Thyroid hormones (THs) regulate a number of metabolic processes during pregnancy. After implantation, the placenta forms and enhances embryonic growth and development. Dysregulated maternal THs ...signaling has been observed in malplacentation-mediated pregnancy complications such as preeclampsia, miscarriage, and intrauterine growth restriction (IUGR), but the molecular mechanisms involved in this association have not been fully characterized. In this review, we have discussed THs signaling and its roles in trophoblast proliferation, trophoblast differentiation, trophoblast invasion of the decidua, and decidual angiogenesis. We have also explored the relationship between specific pregnancy complications and placental THs transporters, deiodinases, and THs receptors. In addition, we have examined the effects of specific endocrine disruptors on placental THs signaling. The available evidence indicates that THs signaling is involved in the formation and functioning of the placenta and serves as the basis for understanding the pathogenesis and pathophysiology of dysthyroidism-associated pregnancy complications such as preeclampsia, miscarriage, and IUGR. Summary sentence Normal THs signaling promotes placentation; while abnormal THs signaling leads to malplacentation and its associated pregnancy complications, such as preeclampsia, miscarriage and IUGR.
The impact of bisphenol A on the placenta Adu-Gyamfi, Enoch Appiah; Rosenfeld, Cheryl S.; Tuteja, Geetu
Biology of reproduction,
05/2022, Volume:
106, Issue:
5
Journal Article
Peer reviewed
Open access
Bisphenol A (BPA), an endocrine-disrupting chemical, is used to produce a wide variety of plastic and common house-hold items. Therefore, there is potential continual exposure to this compound. BPA ...exposure has been linked to certain placenta-associated obstetric complications such as preeclampsia, fetal growth restriction, miscarriage, and preterm birth. However, how BPA exposure results in these disorders remains uncertain. Hence, we have herein summarized the reported impacts of BPA on the morphology and metabolic state of the placenta and have proposed mechanisms by which BPA affects placentation, potentially leading to obstetric complications. Current findings suggest that BPA induces pathological changes in the placenta and disrupts its metabolic activities. Based on exposure concentrations, BPA can elicit apoptotic or anti-apoptotic signals in the trophoblasts, and can exaggerate trophoblast fusion while inhibiting trophoblast migration and invasion to affect pregnancy. Accordingly, the usage of BPA products by pregnant women should be minimized and less harmful alternative chemicals should be explored and employed where possible. Summary Sentence This review provides insight into the mechanisms by which bisphenol A, an endocrine-disrupting chemical that is used in plastic found in common household items, affects placental development, potentially leading to pregnancy complications. Graphical Abstract
During pregnancy, there is increased expression of some cytokines at the fetal–maternal interface; and the clarification of their roles in trophoblast–endometrium interactions is crucial to ...understanding the mechanism of placentation. This review addresses the up-to-date reported mechanisms by which the members of the transforming growth factor beta superfamily regulate trophoblast proliferation, differentiation, and invasion of the decidua, which are the main phases of placentation. The available information shows that these cytokines regulate placentation in somehow a synergistic and an antagonistic manner; and that dysregulation of their levels can lead to aberrant placentation. Nevertheless, prospective studies are needed to reconcile some conflicting reports; and identify some unknown mediators involved in the actions of these cytokines before their detailed mechanistic regulation of human placentation could be fully characterized. Summary sentence The TGF beta superfamily are expressed in the placenta, and regulate the process of placentation through the activation of several signaling pathways.
As the first long noncoding RNA to be discovered, H19 has gained substantial attention as a key regulator of several biological processes and its roles in female reproductive biology are gradually ...getting revealed. Herein, we have summarized the current evidence regarding H19 expression pattern and involvement in the developmental and pathological processes associated with the ovary and the placenta. The findings indicate that within the ovaries, H19 is expressed in the antral and cystic atretic follicles as well as in the corpora lutea but absent in the primordial, primary, and secondary follicles. Its normal expression promotes the maturation of antral follicles and prevents their premature selection for the ovulatory journey while its aberrant induction promotes polycystic ovary syndrome development and ovarian cancer metastasis. In the placenta, H19 is highly expressed in the cytotrophoblasts and extravillous trophoblasts but weakly expressed in the syncytiotrophoblast layer and potentially controls trophoblast cell fate decisions during placenta development. Abnormal expression of H19 is observed in the placental villi of pregnancies affected by pre‐eclampsia and fetal growth restriction. Therefore, dysregulated H19 is a candidate biomarker and therapeutic target for the mitigation of ovarian and placenta‐associated diseases.
Significance statement
We have proposed mechanisms by which H19 facilitates antral follicle maturation and placenta development as well as how H19 upregulation promotes epithelial ovarian cancer metastasis. We hope that therapeutic inhibition of this mechanism in the ovarian microenvironment can help mitigate epithelial ovarian cancers in both drug‐resistant and nondrug resistant patients. We have proposed serum H19 level as a potential biomarker for the clinical assessment of ovarian reserve. The future research directions and the ideal experimental approaches we have highlighted will help discover more reliable information about H19 actions in the female reproductive system.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Decidualization is a crucial precedent to embryo implantation, as its impairment is a major contributor to female infertility and pregnancy complications. Unraveling the molecular mechanisms involved ...in the impairment of decidualization has been a subject of interest in the field of reproductive medicine. Evidence from several experimental settings show that exposure to bisphenol A (BPA), an endocrine‐disrupting chemical, affects the expression of several molecules that are involved in decidualization. Both low and high doses of BPA impair decidualization through the dysregulation of estrogen (ER) and progesterone (PR) receptors. Exposure to low doses of BPA leads to decreased levels and activities of several antioxidant enzymes, increased activity of endothelial nitric oxide synthase (eNOS), and increased production of nitric oxide (NO) via the upregulation of ER and PR. Consequently, oxidative stress is induced and decidualization becomes impaired. On the other hand, exposure to high doses of BPA downregulates ER and PR and impairs decidualization through two distinct pathways. One is through the upregulation of early growth response‐1 (EGR1) via increased phosphorylation of extracellular signal‐regulated protein kinases 1 and 2; and the other is through a reduced serum glucocorticoid‐induced kinase‐1 (SGK1)‐mediated downregulation of epithelial sodium channel‐α and the induction of oxidative stress. Thus, regardless of the dose, BPA can impair decidualization to trigger infertility and pregnancy complications. This warrants the need to adopt lifestyles that will decrease the tendency of getting exposed to BPA.
Exposure to both low and high doses of bisphenol A during pregnancy affects decidualization through interfering with estrogen and progesterone receptors. Both doses can induce oxidative stress to impair decidualization. High doses impair through the upregulation of early growth response‐1 and downregulation of epithelial sodium channel‐α.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The placenta serves as an essential organ for fetal growth throughout pregnancy. Histone modification is a crucial regulatory mechanism involved in numerous biological processes and development. ...Nevertheless, there remains a significant gap in our understanding regarding the epigenetic regulations that influence trophoblast lineage differentiation, a fundamental aspect of placental development. Here, through comprehensive mapping of H3K4me3, H3K27me3, H3K9me3, and H3K27ac loci during the differentiation of trophoblast stem cells (TSCs) into syncytiotrophoblasts (STs) and extravillous trophoblasts (EVTs), we reveal dynamic reconfiguration in H3K4me3 and H3K27ac patterns that establish an epigenetic landscape conducive to proper trophoblast lineage differentiation. We observe that broad H3K4me3 domains are associated with trophoblast lineage-specific gene expression. Unlike embryonic stem cells, TSCs lack robust bivalent domains. Notably, the repression of ST- and EVT-active genes in TSCs is primarily attributed to the weak H3K4me3 signal rather than bivalent domains. We also unveil the inactivation of TSC enhancers precedes the activation of ST enhancers during ST formation. Our results provide a comprehensive global map of diverse histone modifications, elucidating the dynamic histone modifications during trophoblast lineage differentiation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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The role of adiponectin in placentation and preeclampsia Adu‐Gyamfi, Enoch Appiah; Fondjo, Linda Ahenkorah; Owiredu, William K.B.A. ...
Cell biochemistry and function,
January 2020, 2020-Jan, 2020-01-00, 20200101, Volume:
38, Issue:
1
Journal Article
Peer reviewed
Preeclampsia is not fully understood; and few biomarkers, therapeutic targets, and therapeutic agents for its management have been identified. Original investigative findings suggest that abnormal ...placentation triggers preeclampsia and leads to hypertension, proteinuria, endothelial dysfunction, and inflammation, which are characteristics of the disease. Because of the regulatory roles that it plays in several metabolic processes, adiponectin has become a cytokine of interest in metabolic medicine. In this review, we have discussed the role of adiponectin in trophoblast proliferation, trophoblast differentiation, trophoblast invasion of the decidua, and decidual angiogenesis, which are the major phases of placentation. Also, we have highlighted the physiological profile of adiponectin in the course of normal pregnancy. Moreover, we have discussed the involvement of adiponectin in hypertension, endothelial dysfunction, inflammation, and proteinuria. Furthermore, we have summarized the reported relationship between the maternal serum adiponectin level and preeclampsia. The available evidence indicates that adiponectin level physiologically falls as pregnancy advances, regulates placentation, and exhibits protective effects against the symptoms of preeclampsia and that while hyperadiponectinemia is evident in normal‐weight preeclamptic women, hypoadiponectinemia is evident in overweight and obese preeclamptic women. Therefore, the clinical use of adiponectin as a biomarker, therapeutic target, or therapeutic agent against the disease looks promising and should be considered.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1, on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary ...syndrome. We generated a polycystic ovary syndrome mouse model by using dehydroepiandrosterone plus high-fat diet. Glycyrrhizin (100 mg/kg) was intraperitoneally injected into the polycystic ovary syndrome mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism, and some molecular mechanisms were investigated. Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance, and decreased insulin sensitivity in the polycystic ovary syndrome mice were reverted by glycyrrhizin. The increased high mobility group box 1 levels in the serum and ovarian tissues of the polycystic ovary syndrome mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor 9, myeloid differentiation factor 88, and nuclear factor kappa B as well as reduced expressions of insulin receptor, phosphorylated protein kinase B, and glucose transporter type 4 were restored by glycyrrhizin in the polycystic ovary syndrome mice. Glycyrrhizin could suppress the polycystic ovary syndrome-induced upregulation of high mobility group box 1, several inflammatory marker genes, and the toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B pathways, while inhibiting the insulin receptor/phosphorylated protein kinase B/glucose transporter type 4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against polycystic ovary syndrome. Summary Sentence Glycyrrhizin could improve inflammation, glucose metabolic disorders, and ovarian dysfunction in polycystic ovary syndrome mice by inhibiting the expression of high mobility group box 1.
Preeclampsia (PE) can occur antepartum or postpartum. When it develops de novo after childbirth, it is termed new-onset postpartum PE (NOPPE). Often, antepartum PE disappears after childbirth; ...however, in some women it persists after childbirth. This form of PE is termed persistent PE (PPE). Thus, there are two forms of postpartum PE: NOPPE and PPE. The pathogenesis and pathophysiology of these diseases have not been fully characterized, and whether NOPPE and PPE are different or similar pathological conditions remains unexplored. Thus, we aimed to compare the haematological and biochemical characteristics of NOPPE and PPE, predict the occurrence of new-onset PE and identify lifestyles that predispose women to postpartum PE. A total of 130 women comprising 65 normotensive postpartum women, 33 NOPPE and 32 PPE women were recruited for this hospital-based case-control study. The socio-demographic and lifestyle characteristics of the participants were obtained through well-structured questionnaires. Haematological and biochemical indices were measured using automated analysers and ELISA. The prevalence of postpartum PE was 11.9%. Dyslipidaemia (p = < 0.0001), hypomagnesaemia (p = < 0.001), elevated serum levels of ALT, AST (p = < 0.0001), sVCAM-1 (p = < 0.0001) and sFlt-1 (p = < 0.0001) were more prevalent and severe in the PPE than in the NOPPE. Sedentary lifestyle was common among both groups of hypertensive women. Elevated ALT and AST were significant predictors of NOPPE. These findings indicate that preeclampsia exists after childbirth in a high percentage of women. NOPPE and PPE are different pathological conditions that require different clinical management. Combined glucose, lipid and liver assessment could be useful in predicting postpartum PE.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Polycystic ovary syndrome (PCOS), a common female endocrinopathy associated with both reproductive and metabolic disorders, has an unclear etiology and unsatisfactory management methods. ...Carboxypeptidase X, M14 family member 1 (CPXM1) is a protein involved in follicular atresia, insulin production, and adipose tissue production, though its role in PCOS is not fully understood. We used a 60% high-fat diet (HFD) plus dehydroepiandrosterone (DHEA)-induced PCOS mouse model to determine the role of CPXM1 in abnormal glucose metabolism and ovarian dysfunction in PCOS. We found that serum CPXM1 concentrations were higher in PCOS mice and positively correlated with increased levels of serum testosterone and insulin. In both ovarian and adipose tissues of PCOS mice, CPXM1 mRNA and protein levels were significantly increased but GLUT4 levels were significantly decreased. Immunohistochemistry (IHC) staining of the ovary showed increased CPXM1 expression in PCOS. In addition, the protein expression of phosphorylated protein kinase B (p-Akt) was also significantly decreased in PCOS mice. Furthermore, mRNA levels of inflammatory markers such as TNF-α, IL-6, IFN-α, and IFN-γ were increased in ovarian and adipose tissues of PCOS mice. However, IRS-1, IRS-2, and INSR levels were significantly decreased. Our results indicated for the first time that abnormally high expression of CPXM1, increased adiposity, impaired glucose tolerance, and chronic low-grade inflammation may act together in a vicious cycle in the pathophysiology of PCOS. Our research suggests the possibility of CPXM1 as a potential therapeutic target for the treatment of PCOS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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