Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.
The coronavirus disease 2019 (COVID-19) pandemic is a global health challenge with substantial adverse effects on the world economy. It is beyond any doubt that it is, again, a call-to-action to minimize the risk of future zoonoses caused by emerging human pathogens. The primary response to contain zoonotic diseases is to call for more strict regulations on wildlife trade and hunting. This is because the origins of coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), as well as other viral pathogens (e.g., Ebola, HIV) are traceable to wild animals. Although COVID-19 is not related to livestock animals, the pandemic increased general attention given to zoonotic viral infections—the risk of which can also be associated with livestock. Therefore, this paper discusses the potential transformation of industrial livestock farming and the production of animal products, particularly meat, to decrease the risks for transmission of novel human pathogens. Plant-based diets have a number of advantages, but it is unrealistic to consider them as the only solution offered to the problem. Therefore, a search for alternative protein sources in insect-based foods and cultured meat, important technologies enabling safer meat production. Although both of these strategies offer a number of potential advantages, they are also subject to the number of challenges that are discussed in this paper. Importantly, insect-based foods and cultured meat can provide additional benefits in the context of ecological footprint, an aspect important in light of predicted climate changes. Furthermore, cultured meat can be regarded as ethically superior and supports better food security. There is a need to further support the implementation and expansion of all three approaches discussed in this paper, plant-based diets, insect-based foods, and cultured meat, to decrease the epidemiological risks and ensure a sustainable future. Furthermore, cultured meat also offers a number of additional benefits in the context of environmental impact, ethical issues, and food security.
The physiological processes that drive the development of ovarian follicle, as well as the process of oogenesis, are quite well known. Granulosa cells are major players in this occurrence, being the somatic element of the female gamete development. They participate directly in the processes of oogenesis, building the cumulus-oocyte complex surrounding the ovum. In addition to that, they have a further impact on the reproductive processes, being a place of steroid sex hormone synthesis and secretion. It is known that the follicle development creates a major need for angiogenesis and blood vessel development in the ovary. In this study, we use novel molecular approaches to analyze markers of these processes in porcine granulosa cultured primarily in vitro. The cells were recovered from mature sus scrofa specimen after slaughter. They were then subjected to enzymatic digestion and culture primarily for a short term. The RNA was extracted from cultures in specific time periods (0h, 24h, 48h, 96h, and 144h) and analyzed using expression microarrays. The genes that exhibited fold change bigger than |2|, and adjusted p-value lower than 0.05, were considered differentially expressed. From these, we have chosen the members of “angiogenesis,” “blood vessel development,” “blood vessel morphogenesis,” “cardiovascular system development,” and “vasculature development” for further selection. CCL2, FGFR2, SFRP2, PDPN, DCN, CAV1, CHI3L1, ITGB3, FN1, and LOX which are upregulated, as well as CXCL10, NEBL, IHH, TGFBR3, SCUBE1, IGF1, EDNRA, RHOB, PPARD, and SLITRK5 genes whose expression is downregulated through the time of culture, were chosen as the potential markers, as their expression varied the most during the time of culture. The fold changes were further validated with RT-qPCR. The genes were described, with special attention to their possible function in GCs during culture. The results broaden the general knowledge about GC’s in vitro molecular processes and might serve as a point of reference for further in vivo and clinical studies.
Granulosa cells (GCs) have many functions in the endocrine system. Most notably, they produce progesterone following ovulation. However, it has recently been proven that GCs can change their properties when subjected to long-term culture. In the present study, GCs were collected from hyper-stimulated ovarian follicles during in vitro fertilization procedures. They were grown in vitro , in a long-term manner. RNA was collected following 1, 7, 15 and 30 days of culture. Expression microarrays were used for analysis, which allowed to identify groups of genes characteristic for particular cellular processes. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to validate the obtained results. Two ontological groups characteristic for processes associated with the development and morphogenesis of the heart were identified during the analyses: ‘Heart development’ and ‘heart morphogenesis’. The results of the microarrays revealed that the highest change in expression was demonstrated by the lysyl Oxidase, oxytocin receptor, nexilin F-actin binding protein , and cysteine-rich protein 3 genes. The lowest change was exhibited by odd-skipped related transcription factor 1, plakophilin 2, transcription growth factor-β receptor 1 , and kinesin family member 3A . The direction of changes was confirmed by RT-qPCR results. In the present study, it was suggested that GCs may have the potential to differentiate towards other cell types under long-term in vitro culture conditions. Thus, genes belonging to the presented ontological groups can be considered as novel markers of proliferation and differentiation of GCs towards the heart muscle cells.
Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic β-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.
Ovarian Granulosa Cells (GCs) are known to proliferate in the developing follicle and undergo several biochemical processes during folliculogenesis. They represent a multipotent cell population that has been differentiated to neuronal cells, chondrocytes, and osteoblasts in vitro. However, progression and maturation of GCs are accompanied by a reduction in their stemness. In the developing follicle, GCs communicate with the oocyte bidirectionally via gap junctions. Together with neighboring theca cells, they play a crucial role in steroidogenesis, particularly the production of estradiol, as well as progesterone following luteinization. Many signaling pathways are known to be important throughout the follicle development, leading either towards luteinization and release of the oocyte, or follicular atresia and apoptosis. These signaling pathways include cAMP, PI3K, SMAD, Hedgehog (HH), Hippo and Notch, which act together in a complex manner to control the maturation of GCs through regulation of key genes, from the primordial follicle to the luteal phase. Small molecules such as resveratrol, a phytoalexin found in grapes, peanuts and other dietary constituents, may be able to activate/inhibit these signaling pathways and thereby control physiological properties of GCs. This article reviews the current knowledge about granulosa stem cells, the signaling pathways driving their development and maturation, as well as biological activities of resveratrol and its properties as a pro-differentiation agent.
The pig is a polyestrous animal in which the ovarian cycle lasts about 21 days and results in ovulation of 10-25 oocytes. Ovum reaches 120-150 μm in diameter, with the surrounding corona radiata providing communication with the environment. The zona pellucida is composed of glycoproteins: ZP1, ZP2, ZP3. In the course of oogenesis, RNA and protein accumulation for embryonic development occurs. Maternal mRNA is the template for protein production. Nuclear, cytoplasmic and genomic maturity condition the ability of the ovum to undergo fertilization. There are several differences in protein expression profiles observed between in vitro and in vivo conditions. Oogenesis is the process of differentiating female primary sex cells into gametes. During development gonocytes migrate from the yolk sac into the primary gonads with TGF-1, fibronectin, and laminin regulating this process. Cell cycle is blocked in dictyotene. Primary oocyte maturation is resumed before each ovulation and lasts until the next block in metaphase II. At the moment of penetration of the sperm into the ovum, the metaphase block is broken. The oocytes, surrounded by a single layer of granular cells, form the ovarian follicle. The exchange of signals between the oocyte and the cumulus cells done by gap-junctions, as well as various endo and paracrine signals. The contact between the corona radiata cells provides substances necessary for growth, through the same gap junctions. Studies on follicular cells can be used to amplify the knowledge of gene expression in these cells, in order to open way for potential clinical applications. Running title: ovarian cysts formation
The deterioration of the human skeleton’s capacity for self-renewal occurs naturally with age. Osteoporosis affects millions worldwide, with current treatments including pharmaceutical agents that target bone formation and/or resorption. Nevertheless, these clinical approaches often result in long-term side effects, with better alternatives being constantly researched. Mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue are known to hold therapeutic value for the treatment of a variety of bone diseases. The following review summarizes the latest studies and clinical trials related to the use of MSCs, both individually and combined with other methods, in the treatment of a variety of conditions related to skeletal health. For example, some of the most recent works noted the advantage of bone grafts based on biomimetic scaffolds combined with MSC and growth factor delivery, with a greatly increased regeneration rate and minimized side effects for patients. This review also highlights the continuing research into the mechanisms underlying bone homeostasis, including the key transcription factors and signalling pathways responsible for regulating the differentiation of osteoblast lineage. Paracrine factors and specific miRNAs are also believed to play a part in MSC differentiation. Furthering the understanding of the specific mechanisms of cellular signalling in skeletal remodelling is key to incorporating new and effective treatment methods for bone disease.
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