).It also induced visceral and skeletal abnormalities in feti. Histopathological examination of internal organs to both dams and feti revealed pathological alterations in liver and kidney of both, and placenta of the dam.Administration of norfloxacin at both therapeutic and double therapeutic doses increased maternal serum transferases levels (ALT and AST), decreased serum albumin and total portein levels, and increased serum levels of urea and creatinine (P< 0.05). Conclusion and clinical relevance: High doses of norfloxacin induce fetal defects and abnormalities in early stage of gestation in rats.

Chemotherapy for breast cancer during pregnancy induces vascular alterations and impaired development of placental villi: A preliminary histopathological study

ObjectiveTo evaluate histological alterations in placentas of women affected by breast cancer and treated with chemotherapy during pregnancy. Study designWe retrospectively reviewed histological slides of 23 placentas of patients affected by breast cancer and treated with chemotherapy during pregnancy and 23 control placentas of women without breast cancer and with physiological pregnancies of the same gestational age. ResultsAll the patients had breast ductal infiltrating carcinoma, 19 of 23 cases had a G3 cancer.All patients were treated with 2–6 cycles of chemotherapy starting after 16 weeks of gestation, with different protocols.No hypertensive complications and no pre-eclampsia episodes were observed; birth weight was consistent with gestational age in all babies in both group with no uneventful outcomes and no perinatal mortality or fetal malformations.Twenty out of 23 cases (86 %) showed hypoxia-induced villous alterations, including increased syncytial knotting (Tenney-Parker changes), perivillar fibrin deposits, distal villous hypoplasia or accelerated maturation and focal villous chorangiosis. These alterations were found in 19 out of 23 controls (83 %), with no statistically significant difference between the two groups. ConclusionsThese results shows that chemotherapy in the second and third trimester of pregnancy may lead to non-specific alterations in placental vasculature and morphology.

Impaired Mitochondrial Function Results from Oxidative Stress in the Full-Term Placenta of Sows with Excessive Back-Fat.

Simple SummaryPlacental dysfunction associated with maternal obesity has been demonstrated to be a possible detrimental determinant for a reproductive disorder in human and animals such as pigs. Moreover, there exists a substantial amount of evidence supporting that mitochondrial dysfunction associated with obesity contributes to dysfunction of highly metabolic tissues, including adipose, skeletal muscle and placenta. Despite previous reports have demonstrated that back-fat thickness of sows is associated with placental dysfunction, the influences of excessive back-fat on mitochondrial structure and function in porcine placenta still remain elusive. In this study, animal (Landrace) and cell in vitro model (pig placental trophoblasts) were employed to evaluate mitochondrial alterations in the placentas of sows with different back-fat depth. We revealed that excessive back-fat of sows is associated with placental mitochondrial abnormalities corresponding to decreased ATP production and impaired mitochondrial respiration in the placenta. Together, our findings develop the understanding about the impact of excessive back-fat induced oxidative stress on mitochondrial alterations in the pig placenta, which may contribute to generate some strategies in future to improve sow reproduction.The aim of this study was to determine the effect of excessive back-fat (BF) of sows on placental oxidative stress, ATP generation, mitochondrial alterations in content and structure, and mitochondrial function in isolated trophoblasts. Placental tissue was collected by vaginal delivery from BFI (15–20 mm, n = 10) and BFII (21–27 mm, n = 10) sows formed according to BF at mating. Our results demonstrated that excessive back-fat contributed to augmented oxidative stress in term placenta, as evidenced by excessive production of ROS, elevated protein carbonylation, and reduced SOD, GSH-PX, and CAT activities (p < 0.05). Indicative of mitochondrial dysfunction, reduced mitochondrial respiration in cultured trophoblasts was linked to decreased ATP generation, lower mitochondrial Complex I activity and reduced expression of electron transport chain subunits in placenta of BFII sows (p < 0.05). Meanwhile, we observed negative alterations in mitochondrial biogenesis and structure in the placenta from BFII group (p < 0.05). Finally, our in vitro studies showed lipid-induced ROS production resulted in mitochondrial alterations in trophoblasts, and these effects were blocked by antioxidant treatment. Together, these data reveal that excessive back-fat aggravates mitochondrial injury induced by increased oxidative stress in pig term placenta, which may have detrimental consequences on placental function and therefore impaired fetal growth and development.

Multigenerational and Transgenerational Effects of Dioxins.

Dioxins are ubiquitous and persistent environmental contaminants whose background levels are still reason for concern. There is mounting evidence from both epidemiological and experimental studies that paternal exposure to the most potent congener of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can lower the male/female ratio of offspring. Moreover, in laboratory rodents and zebrafish, TCDD exposure of parent animals has been reported to result in reduced reproductive performance along with other adverse effects in subsequent generations, foremost through the paternal but also via the maternal germline. These impacts have been accompanied by epigenetic alterations in placenta and/or sperm cells, including changes in methylation patterns of imprinted genes. Here, we review recent key studies in this field with an attempt to provide an up-to-date picture of the present state of knowledge to the reader. These studies provide biological plausibility for the potential of dioxin exposure at a critical time-window to induce epigenetic alterations across multiple generations and the significance of aryl hydrocarbon receptor (AHR) in mediating these effects. Currently available data do not allow to accurately estimate the human health implications of these findings, although epidemiological evidence on lowered male/female ratio suggests that this effect may take place at realistic human exposure levels.

Prenatal exposure to persistent organic pollutants and methylation of LINE-1 and imprinted genes in placenta: A CHECK cohort study

Prenatal exposure to persistent organic pollutants (POPs) has been linked to numerous adverse birth outcomes among newborn infants in many epidemiological studies. Although epigenetic modifications have been suggested as possible explanations for those associations, studies have rarely reported a relationship between POP exposure during pregnancy and DNA methylation in the placenta.In the present study, we investigated the association between prenatal exposure to several POPs, including organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs), and methylation levels of long interspersed element 1 (LINE-1), as well as imprinted genes in placental DNAs among Korean mother-child pairs (N = 109). We assessed the association of DNA methylation not only with each target POP (single-POP models) but also with multiple POPs applying principal component analysis (multiple-POP models). Potential associations between placental DNA methylation and birth outcomes of newborn infants were also estimated.In single-POP models, significant associations were detected between OCP measurements and placental DNA methylation. Elevated concentrations of β-hexachlorhexane (β-HCH) in maternal serum collected during delivery were significantly associated with a decrease in methylation of LINE-1 in the placenta. Higher levels of p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) in maternal serum were associated with hypermethylation of insulin-like growth factor 2 (IGF2). In multiple-POP models, a significant and positive association between DDTs and IGF2 methylation was also observed. Placental LINE-1 methylation was inversely associated with birth length. Our observations indicate that prenatal exposure to several POPs including DDTs is associated with the changes in methylation of genes, including major imprinted genes in the placenta. The consequences of these epigenetic alterations in placenta during development deserve further investigation.

Immunohistological Techniques.

Preeclampsia is associated with histological alterations in the placenta. These alterations can be described by means of histological techniques. More specifically, immunohistochemistry could be used to detect proteins, and these in turn may be used to identify a specific cell type, to differentiate it from other cell types and to detect the expression of some markers deregulated in preeclampsia.This chapter focuses on the detection of specific cellular and molecular markers that evidence the alterations in the human placenta in preeclampsia.

The alteration in placental volume and placental mean grey value in growth-restricted pregnancies assessed by 3D ultrasound

We aimed to evaluate the volumetric and echogenic alterations in placentas between the intrauterine growth restriction (IUGR) and normal pregnancies using three-dimensional ultrasound and virtual organ computer-aided analysis (VOCAL) software. This case–control prospective study consisted of 48 singleton pregnancies complicated by IUGR and 60 healthy singleton pregnancies matched for maternal age, gestational age and parity. Placental volume (PV) and placental volumetric mean grey values (MGV) were evaluated. PV (cm3) was analysed using the VOCAL imaging analysis program, and 3D histogram was used to calculate the volumetric MGV (%). PV was 278.50 ± 63.68 and 370.98 ± 97.82 cm3 in IUGR and control groups, respectively (p = 0.004). MGV of the placenta was 38.24 ± 8.41 and 38.24 ± 8.41 in IUGR and control groups, respectively (p = 0.30). receiver operator curve (ROC) curve analysis revealed that area under curve was 0.731 for PV. Correlation analysis revealed that PV was significantly associated with estimated fetal weight (r = 0.319, p = 0.003), biparietal diameter (r = 0.346, p = 0.002), head circumference (r = 0.269, p = 0.019), abdominal circumference (r = 0.344, p = 0.002) and femur length (r = 0.328, p = 0.004). PV was inversely related to the umbilical artery pulsatility index (r = − 0.244, p = 0.017). To the best of our knowledge, this is the first study evaluating volumetric MGV in IUGR placentas by comparing them with healthy pregnancies. Our study showed that PV diminishes significantly in IUGR pregnancies, whereas volumetric MGV does not alter significantly.

Cytotrophoblast alterations in placentas from disorders associated with anti-phospholipid antibodies

s / Placenta 35 (2014) A1eA23 A16 using the QIAamp® DNA FFPE Tissue Kit (Qiagen). Bisulfite treatment was followed by MSP. DNA was amplified using the Platinum® Blue (Invitrogen). The expression of Notch1 and Dll1 was detected by IHC using EnVision method. Results: The rates of Dll1 promoter hypermethylation were significantly higher in the early-onset PE group (61.5%; 8/13) than in late-onset PE group (12.0%; 3/25; P<0.001). In addition, their rates were significantly higher in the first trimester miscarriage group (80.0%, 8/10) than in the second trimester stillbirth (6.7%, 1/15; P<0.001). No significant differences in the rates of Notch1 promoter hypermethylation were found among the groups studied. Dll1 and Notch1 are expressed in the cytoplasm of villous trophoblast and decidual cell. In our preliminary study, those proteins expression are not associated with corresponding those methylation status. Conclusions: The epigenetic inactivation of Dll1 is involved in the occurrence of adverse outcome of pregnancy, especially early-onset PE. Dll1 promoter hypermethylation is expected to be a target of molecular diagnosis and treatment of these diseases. O-059. CYTOTROPHOBLAST ALTERATIONS IN PLACENTAS FROM DISORDERS ASSOCIATED WITH ANTI-PHOSPHOLIPID ANTIBODIES Rie Kawaguchi, Akiko Konoshi, Yukiko tanuma, Taizan Kamide, Hiroaki Aoki, Tomohiro Tanemoto, Kuniaki Oura, Aikou Okamot. Department of OB/GYN, Jikei Univ. School of Med., Japan Objectives: Pregnancy pathologies such as preeclampsia, fetal growth restriction and abruption are well known to be affected by an impaired placental development. Antiphospholipid antibodies (APLs) are associated with placental insufficiency by activation of the complement cascade. Here we investigated the effect of APLs and dysregulated clotting factors on the biology of villous trophoblast. Methods: Placentas were collected from a normal control group (NC; n1⁄48, 27-38 gestational weeks), an APL group (n1⁄410, 25-36 weeks), and a NAPS group (n1⁄410, 27-35 weeks), where patients had no APL, but disorders of serum clotting factors. Placentas were stained for anti Ki-67 and anticytokeratin 7 to selectively identify proliferating villous cytotrophoblasts. Images were systematically randomly selected and cytotrophoblasts counted. One way ANOVA and post hoc analysis were applied as statistical analysis. Results: The ratio of Ki-67 positive cytotrophoblasts in NC gradually decreased in accordance with gestational age, while this was not apparent in APS and NAPS. The mean of Ki-67 positive cells was significant reduced in APL (12.1 ±7.1%) and CF (13.3 ±5.8%) compared to NC (22.6 ±6.4%). The total number of cytotrophoblasts was reduced in APS (578 ±209) compared to NAPS (822 ±232) and NC (780 ±149). Conclusion: Throughout the third trimester of pregnancy there are significant differences in cytotrophoblast features such as total number and rate of proliferating cells in patients with APL and a dysregulated clotting system. Although cytotrophoblast proliferation was reduced in all compromised placentas, the total number of cytotrophoblasts only decreased in APS. We suggest that APL promote inhibition of cytotrophoblast proliferation throughout pregnancy, while in the NAPS group, an increasing amount of fibrin depositions finally leads to a decrease in trophoblast proliferation but does not affect total cell count. O-060. CLINICOPATHOLOGICAL ANALYSIS OF A PATIENT WITH CERVICOISTHMIC PREGNANCY: IMPLICATION OF PRECURSOR LESION TO PLACENTA ACCRETE Yosuke Sugita, Koichi Yoneyama, Mirei Yonezawa, Yuka Shirai, Kenichiro Watanabe, Nozomi Ouchi, Yoshimitsu Kuwabara, Toshiyuki Takeshita. Nippon Medical School Hospital Obstetrics &; Gynecology, Japan Cervico-isthmic pregnancy is rare and might be a part of the pathogenesis of placenta accreta. However, this entity of the disease is not widely known and there is no consensus on its management. Here we report a patient with cervico-isthmic pregnancy in a 34-year-old woman with the history of cesarean section delivery. The patient was referred to Nippon Medical School Hospital for suspicion of a cervical pregnancy. Transvaginal ultrasound revealed the gestational sac with the fetal heartbeat located in the cervico-isthmic region adjacent to the prior cesarean delivery scar. We clinically diagnosed it with a cesarean scar pregnancy, and total abdominal hysterectomy was performed. Macroscopically, the gestational sac attached to the posterior wall of the cervico-isthmic region. Histological examination revealed muscle infiltration of the intermediate trophoblast in the cervico-isthmic region. This is an important case showing the possibility of pathogenesis of placenta accreta through a cervico-isthmic pregnancy. O-063. A CASE OF INTRAPLACENTAL CHORIOCARCINOMA IDENTIFIED WHILE SEARCHING FOR THE CAUSE OF FETOMATERNAL HEMORRHAGE Misato Ogino , Kaori Kawakita , Nobuko Yamashita , Nobuyuki Tomura , Rie Sakai , Hitomi Okusugi , Eri Konda , Yumiko Sahara , Yasuhito Takeuchi , Misa Ishihara , Kimio Hashimoto . Department of Obstetrics and Gynecology, Nishikobe medical center, Japan; Department of Pathology, Nishikobe medical center,

Ethanol cytotoxic effect on trophoblast cells

Prenatal ethanol exposure may cause both, altered fetal neurodevelopment and impaired placental function. These disturbances can lead to growth retardation, which is one of the most prevalent features in Fetal Alcohol Syndrome (FAS). It is not known whether there is a specific pattern of cytotoxicity caused by ethanol that can be extrapolated to other cell types. The aim of this study was to determine the cytotoxic effects caused by sustained exposure of trophoblast cells to ethanol. The cytotoxic effect of sustained exposure to standard doses of ethanol on an in vitro human trophoblast cell line, JEG3, was examined. Viable cell count by exclusion method, total protein concentration, lactate dehydrogenase (LDH) activity and activation of apoptotic markers (P-H2AX, caspase-3 and PARP-1) were determined. Sustained exposure to ethanol decreased viable cell count and total protein concentration. LDH activity did not increased in exposed cells but apoptotic markers were detected. In addition, there was a dose-dependent relationship between ethanol concentration and apoptotic pathways activation. Sustained ethanol exposure causes cellular cytotoxicity by apoptotic pathways induction as a result of DNA damage. This apoptotic induction may partially explain the altered function of placental cells and the damage previously detected in other tissues.

Effect of maternal iron status on placenta, fetus and newborn

Maternal anemia (hypoferriemia) results in increased pre-term and low birth weight deliveries and higher rate of stillbirths. There are irreversible structural alterations in placenta. The transfer of iron to fetus is reduced in spite of gradient in relation to severity of maternal hypoferriemia. The fetal hepatic and brain iron contents were reduced. The brain iron reduction was irreversible on rehabilitation and was associated with irreversible neurotransmitter and their receptor alterations. Key words: Maternal anemia, stillbirths, placenta.

Exposure and fetal growth-associated miRNA alterations in the human placenta

Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures and fetal growth is providing critical insights into the biology of development, response to in utero exposure, and future disease risk assessment. This review aims to highlight previous studies describing changes in miRNA expression in the human placenta associated with in utero exposure and fetal growth and seeks to assess the future directions in this exciting field of research.

Toxicity of 3′3-ditrifluormethyldiphenyl diselenide administered during intra-uterine development of rats

The aim of this study was to assess the effects of the organoselenium compound, 3′3-ditrifluormethyldiphenyl diselenide [(F 3CPhSe) 2], during the intra-uterine development of Wistar rats. Dams were given repeated doses of 1, 5 or 10 mg/kg (F 3CPhSe) 2 by intragastric route on gestation days 6–15, and cesarean sections were performed on day 20 of pregnancy. The numbers of implantation sites, living and dead fetuses and resorptions were recorded. Fetuses were weighed and stained with Alizarin red S for skeletal evaluation. The placental morphology was also evaluated. In 1 mg/kg (F 3CPhSe) 2 group, neither maternal toxicity nor prenatal growth retardation was observed. Conversely, in 5 and 10 mg/kg groups, there was a decrease in maternal weight gain during pregnancy indicating that (F 3CPhSe) 2 was maternally toxic, without affecting fetuses weight and length. (F 3CPhSe) 2 caused some morphological alterations in placenta of 5 and 10 mg/kg-exposed dams. Results also showed that skeletal variations were produced by (F 3CPhSe) 2 only at doses (10 mg/kg) in which a marked embryolethality was found. We conclude that (F 3CPhSe) 2 was toxic to the dams and induced embryofeto-toxicity at doses equal to 10 mg/kg.

MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and Tumor Necrosis Factor-α Levels

OBJECTIVE—In pregestational diabetes, the placenta at term of gestation is characterized by various structural and functional changes. Whether similar alterations occur in the first trimester has remained elusive. Placental development requires proper trophoblast invasion and tissue remodeling, processes involving matrix metalloproteinases (MMPs) of which the membrane-anchored members (MT-MMPs) such as MT1-MMPs are key players. Here, we hypothesize a dysregulation of placental MT1-MMP in the first trimester of type 1 diabetic pregnancies induced by the diabetic environment. RESEARCH DESIGN AND METHODS—MT1-MMP protein was measured in first-trimester placentas of healthy (n = 13) and type 1 diabetic (n = 13) women. To identify potential regulators, first-trimester trophoblasts were cultured under hyperglycemia and various insulin, IGF-I, IGF-II, and tumor necrosis factor-α (TNF-α) concentrations in presence or absence of signaling pathway inhibitors. RESULTS—MT1-MMP was strongly expressed in first-trimester trophoblasts. In type 1 diabetes, placental pro–MT1-MMP was upregulated, whereas active MT1-MMP expression was only increased in late first trimester. In isolated primary trophoblasts, insulin, IGF-I, IGF-II, and TNF-α upregulated MT1-MMP expression, whereas glucose had no effect. The insulin effect was dependent on phosphatidylinositol 3-kinase, the IGF-I effect on mitogen-activated protein kinase, and the IGF-II effect on both. CONCLUSIONS—This is the first study reporting alterations in the first-trimester placenta in type 1 diabetes. The upregulated MT1-MMP expression in type 1 diabetes may be the result of higher maternal insulin and TNF-α levels. We speculate that the elevated MT1-MMP will affect placental development and may thus contribute to long-term structural alterations in the placenta in pregestational diabetes.