Redox Biol
August 2024
Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP] (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats.
View Article and Find Full Text PDFInt J Mol Sci
January 2024
Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism.
View Article and Find Full Text PDFObjectives: The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra.
Methods: Twelve cats were used and divided into groups: (1) non-gestational healthy diestrus (n = 7) and (2) pyometra (n = 5). The plasma profiles of estradiol and progesterone (P) as well as uterine expression levels of estradiol alpha (ERα), progesterone (PR) and androgen (AR) receptors, of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1), and of the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were evaluated.
We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10.
View Article and Find Full Text PDFSex steroids and antioxidant enzymes modulate uterine and placental physiology. Failures in the expression, signaling, and/or secretion of these mediators are associated with female infertility and gestational problems. However, there is no data on the expression profile of receptors for sex steroids and antioxidant enzymes in the maternal-fetal interface of domestic cats.
View Article and Find Full Text PDFContext: Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway.
Aims: We aimed to evaluate the expression profile of redox and UPR mediators in the placenta of rats throughout pregnancy.
Methods: Placental expression of hypoxia-inducible factor 1α (HIF1α), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (Cat), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), 78 kD glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP), as well as reactive oxygen species (ROS) and peroxynitrite production, were evaluated in Wistar rats on the 10th, 12th, 14th, 16th and 18th day of pregnancy (DP).
Gestational diseases such as preeclampsia and gestational diabetes cause inflammasome activation and pyroptosis in the placenta and changes in placental kisspeptin levels. Although maternal hypothyroidism also reduces the kisspeptin/Kiss1R system at the maternal-fetal interface, there is still no information on whether this dysfunction causes inflammasome activation and pyroptosis in the placenta or influences the modulatory role of kisspeptin in these processes. This study aimed to evaluate whether hypothyroidism activates the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and whether kisspeptin can modulate these processes.
View Article and Find Full Text PDFTheriogenology
June 2023
Sex steroids and antioxidant enzymes are important in female sexual development and adequate modulation of the estrous cycle, pregnancy, and fetal development. Therefore, modifications in its signaling or expression in the genital system are associated with reproductive dysfunctions. However, the spatial-temporal expression profile of receptors for sex steroids and antioxidant enzymes in the uterus of domestic cats throughout the estrous cycle needs to be studied.
View Article and Find Full Text PDFFree Radic Biol Med
October 2022
Maternal hypothyroidism is associated with pre-eclampsia and intrauterine growth restriction, gestational diseases involving oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the placenta. However, it is not known whether hypothyroidism also causes OS and ERS at the maternal-fetal interface. The aim was to evaluate the fetal-placental development and the expression of mediators of OS and of the unfolded protein response (UPR) in the maternal-fetal interface of hypothyroid rats.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
August 2022
Maternal hypothyroidism is associated with fetal growth restriction, placental dysfunction, and reduced kisspeptin/Kiss1R at the maternal-fetal interface. Kisspeptin affects trophoblastic migration and has antioxidant and immunomodulatory activities. This study aimed to evaluate the therapeutic potential of kisspeptin in the fetal-placental dysfunction of hypothyroid Wistar rats.
View Article and Find Full Text PDFHypothyroidism causes ovarian dysfunction and infertility in women, in addition to being associated with hyperprolactinemia and reduced hypothalamic expression of kisspeptin (Kp). However, it remains unknown whether and how Kp is able to reverse the ovarian dysfunction caused by hypothyroidism. Hypothyroidism was induced in adult female Wistar rats using 6-propyl-2-thiouracil for 3 months.
View Article and Find Full Text PDFAlterations of circulating and placental levels of kisspeptin have been associated with gestational diseases. However, there are still no studies on the placental and decidual expression of Kiss1 and its receptor Kiss1r in maternal hypothyroidism, which is the aim of this work. We demonstrate that the fetoplacental restriction caused by hypothyroidism in rats is associated with a reduction in the Kiss1r expression and reduced Kiss1 and Kiss1r mRNA levels in the decidua and/or placenta.
View Article and Find Full Text PDFThe Kisspeptin/Kiss1r system has been studied in mammalian ovaries. However, there are still no studies on the modulation of this system and its relationship with angiogenic and immunological mediators in the ovary of domestic cats, especially during pregnancy. We evaluated the expression of Kisspeptin/Kiss1r and angiogenic and immunological mediators during folliculogenesis, luteogenesis and luteal regression of cyclic and pregnant cats.
View Article and Find Full Text PDFThe Kisspeptin/Kiss1r system is a key regulator of reproduction by stimulating gonadotrophin-releasing hormone and luteinizing hormone release, and in vitro studies have shown that Kisspeptin can modulate angiogenesis and immune function, factors that are also essential for reproduction However, there are no studies on the expression of Kisspeptin/Kiss1r at the maternal-fetal interface in domestic cats and its relationship with angiogenic and immunological mediators. Thus, our objective was to evaluate the spatiotemporal expression profile of Kisspeptin/Kiss1r and angiogenic and immunological mediators in the uterus and placenta of domestic cats during pregnancy. Uterus and placenta samples were collected from cats in mid pregnancy (N = 6) and late pregnancy (N = 6), in addition to uterus from non-pregnant cats in diestrus (N = 7), to evaluate protein and gene expression of kisspeptin (Kiss1), kisspeptin receptor (Kiss1r), vascular endothelial growth factor (VEGF), tyrosine kinase receptor (Flk-1), placental growth factor (PLGF), interferon gamma (INFγ), migration inhibiting factor (MIF), tumor necrosis factor (TNFα), interleukins (IL6 and IL10) by immunohistochemistry and quantitative polymerase chain reaction.
View Article and Find Full Text PDFFailures in hypothalamic kisspeptin/Kiss1r signaling are associated with infertility, and in vitro studies have shown that kisspeptin can modulate angiogenesis and immune activity. Because there is no in vivo research on the functional relationship between these factors in the reproductive system, especially in domestic cats, we evaluated the expression profile of kisspeptin/Kiss1r and angiogenic and immunological mediators in the genital tract of cyclic cats and of those with pyometra. The uterus of cats in diestrus exhibited greater gene and protein expression of Kiss1, as well as Vegf, Pigf, Mif, and Il6.
View Article and Find Full Text PDFThe demand for new therapies has encouraged the development of faster and cheaper methods of drug design. Considering the number of potential biological targets for new drugs, the docking-based virtual screening (DBVS) approach has occupied a prominent role among modern strategies for identifying new bioactive substances. Some tools have been developed to validate docking methodologies and identify false positives, such as the receiver operating characteristic (ROC) curve.
View Article and Find Full Text PDFOctopus is an automated workflow management tool that is scalable for virtual high-throughput screening (vHTS). It integrates MOPAC2016, MGLTools, PyMOL, and AutoDock Vina. In contrast to other platforms, Octopus can perform docking simulations of an unlimited number of compounds into a set of molecular targets.
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