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Pathologica Apr 2023Placental site trophoblastic tumor (PSTT), also known as atypical choriocarcinoma, syncytioma, chorioepitheliosis or trophoblastic pseudotumor, is a rare gestational... (Review)
Review
Placental site trophoblastic tumor (PSTT), also known as atypical choriocarcinoma, syncytioma, chorioepitheliosis or trophoblastic pseudotumor, is a rare gestational trophoblastic disease (0.25-5% of all trophoblastic tumors) and it is composed by neoplastic proliferation of intermediate trophoblasts at placental implantation site. It consists of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells with a characteristic vascular and myometrial invasion. Main differential diagnoses are gestational choriocarcinoma (GC) and epitelioid trophoblastic tumor (ETT). We present a case of PSTT in a 25-year-old woman. Neoplastic cells showed moderate/high nuclear pleomorphism, abundant amphophilic, eosinophilic and clear cytoplasm, numerous mitotic figures (10 mitoses/10 HPF), and myometrial invasion. Other features are necrosis, vascular invasion with replacement of myometrial vessels by tumor cells and hemorrhage. The patient showed typical low serum β-hCG levels and high serum humane placental lactogen (hPL) levels.
Topics: Female; Humans; Pregnancy; Adult; Trophoblastic Tumor, Placental Site; Placenta; Chorionic Gonadotropin; Uterine Neoplasms; Trophoblastic Neoplasms; Choriocarcinoma
PubMed: 37114629
DOI: 10.32074/1591-951X-873 -
BMJ Open Feb 2022Maternal metabolic disease states (such as gestational and pregestational diabetes and maternal obesity) are reaching epidemic proportions worldwide and are associated...
INTRODUCTION
Maternal metabolic disease states (such as gestational and pregestational diabetes and maternal obesity) are reaching epidemic proportions worldwide and are associated with adverse maternal and fetal outcomes. Despite this, their aetiology remains incompletely understood. Lactogenic hormones, namely, human placental lactogen (hPL) and prolactin (PRL), play often overlooked roles in maternal metabolism and glucose homeostasis during pregnancy and (in the case of PRL) postpartum, and have clinical potential from a diagnostic and therapeutic perspective. This paper presents a protocol for a systematic review which will synthesise the available scientific evidence linking these two hormones to maternal and fetal metabolic conditions/outcomes.
METHODS AND ANALYSIS
MEDLINE (via OVID), CINAHL and Embase will be systematically searched for all original observational and interventional research articles, published prior to 8 July 2021, linking hPL and/or PRL levels (in pregnancy and/or up to 12 months postpartum) to key maternal metabolic conditions/outcomes (including pre-existing and gestational diabetes, markers of glucose/insulin metabolism, postpartum glucose status, weight change, obesity and polycystic ovary syndrome). Relevant fetal outcomes (birth weight and placental mass, macrosomia and growth restriction) will also be included. Two reviewers will assess articles for eligibility according to prespecified selection criteria, followed by full-text review, quality appraisal and data extraction. Where possible, meta-analysis will be performed; otherwise, a narrative synthesis of findings will be presented.
ETHICS AND DISSEMINATION
Formal ethical approval is not required as no primary data will be collected. The results will be published in a peer-reviewed journal and presented at conference meetings, and will be used to inform future research directions.
PROSPERO REGISTRATION NUMBER
CRD42021262771.
Topics: Diabetes, Gestational; Female; Glucose; Humans; Meta-Analysis as Topic; Placenta; Postpartum Period; Pregnancy; Prolactin
PubMed: 35190436
DOI: 10.1136/bmjopen-2021-055257 -
Scientific Reports Nov 2019Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however...
Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however the intrauterine mechanisms involved remain unknown. This study in the rat assessed the impact of advanced maternal age on placental phenotype in relation to the growth of female and male fetuses. We show that relative to young (3-4 months) dams, advanced maternal age (9.5-10 months) compromises growth of both female and male fetuses but affects the placental phenotype sex-specifically. In placentas from aged versus young dams, the size of the placental transport and endocrine zones were increased and expression of Igf2 (+41%) and placental lactogen (Prl3b1: +59%) genes were upregulated in female, but not male fetuses. Placental abundance of IGF2 protein also decreased in the placenta of males only (-95%). Moreover, in placentas from aged versus young dams, glucocorticoid metabolism (11β-hsd2: +63% and 11β-hsd1: -33%) was higher in females, but lower in males (11β-hsd2: -50% and 11β-hsd1: unaltered). There was however, no change in the placental abundance of 11β-HSD2 protein in aged versus young dams regardless of fetal sex. Levels of oxidative stress in the placenta were increased in female and male fetuses (+57% and +90%, respectively) and apoptosis increased specifically in the placenta of males from aged rat dams (+700%). Thus, advanced maternal age alters placental phenotype in a sex-specific fashion. These sexually-divergent changes may play a role in determining health outcomes of female and male offspring of aged mothers.
Topics: Animals; Female; Fetal Development; Fetal Growth Retardation; Male; Maternal Age; Phenotype; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Factors
PubMed: 31780670
DOI: 10.1038/s41598-019-53199-x -
Diabetes Jan 2021Hypoadiponectinemia is a risk factor of gestational diabetes mellitus (GDM). Our previous study reported that adiponectin gene knockout mice ( ) develop GDM due to...
Hypoadiponectinemia is a risk factor of gestational diabetes mellitus (GDM). Our previous study reported that adiponectin gene knockout mice ( ) develop GDM due to insulin insufficiency. The main objective of this study was to elucidate the underlying mechanism through which adiponectin controls islet expansion during pregnancy. A significant reduction in β-cell proliferation rates, β-cell areas, and blood insulin concentrations was detected in mice at midpregnancy. Surprisingly, conditionally knocking down adiponectin receptor 1 () or genes in β-cells during pregnancy did not reduce β-cell proliferation rates or blood insulin concentrations. In vitro adiponectin treatment also failed to show any effect on β-cell proliferation of isolated pancreatic islets. It was reported that placental lactogen (PL) plays a crucial role in pregnancy-induced maternal β-cell proliferation. A significant decrease in phosphorylation of signal transducer and activator of transcription 5, a downstream molecule of PL signaling, was observed in islets from dams. The mRNA levels of mouse PL genes were robustly decreased in the placentas of dams. In contrast, adiponectin treatment increased PL expression in human placenta explants and JEG3 trophoblast cells. Most importantly, bovine PL injection restored β-cell proliferation and blood insulin concentrations in dams. Together, these results demonstrate that adiponectin plays a vital role in pregnancy-induced β-cell proliferation by promoting PL expression in trophoblast cells.
Topics: Adiponectin; Animals; Cell Line; Cell Proliferation; Female; Humans; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Mice; Mice, Knockout; Placenta; Placental Lactogen; Pregnancy; Receptors, Adiponectin; Trophoblasts
PubMed: 33087456
DOI: 10.2337/db20-0471 -
The Journal of Endocrinology Dec 2020Chorionic somatomammotropin (CSH) is a placenta-specific hormone associated with fetal growth, and fetal and maternal metabolism in both humans and sheep. We...
Chorionic somatomammotropin (CSH) is a placenta-specific hormone associated with fetal growth, and fetal and maternal metabolism in both humans and sheep. We hypothesized that CSH deficiency could impact sheep fetal liver glucose utilization. To generate CSH-deficient pregnancies, day 9 hatched blastocysts were infected with lentiviral particles expressing CSH-specific shRNA (RNAi) or scramble control shRNA (SC) and transferred to synchronized recipients. CSH RNAi generated two distinct phenotypes at 135 days of gestational age (dGA); pregnancies with IUGR (RNAi-IUGR) or with normal fetal weight (RNAi-NW). Fetal body, fetal liver and placental weights were reduced (P < 0.05) only in RNAi-IUGR pregnancies compared to SC. Umbilical artery plasma insulin and insulin-like growth factor 1 (IGF1) concentrations were decreased, whereas insulin receptor beta (INSR) concentration in fetal liver was increased (P < 0.05) in both RNAi phenotypes. The mRNA concentrations of IGF1, IGF2, IGF binding protein 2 (IGFBP2) and IGFBP3 were decreased (P < 0.05) in fetal livers from both RNAi phenotypes. Fetal liver glycogen concentration and glycogen synthase 1 (GYS1) concentration were increased (P < 0.05), whereas fetal liver phosphorylated-GYS (inactive GYS) concentration was reduced (P < 0.05) in both RNAi phenotypes. Lactate dehydrogenase B (LDHB) concentration was increased (P < 0.05) and IGF2 concentration was decreased (P < 0.05) in RNAi-IUGR fetal livers only. Our findings suggest that fetal liver glucose utilization is impacted by CSH RNAi, independent of IUGR, and is likely tied to enhanced fetal liver insulin sensitivity in both RNAi phenotypes. Determining the physiological ramifications of both phenotypes, may help to differentiate direct effect of CSH deficiency or its indirect effect through IUGR.
Topics: Animals; Female; Fetal Growth Retardation; Glucose; Glycogen; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Liver; Placental Lactogen; Pregnancy; RNA Interference; Sheep
PubMed: 33108344
DOI: 10.1530/JOE-20-0375 -
MAbs 2023Prolactin (PRL) has recently been demonstrated to elicit female-selective nociceptor sensitization and increase pain-like behaviors in female animals. Here we report the...
Prolactin (PRL) has recently been demonstrated to elicit female-selective nociceptor sensitization and increase pain-like behaviors in female animals. Here we report the discovery and characterization of first-in-class, humanized PRL neutralizing monoclonal antibodies (PRL mAbs). We obtained two potent and selective PRL mAbs, PL 200,031 and PL 200,039. PL 200,031 was engineered as human IgG1 whereas PL 200,039 was reformatted as human IgG4. Both mAbs have sub-nanomolar affinity for human PRL (hPRL) and produce concentration-dependent and complete inhibition of hPRL signaling at the hPRL receptor (hPRLR). These two PRL mAbs are selective for hPRL as they do not inhibit other hPRLR agonists such as human growth hormone or placental lactogen. They also cross-react with non-human primate PRL but not with rodent PRL. Further, both mAbs show long clearance half-lives after intravenous administration in FcRn-humanized mice. Consistent with their isotypes, these mAbs only differ in binding affinities to Fcγ receptors, as expected by design. Finally, PL 200,019, the murine parental mAb of PL 200,031 and PL 200,039, fully blocked stress-induced and PRL-dependent pain behaviors in female PRL-humanized mice, thereby providing preclinical proof-of-efficacy for PRL mAbs in mechanisms relevant to pain in females.
Topics: Female; Mice; Animals; Pregnancy; Prolactin; Receptors, Prolactin; Antibodies, Monoclonal; Placenta; Protein Binding
PubMed: 37698877
DOI: 10.1080/19420862.2023.2254676 -
Endocrine Journal May 2024The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A...
The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A report from 1984 examined the secretion pattern of PRL3B1 in prepartum mice. In the current study, we found contradictory findings in the secretion pattern that invalidate the previous report. By measuring maternal plasma PRL3B1 and PRL every 4 hrs from gestational day 17 (G17), we newly discovered that maternal plasma PRL3B1 levels decrease rapidly in prepartum C57BL/6 mice. Interestingly, the onset of this decline coincided with the PRL surge at G18, demonstrating a plasma prolactin axis shift from placental to pituitary origin. We also found that maternal plasma progesterone regression precedes the onset of the PRL shift. The level of Prl3b1 mRNA was determined by RT-qPCR in the placenta and remained stable until parturition, implying that PRL3B1 peptide production or secretion was suppressed. We hypothesized that production of the PRL family, the 25 paralogous PRL proteins exclusively expressed in mice placenta, would decrease alongside PRL3B1 during this period. To investigate this hypothesis and to seek proteomic changes, we performed a shotgun proteome analysis of the placental tissue using data-independent acquisition mass spectrometry (DIA-MS). Up to 5,891 proteins were identified, including 17 PRL family members. Relative quantitative analysis between embryonic day 17 (E17) and E18 placentas showed no significant difference in the expression of PRL3B1 and most PRL family members except PRL7C1. These results suggest that PRL3B1 secretion from the placenta is suppressed at G18 (E18).
PubMed: 38749736
DOI: 10.1507/endocrj.EJ23-0724 -
Animal Reproduction 2021The chemotaxis of subsp. and subsp. was determined in the presence of bovine cervical mucus and bovine placental extract. Some reported substances and ion in those...
The chemotaxis of subsp. and subsp. was determined in the presence of bovine cervical mucus and bovine placental extract. Some reported substances and ion in those materials, such amino acids, ferrous iron, hormones, sugars and organic acids were also investigated. Bovine cervical mucus, bovine placenta extracts and some substances and ion of these materials namely L-fucose, L- aspartate, L-glutamate, L-serine, ferrous iron, fumarate, pyruvate and succinate were chemoattractants. The chemottraction was significantly larger in higher concentrations of the tested substances and ion and significant differences among tested strains were also observed. Meso-erythritol and hormones bovine placental lactogen, 17β-estradiol, and progesterone did not elicit chemotactical response. In conclusion, this chemotactic behavior may guide the navigation in the bovine host's genital tract and be an important cofactor of tissue tropism for this bacterium.
PubMed: 34394754
DOI: 10.1590/1984-3143-AR2021-0008 -
Journal of Diabetes and Metabolic... Dec 2023Gestational diabetes mellitus (GDM) is a pathological condition in which the placenta releases a hormone called human placental lactogen that prevents maternal insulin... (Review)
Review
UNLABELLED
Gestational diabetes mellitus (GDM) is a pathological condition in which the placenta releases a hormone called human placental lactogen that prevents maternal insulin uptake. GDM is characterised by varying degrees of carbohydrate intolerance and is first identified during pregnancy. Around 5-17% of pregnancies are GDM pregnancies. Older or obese women have a higher risk of developing GDM during gestation. Hyperglycemia is a classic manifestation of GDM and leads to alterations in eNOS and iNOS expression and subsequently causes ROS and RNS overproduction. ROS and RNS play an important role in maintaining normal physiology, when present in low concentrations. Increased concentrations of ROS is harmful and can cause cellular and tissue damage. Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant molecules that manifests due to hyperglycemia. miRNAs are short, non-coding RNAs that play a critical role in regulating gene expression. Studies have shown that the placenta expresses more than 500 miRNAs, which play a crucial role in trophoblast division, movement, and apoptosis. Latest research has revealed that hyperglycemic conditions and increased oxidative stress, characteristic of GDM, can lead to the dysregulation of miRNAs. The placenta also releases miRNAs into the maternal circulation. The secreted miRNAs are encapsulated in exosomes or vesicles. These exosomes interact with tissues and organs at distant sites, releasing their cargo intracellularly. This crosstalk between hyperglycemia, ROS and miRNA expression in GDM has detrimental effects on both foetal and maternal health. One of the complications of GDM is preterm labour. GDM induced iNOS expression has been implicated in cervical ripening, which in turn causes preterm birth. This article focuses on the speculations of oxidative and nitrative stress markers that lead to detrimental effects in GDM. We have also envisaged the role of non-coding miRNA interactions in regulating gene expression for oxidative damage.
GRAPHICAL ABSTRACT
. I)(A) Placenta as a metabolic organ that provides the foetus with nutrients, oxygen and hormones to maintain pregnancy. Human placental lactogen (hPL) is one such hormone that is released into maternal circulation. hPL is known to induce insulin resistance. (B) ß-cell dysfunction leads to reduced glucose sensing and insulin production. Insulin resistance, a characteristic of GDM, exacerbates insulin ß cell dysfunction leading to maternal hyperglycemia. Hyperglycemia leads to increased ROS and RNS production through several mechanisms. Consequently, GDM is characterised by increased oxidative and nitrative stress.II)Exposure to maternal hyperglycemia causes increased ROS and RNS production in trophoblast cells. Oxidative stress caused by hyperglycemia may lead to eNOS uncoupling, causing eNOS to behave as a superoxide producing enzyme. iNOS expression in trophoblast cells leads to increased NO production. iNOS-derived NO reacts with ROS to produce RNS, thereby increasing nitrosative stress. Expression of antioxidant defences are reduced. Hyperglycemia and oxidative stress may alter the expression of some miRNAs. Some miRNAs are upregulated while others are downregulated. Some miRNAs are secreted into maternal circulation in the form of exosomes. Oxidative stress markers, nitrative stress markers and circulating miRNAs are found to be increased in maternal circulation.
PubMed: 37975145
DOI: 10.1007/s40200-023-01232-2 -
Cureus May 2023Mature cystic teratoma (MCT) is a benign germ cell tumor, histologically comprising components derived from mesoderm, ectoderm, and endoderm layer tissue. MCT usually...
Mature cystic teratoma (MCT) is a benign germ cell tumor, histologically comprising components derived from mesoderm, ectoderm, and endoderm layer tissue. MCT usually has foci of intestinal components and colonic epithelia. Pituitary teratomas containing complete colon features are very rare. Here, we present three cases of sellar teratoma in two men aged 50 and 65 years and a woman aged 30 years. All patients presented with asthenia, adynamia, and loss of strength. A pituitary mass was incidentally observed on magnetic resonance imaging. Histological features showed a mature teratoma formed by gut and colonic epithelium, extended lymphoid tissue with the formation of Peyer's patches, and muscular layer vestiges with a fibrous capsule. The immunohistochemical panel showed reactivity to cytokeratin (CK)7, CKAE6/AE7, carcinoembryonic antigen, octamer-binding transcription factor 4, cluster of differentiation (CD)20, CD3, vimentin, muscle actin, and in isolated cells. However, alpha-fetoprotein, beta-human chorionic gonadotropin, human placental lactogen, CK20, tumor suppressor protein 53, and Kirsten rat sarcoma were negative. This article describes the clinical and histological features of rare sellar masses as well as survival after therapy.
PubMed: 37292527
DOI: 10.7759/cureus.38729