Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age; however, its aetiology is unclear. PCOS is linked to many metabolic manifestations and alterations such as obesity, insulin resistance, and cardiovascular diseases (CVD). Women with PCOS have intra-ovarian and systemic changes in their metabolite levels. Adipose tissue dysfunction plays a significant role in the pathophysiology of PCOS. Adipose tissue growth is disrupted by metabolic stress, leading to hypertrophy of adipocytes, which begin to express stress signals. Adipose tissue secretes autocrine and paracrine factors, called adipokines or adipocytokines. Adiponectin is an adipocyte-derived protein abundant in the bloodstream. Plasma adiponectin concentration is low in women with PCOS, obesity, CVD, and hypertension. Other adipocytokines with altered secretion in PCOS include leptin, resistin, apelin, visfatin, IL-6, IL-8, and TNF-α. Hormonal imbalance, untimely action of high LH, and consequent hyperandrogenism in women with PCOS may cause metabolic defects associated with adipose tissue dysfunction; however, there are no reports on the role of higher LH levels in adipose dysfunction and altered adipokine secretion. New medications with therapeutic potential have been developed that target adipokines for the treatment of PCOS. This review discusses the association between PCOS and altered adipokine production as a consequence of adipose dysfunction.
{"title":"Adipose Tissue Dysfunction in PCOS","authors":"Ananya Aparupa, Rita Singh","doi":"10.18311/jer/2023/34082","DOIUrl":"https://doi.org/10.18311/jer/2023/34082","url":null,"abstract":"Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age; however, its aetiology is unclear. PCOS is linked to many metabolic manifestations and alterations such as obesity, insulin resistance, and cardiovascular diseases (CVD). Women with PCOS have intra-ovarian and systemic changes in their metabolite levels. Adipose tissue dysfunction plays a significant role in the pathophysiology of PCOS. Adipose tissue growth is disrupted by metabolic stress, leading to hypertrophy of adipocytes, which begin to express stress signals. Adipose tissue secretes autocrine and paracrine factors, called adipokines or adipocytokines. Adiponectin is an adipocyte-derived protein abundant in the bloodstream. Plasma adiponectin concentration is low in women with PCOS, obesity, CVD, and hypertension. Other adipocytokines with altered secretion in PCOS include leptin, resistin, apelin, visfatin, IL-6, IL-8, and TNF-α. Hormonal imbalance, untimely action of high LH, and consequent hyperandrogenism in women with PCOS may cause metabolic defects associated with adipose tissue dysfunction; however, there are no reports on the role of higher LH levels in adipose dysfunction and altered adipokine secretion. New medications with therapeutic potential have been developed that target adipokines for the treatment of PCOS. This review discusses the association between PCOS and altered adipokine production as a consequence of adipose dysfunction.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"32 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Endometriosis is a chronic inflammatory condition of high incidence and with serious consequences. Several synthetic compounds proved to be useful in treating its symptoms by inhibiting aromatase, which is responsible for the pathogenesis of this painful illness. Nevertheless, synthetic drugs inflict several side effects, including headaches, osteoporosis, and so on. This scenario advocates the search for therapeutic formulations based on natural compounds. Thus, the present study was hypothesized to evaluate the comparative efficacy of the synthetic and natural drugs used in endometriosis, using the bioinformatics approach. Methods: CB-Dock was employed to perform molecular docking of the aromatase enzyme with two synthetic and three natural drugs for predicting their molecular interactions, and binding affinities. The curcumin-aromatase complex was further subjected to MD simulations to determine its stability, and to apply it to natural compound-based computer-aided drug discovery. Results: Curcumin was observed to dock with a greater binding interaction with aromatase. The RMSD profile, hydrogen bonds, and the RMSF and Rg values of the complex were stabilised after 50 ns, which was an indicator of the stable binding pose of the curcumin-aromatase complex. Conclusion: These in-silico findings are the basis for proposing that curcumin can be considered as a potential binding agent to inhibit the aromatase enzyme in the treatment of endometriosis. Molecular modelling and dynamics results suggest that curcumin and aromatase form a stable complex and that curcumin can be targeted as a drug in the treatment of endometriosis
{"title":"Evaluating the Relative Efficacy of Synthetic and Natural Drugs in Endometriosis Adopting Molecular Modelling Approach","authors":"Indra Singh, Ranjit Shaw, Pritha Saha, Krishna Kumar Ojha, Radha Chaube","doi":"10.18311/jer/2023/33854","DOIUrl":"https://doi.org/10.18311/jer/2023/33854","url":null,"abstract":"Background: Endometriosis is a chronic inflammatory condition of high incidence and with serious consequences. Several synthetic compounds proved to be useful in treating its symptoms by inhibiting aromatase, which is responsible for the pathogenesis of this painful illness. Nevertheless, synthetic drugs inflict several side effects, including headaches, osteoporosis, and so on. This scenario advocates the search for therapeutic formulations based on natural compounds. Thus, the present study was hypothesized to evaluate the comparative efficacy of the synthetic and natural drugs used in endometriosis, using the bioinformatics approach. Methods: CB-Dock was employed to perform molecular docking of the aromatase enzyme with two synthetic and three natural drugs for predicting their molecular interactions, and binding affinities. The curcumin-aromatase complex was further subjected to MD simulations to determine its stability, and to apply it to natural compound-based computer-aided drug discovery. Results: Curcumin was observed to dock with a greater binding interaction with aromatase. The RMSD profile, hydrogen bonds, and the RMSF and Rg values of the complex were stabilised after 50 ns, which was an indicator of the stable binding pose of the curcumin-aromatase complex. Conclusion: These in-silico findings are the basis for proposing that curcumin can be considered as a potential binding agent to inhibit the aromatase enzyme in the treatment of endometriosis. Molecular modelling and dynamics results suggest that curcumin and aromatase form a stable complex and that curcumin can be targeted as a drug in the treatment of endometriosis","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"25 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Priyal Sharma, Manish Jain, Manish Tripathi, Mona Sharma, A. Halder
PCOS is a common endocrinopathy among women of reproductive age, with a worldwide prevalence of 8 to 13%, depending on the criteria used for diagnosis. It is characterized by a constellation of features, including oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. PCOS is one of the common causes of female infertility. It is also associated with metabolic derangements, including obesity, insulin resistance, and compensatory hyperinsulinemia, which increase the likelihood of developing type 2 diabetes mellitus. Despite extensive research, the etiology of PCOS remains largely unknown. It seems likely that the hypothalamic-pituitary-ovarian axis dysfunction, partial folliculogenesis arrest, insulin resistance, and ovarian and adrenal androgen secretion may play a role in the pathogenesis of PCOS. Familial clustering of the cases of PCOS points to a genetic component linked with it. The initial genetic studies suggest an autosomal dominant pattern of inheritance of the disorder in some families; however, most studies support multifactorial origin. Since PCOS is a complex trait, the typical form of inheritance of PCOS follows a non-Mendelian pattern and involves complex genetic mechanisms. Studies involving linkage and association have suggested a connection between genetic variations and the risk of developing PCOS in certain families or populations. Through genome-wide association studies and next-generation sequencing techniques, several candidate genes have been identified that play a role in the etiopathogenesis of the disorder. Pathogenic variants of various genes such as INSR, IRS1, GHRL, LDLR, MC4R, ADIPOQ, UCP1, UCP2, UCP3, FTO, PCSK9, FBN3, NEIL2, FDFT1, PCSK9, CYP11, CYP17, CYP21, HSD17, STAR, POR, AKR1C3, AMH, AMHR2, INHBA, AR, SHBG, LHR, FSHR, FSH β, SRD5A, GATA4, THADA, YAP1, ERBB2, DENND1A, FEM1B, FDFT1, NEIL2, TCF7L2, etc. in some PCOS cases are linked as underlying etiologic associations. This review aims to provide insight into the current genetic knowledge about PCOS. Discovering the genetic factors and pathways involved in the disorder will help us better comprehend the underlying mechanisms of the disorder.
{"title":"An Update on the Genetics of Polycystic Ovary Syndrome","authors":"Priyal Sharma, Manish Jain, Manish Tripathi, Mona Sharma, A. Halder","doi":"10.18311/jer/2023/34654","DOIUrl":"https://doi.org/10.18311/jer/2023/34654","url":null,"abstract":"PCOS is a common endocrinopathy among women of reproductive age, with a worldwide prevalence of 8 to 13%, depending on the criteria used for diagnosis. It is characterized by a constellation of features, including oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. PCOS is one of the common causes of female infertility. It is also associated with metabolic derangements, including obesity, insulin resistance, and compensatory hyperinsulinemia, which increase the likelihood of developing type 2 diabetes mellitus. Despite extensive research, the etiology of PCOS remains largely unknown. It seems likely that the hypothalamic-pituitary-ovarian axis dysfunction, partial folliculogenesis arrest, insulin resistance, and ovarian and adrenal androgen secretion may play a role in the pathogenesis of PCOS. Familial clustering of the cases of PCOS points to a genetic component linked with it. The initial genetic studies suggest an autosomal dominant pattern of inheritance of the disorder in some families; however, most studies support multifactorial origin. Since PCOS is a complex trait, the typical form of inheritance of PCOS follows a non-Mendelian pattern and involves complex genetic mechanisms. Studies involving linkage and association have suggested a connection between genetic variations and the risk of developing PCOS in certain families or populations. Through genome-wide association studies and next-generation sequencing techniques, several candidate genes have been identified that play a role in the etiopathogenesis of the disorder. Pathogenic variants of various genes such as INSR, IRS1, GHRL, LDLR, MC4R, ADIPOQ, UCP1, UCP2, UCP3, FTO, PCSK9, FBN3, NEIL2, FDFT1, PCSK9, CYP11, CYP17, CYP21, HSD17, STAR, POR, AKR1C3, AMH, AMHR2, INHBA, AR, SHBG, LHR, FSHR, FSH β, SRD5A, GATA4, THADA, YAP1, ERBB2, DENND1A, FEM1B, FDFT1, NEIL2, TCF7L2, etc. in some PCOS cases are linked as underlying etiologic associations. This review aims to provide insight into the current genetic knowledge about PCOS. Discovering the genetic factors and pathways involved in the disorder will help us better comprehend the underlying mechanisms of the disorder.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"26 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farha Yasmin, Sona Sutradhar, Arun Roy, Russel Sarkar, Sourav Mukherjee
The dietary protein, tryptophan, carbohydrate, and oil content of fish feed has many vital roles in the growth performances, stress management, and digestive physiology of fish. However, in this context, the functions of gut melatonin, which depends on the availability of food, timing of food supply, frequency of feeds/day, quality of food, and growth stages of carp, still need to be clarified. The present study aimed to investigate the impact of different experimental diets on growth performances, melatonin, oxidative stress and its essential antioxidants in the gut, and vital digestive enzymes of juvenile carp, Catla catla (mean body weight ~50g). The fish were fed any one of the seven diets viz. (i) a standard diet (SD/control) (with 34.99% protein, 14.56% carbohydrate, 9.84% oil, and 0.36% L-tryptophan) (ii) two protein (PRD1 with 41.02%, and PRD2 with 50.55% protein), (iii) two L-tryptophan (TrpRD1 with 0.96%, and TrpRD2 with 1.36% tryptophan), (iv) one carbohydrate (CRD with 24.62% carbohydrate), and (v) one oil (ORD with 14.68% oil) - rich diets for 30 days. Results indicated that the growth performance was better in PRDs, TrpRDs, and CRD compared to SD but not in ORD-fed carp. Further, PRDs and TrpRDs stimulated gut melatonin and suppressed oxidative stress by enhancing all the studied antioxidant levels. Upregulated digestive enzyme activities were also recorded after the PRDs and TrpRDs supply. However, CRD and ORD-fed groups exhibit less/no impact on most studied parameters, except digestive physiology. Nonetheless, the current study reports for the first time that PRDs and TrpRDs can modulate gut melatonin, oxidative stress, different antioxidants, and digestive efficacy.
{"title":"Impacts of Protein-, L-Tryptophan-, Carbohydrate-, Oil-Rich Diets on Growth Performance, Levels of Melatonin, Oxidative Stress, Antioxidative Agents, and Vital Digestive Enzymes in the Gut of Juvenile Carp (Catla catla)","authors":"Farha Yasmin, Sona Sutradhar, Arun Roy, Russel Sarkar, Sourav Mukherjee","doi":"10.18311/jer/2023/34512","DOIUrl":"https://doi.org/10.18311/jer/2023/34512","url":null,"abstract":"The dietary protein, tryptophan, carbohydrate, and oil content of fish feed has many vital roles in the growth performances, stress management, and digestive physiology of fish. However, in this context, the functions of gut melatonin, which depends on the availability of food, timing of food supply, frequency of feeds/day, quality of food, and growth stages of carp, still need to be clarified. The present study aimed to investigate the impact of different experimental diets on growth performances, melatonin, oxidative stress and its essential antioxidants in the gut, and vital digestive enzymes of juvenile carp, Catla catla (mean body weight ~50g). The fish were fed any one of the seven diets viz. (i) a standard diet (SD/control) (with 34.99% protein, 14.56% carbohydrate, 9.84% oil, and 0.36% L-tryptophan) (ii) two protein (PRD1 with 41.02%, and PRD2 with 50.55% protein), (iii) two L-tryptophan (TrpRD1 with 0.96%, and TrpRD2 with 1.36% tryptophan), (iv) one carbohydrate (CRD with 24.62% carbohydrate), and (v) one oil (ORD with 14.68% oil) - rich diets for 30 days. Results indicated that the growth performance was better in PRDs, TrpRDs, and CRD compared to SD but not in ORD-fed carp. Further, PRDs and TrpRDs stimulated gut melatonin and suppressed oxidative stress by enhancing all the studied antioxidant levels. Upregulated digestive enzyme activities were also recorded after the PRDs and TrpRDs supply. However, CRD and ORD-fed groups exhibit less/no impact on most studied parameters, except digestive physiology. Nonetheless, the current study reports for the first time that PRDs and TrpRDs can modulate gut melatonin, oxidative stress, different antioxidants, and digestive efficacy.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"66 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell-intrinsic early events involved in different trophic hormone-induced steroidogenesis in their respective steroidogenic cell type are very similar. For example, the activation of the cAMP-PKA signaling pathway in response to trophic hormone stimulation and, subsequently, cholesterol transport to the mitochondria to initiate steroidogenesis is common to them. Recently, we have found that an evolutionarily conserved protein, prohibitin-1 (PHB1), is regulated by Luteinizing Hormone (LH) in murine Leydig cells and plays a role in interconnected cell signaling and mitochondrial steps pertaining to testosterone production. Among the primary steroidogenic tissues, PHB1 expression levels are highest in the adrenal cortex (The Human Protein Atlas); however, its regulation and role in adrenocortical cells are virtually unknown. We investigated the regulation and the role of PHB1 in adrenocortical cells in vitro using human HAC15 and mouse Y-1 cell culture models. It was found that Adrenocorticotrophic Hormone (ACTH) stimulation upregulates PHB1 levels in adrenocortical cells in a time-dependent manner. A similar effect on PHB1 levels was also observed in response to dibutyryl-cAMP stimulation, a cell-permeable analogue of cAMP (the second messenger for ACTH action). Moreover, manipulating PHB1 levels in adrenocortical cells affected mitochondria, lysosomes, and lipid droplet characteristics, modulated phospho-PKA and phospho-ERK1/2 levels, and altered corticosteroid production. This finding suggests that ACTH regulates PHB1 in adrenocortical cells and plays a role in corticosteroid production, which was previously unknown.
不同营养激素诱导的甾体生成细胞类型的细胞内在早期事件是非常相似的。例如，cAMP-PKA信号通路在营养激素刺激下的激活，以及随后胆固醇转运到线粒体以启动类固醇生成对它们来说是共同的。最近，我们发现了一种进化上保守的蛋白，禁止素-1 (PHB1)，在小鼠间质细胞中受黄体生成素(LH)的调节，并在与睾酮产生有关的相互连接的细胞信号传导和线粒体步骤中发挥作用。在原发性类固醇生成组织中，PHB1在肾上腺皮质的表达水平最高(the Human Protein Atlas);然而，它在肾上腺皮质细胞中的调节和作用几乎是未知的。我们利用人HAC15和小鼠Y-1细胞培养模型，研究了PHB1在体外肾上腺皮质细胞中的调控作用。研究发现，促肾上腺皮质激素(ACTH)刺激以一种时间依赖性的方式上调肾上腺皮质细胞中的PHB1水平。二丁基cAMP刺激对PHB1水平也有类似的影响，二丁基cAMP是一种细胞渗透性类似物(ACTH作用的第二信使)。此外，控制肾上腺皮质细胞中的PHB1水平会影响线粒体、溶酶体和脂滴特性，调节磷酸化pka和磷酸化erk1 /2水平，并改变皮质类固醇的产生。这一发现表明ACTH调节肾上腺皮质细胞中的PHB1，并在皮质类固醇的产生中发挥作用，这在以前是未知的。
{"title":"Prohibitin-1 is an ACTH-Regulated Protein in Human and Mouse Adrenocortical Cells and Plays a Role in Corticosteroid Production","authors":"Suresh Mishra, Simarjit Kaur Sidhu, Geetika Bassi","doi":"10.18311/jer/2023/34993","DOIUrl":"https://doi.org/10.18311/jer/2023/34993","url":null,"abstract":"Cell-intrinsic early events involved in different trophic hormone-induced steroidogenesis in their respective steroidogenic cell type are very similar. For example, the activation of the cAMP-PKA signaling pathway in response to trophic hormone stimulation and, subsequently, cholesterol transport to the mitochondria to initiate steroidogenesis is common to them. Recently, we have found that an evolutionarily conserved protein, prohibitin-1 (PHB1), is regulated by Luteinizing Hormone (LH) in murine Leydig cells and plays a role in interconnected cell signaling and mitochondrial steps pertaining to testosterone production. Among the primary steroidogenic tissues, PHB1 expression levels are highest in the adrenal cortex (The Human Protein Atlas); however, its regulation and role in adrenocortical cells are virtually unknown. We investigated the regulation and the role of PHB1 in adrenocortical cells in vitro using human HAC15 and mouse Y-1 cell culture models. It was found that Adrenocorticotrophic Hormone (ACTH) stimulation upregulates PHB1 levels in adrenocortical cells in a time-dependent manner. A similar effect on PHB1 levels was also observed in response to dibutyryl-cAMP stimulation, a cell-permeable analogue of cAMP (the second messenger for ACTH action). Moreover, manipulating PHB1 levels in adrenocortical cells affected mitochondria, lysosomes, and lipid droplet characteristics, modulated phospho-PKA and phospho-ERK1/2 levels, and altered corticosteroid production. This finding suggests that ACTH regulates PHB1 in adrenocortical cells and plays a role in corticosteroid production, which was previously unknown.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135887503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Captive breeding has become an important tool for conserving threatened species. The success of these conservation programs depends on the survival of species through self-sustaining populations managed by scientific values. Mouse deer is a primitive deer that plays a crucial role in the forest ecosystem as a key seed disperser and forms significant prey for both small and large predators. Despite its significance, little is known about this species' mating behavior and reproductive physiology in both the wild and captivity. As part of the conservation breeding and species recovery program, a breeding program of mouse deer started with the aim of breeding them in captivity and release them into the wild to preserve the biodiversity. This program began with six founder individuals and we observed a remarkable increase of 400 individuals within 10 years. These captive-bred individuals have been successfully introduced into the wild. This paper presents a comprehensive review of potential factors required for the successful breeding program and also provides recommendations on future directions and perspectives of conservation breeding program of mouse deer and other species.
{"title":"From Captivity to Conservation Success: A Review on the Mouse Deer Breeding Program and its Implications for Biodiversity Preservation","authors":"Vinod Kumar, Govindhaswamy Umapathy","doi":"10.18311/jer/2023/34990","DOIUrl":"https://doi.org/10.18311/jer/2023/34990","url":null,"abstract":"Captive breeding has become an important tool for conserving threatened species. The success of these conservation programs depends on the survival of species through self-sustaining populations managed by scientific values. Mouse deer is a primitive deer that plays a crucial role in the forest ecosystem as a key seed disperser and forms significant prey for both small and large predators. Despite its significance, little is known about this species' mating behavior and reproductive physiology in both the wild and captivity. As part of the conservation breeding and species recovery program, a breeding program of mouse deer started with the aim of breeding them in captivity and release them into the wild to preserve the biodiversity. This program began with six founder individuals and we observed a remarkable increase of 400 individuals within 10 years. These captive-bred individuals have been successfully introduced into the wild. This paper presents a comprehensive review of potential factors required for the successful breeding program and also provides recommendations on future directions and perspectives of conservation breeding program of mouse deer and other species.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135887161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sean Campos, Mikayla Ybarra, Jonathan Madeti, Rebecca A. Garcia
Plasmodium is a parasite that can infect red blood cells and cause flu-like symptoms with malaria infection. Traditional diagnostic methods do not include counting or testing for gametocytes, which can reservoir in the liver for long periods of time and recirculate. These carriers may have no symptoms, but they can transmit infection to others or to mosquitos. Currently, no diagnostic tests have been approved to detect Plasmodium gametocytes in either symptomatic or asymptomatic whole blood samples. Therefore, we developed real-time PCR assays to detect active and carrier states of malaria. The first is a traditional screening test that can detect any of the five Plasmodium species that cause malaria infection. The second is a companion test to differentiate and quantitate Plasmodium falciparum and P. vivax gametocytes in samples of whole blood from patients who may be asymptomatic and present negative results from screening tests. The screening test showed amplification of P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi in saliva with an overall detection limit of 565 copies/μL. The gametocyte test showed no cross-reactivity between P. falciparum and P. vivax with a limit of detection of RNA at 1000 copies/μL.
{"title":"Advances in Malaria Testing: Screening and Identification of Carriers from Saliva","authors":"Sean Campos, Mikayla Ybarra, Jonathan Madeti, Rebecca A. Garcia","doi":"10.18311/jer/2023/34266","DOIUrl":"https://doi.org/10.18311/jer/2023/34266","url":null,"abstract":"Plasmodium is a parasite that can infect red blood cells and cause flu-like symptoms with malaria infection. Traditional diagnostic methods do not include counting or testing for gametocytes, which can reservoir in the liver for long periods of time and recirculate. These carriers may have no symptoms, but they can transmit infection to others or to mosquitos. Currently, no diagnostic tests have been approved to detect Plasmodium gametocytes in either symptomatic or asymptomatic whole blood samples. Therefore, we developed real-time PCR assays to detect active and carrier states of malaria. The first is a traditional screening test that can detect any of the five Plasmodium species that cause malaria infection. The second is a companion test to differentiate and quantitate Plasmodium falciparum and P. vivax gametocytes in samples of whole blood from patients who may be asymptomatic and present negative results from screening tests. The screening test showed amplification of P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi in saliva with an overall detection limit of 565 copies/μL. The gametocyte test showed no cross-reactivity between P. falciparum and P. vivax with a limit of detection of RNA at 1000 copies/μL.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135887165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproduction depends on the responses of gonadotropins through their specific receptors. The gonadotropin family has three members; Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Human Chorionic Gonadotropin (hCG). These glycoprotein hormones comprise two subunits, an identical α-subunit and a hormone-specific-β subunit. Their cognate receptors (FSHR and LHCGR) are two adrenergic receptor-like family A/rhodopsin-like G-Protein Coupled Receptors (GPCRs) with structurally distinct ligand binding domains. The hCG binds to LHCGR but has a longer half-life and higher affinity to LHCGR. The expression of FSHR and LHCGR is observed in both gonadal and nongonadal cells. In this review, we will be emphasizing the differential expression of gonadotropin receptors in different cells of the human body, their specific responses through cross-talk, and how a defect in the expression and activity of FSHR and LHCGR may alter the responses of FSH and LH/hCG leading to diseases like PCOS, cancer and metabolic disorders.
{"title":"Gonadotropin Receptor Cross-Talk and Altered Functions in Gonadal and Non-Gonadal Tissues","authors":"Rita Singh, Anjali Pathak","doi":"10.18311/jer/2023/34991","DOIUrl":"https://doi.org/10.18311/jer/2023/34991","url":null,"abstract":"Reproduction depends on the responses of gonadotropins through their specific receptors. The gonadotropin family has three members; Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Human Chorionic Gonadotropin (hCG). These glycoprotein hormones comprise two subunits, an identical α-subunit and a hormone-specific-β subunit. Their cognate receptors (FSHR and LHCGR) are two adrenergic receptor-like family A/rhodopsin-like G-Protein Coupled Receptors (GPCRs) with structurally distinct ligand binding domains. The hCG binds to LHCGR but has a longer half-life and higher affinity to LHCGR. The expression of FSHR and LHCGR is observed in both gonadal and nongonadal cells. In this review, we will be emphasizing the differential expression of gonadotropin receptors in different cells of the human body, their specific responses through cross-talk, and how a defect in the expression and activity of FSHR and LHCGR may alter the responses of FSH and LH/hCG leading to diseases like PCOS, cancer and metabolic disorders.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135886987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
One challenge that needs to be addressed in animal embryo production is to create the appropriate in vitro culture to improve the blastocyst rate and produce high-quality embryos. Buffalo Mesenchymal Stem Cells (MSCs) were derived from Wharton’s jelly and expanded in vitro. Conditioned media (secretome) was collected from well-characterized WJMSCs at 3rd passage. Similarly, buffalo Uterine Epithelial Cells (UECs) were derived from nongravid uteri and expanded in vitro. The secretome was collected from a well-characterized first passage UECs monolayer primed with steroid hormones (progesterone 3.14ng/ml and estradiol-17β 5 31pg/ml). Culture media was replaced with non-serum media, and the media was collected after 72h. Day 4 IVF-derived embryos were cultured in three groups: in regular mSOF media (Group I), mSOF replaced with 50% CM derived from MSCs (Group II), and mSOF replaced with 50% CM from steroid-treated UECs (Group III). Blastocyst rates were evaluated on day 09 post IVF. The blastocyst rate in group II was significantly higher (p < 0.05) than the control group, which was further enhanced in group III. In vitro co-culture of embryos with the secretome derived from mesenchymal stem cells or steroid-treated UECs improved the blastocyst rate. UECs and their secretions are essential to establish uterine receptivity and to mimic the internal in vivo environment.
{"title":"Elucidating the Impact of Secretome Derived from Mesenchymal Stem Cell and Uterine Epithelial Cells During <i>In Vitro</i> Blastocyst Production in Buffalo","authors":"Vikash Chandra, G. Taru Sharma","doi":"10.18311/jer/2023/34992","DOIUrl":"https://doi.org/10.18311/jer/2023/34992","url":null,"abstract":"One challenge that needs to be addressed in animal embryo production is to create the appropriate in vitro culture to improve the blastocyst rate and produce high-quality embryos. Buffalo Mesenchymal Stem Cells (MSCs) were derived from Wharton’s jelly and expanded in vitro. Conditioned media (secretome) was collected from well-characterized WJMSCs at 3rd passage. Similarly, buffalo Uterine Epithelial Cells (UECs) were derived from nongravid uteri and expanded in vitro. The secretome was collected from a well-characterized first passage UECs monolayer primed with steroid hormones (progesterone 3.14ng/ml and estradiol-17β 5 31pg/ml). Culture media was replaced with non-serum media, and the media was collected after 72h. Day 4 IVF-derived embryos were cultured in three groups: in regular mSOF media (Group I), mSOF replaced with 50% CM derived from MSCs (Group II), and mSOF replaced with 50% CM from steroid-treated UECs (Group III). Blastocyst rates were evaluated on day 09 post IVF. The blastocyst rate in group II was significantly higher (p < 0.05) than the control group, which was further enhanced in group III. In vitro co-culture of embryos with the secretome derived from mesenchymal stem cells or steroid-treated UECs improved the blastocyst rate. UECs and their secretions are essential to establish uterine receptivity and to mimic the internal in vivo environment.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135886983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitosis is vital for cell renewal and involves dynamic chromatin organization and nuclear architectural alternations. Regardless of these changes, some epigenetic marks/factors are inheritable throughout cell division. Over the years, it has been found that certain transcription factors remain bound to chromatin during the transcriptionally silent mitotic phase suggesting their potential role in transmitting regulatory information trans-generationally. This phenomenon is referred to as ‘genome bookmarking.’ In recent findings, a few Nuclear Receptors (NRs) have been reported to be associated with mitotic chromatin (constitutive, ligand-dependent, or partner-mediated manner). Recent studies from our lab have shown that diseaseassociated polymorphic variants of NRs severely impair the genome bookmarking phenomenon exhibited by the receptor. Vitamin D Receptor (VDR), a member of the NR superfamily, has both calcemic and non-calcemic functions, including but not limited to cell proliferation and differentiation, immune modulation, reproduction, and metabolism. Thus, its abnormal function can lead to diseases like osteoarthritis, bone disorders, cancer, HVDRR, diabetes, etc. According to a study from our laboratory, VDR participates in the transmission of cellular traits to progeny cells by constitutively interacting with mitotic chromatin. Additionally, it promotes the interaction of its heterodimeric partner RXR with mitotic chromatin. Furthermore, in another recent study, we evaluated the mechanism involved in the malfunctioning of disease-associated VDR-SNP variants at multiple regulatory levels. This study revealed that the 'genome bookmarking' property of VDR is severely impaired in several variants, both with and without its cognate ligand. Moreover, partner-mediated mitotic chromatin interaction of VDR-SNP variants was examined, with the results suggesting that partner RXR cannot rescue compromised or lost mitotic chromatin interaction. Based on these findings, small molecules termed ‘tweaker-ligands’ that can reorient aberrant receptor conformation towards the normal functional output could be designed or repurposed for disease management.
有丝分裂对细胞更新至关重要，涉及动态染色质组织和核结构的改变。不管这些变化，一些表观遗传标记/因子在细胞分裂过程中是可遗传的。多年来，人们发现某些转录因子在转录沉默的有丝分裂阶段仍然与染色质结合，这表明它们在跨代传递调控信息方面具有潜在作用。这种现象被称为“基因组书签”。在最近的研究中，一些核受体(nr)被报道与有丝分裂染色质相关(构成型、配体依赖性或伴侣介导方式)。我们实验室最近的研究表明，NRs的疾病相关多态性变异严重损害了受体所表现出的基因组书签现象。维生素D受体(Vitamin D Receptor, VDR)是NR超家族成员之一，具有钙化和非钙化功能，包括但不限于细胞增殖和分化、免疫调节、生殖和代谢。因此，其功能异常可导致骨关节炎、骨紊乱、癌症、HVDRR、糖尿病等疾病。根据我们实验室的一项研究，VDR通过与有丝分裂染色质的组成性相互作用参与细胞性状向后代细胞的传递。此外，它促进其异二聚体伙伴RXR与有丝分裂染色质的相互作用。此外，在最近的另一项研究中，我们评估了与疾病相关的VDR-SNP变异在多个调控水平上发生故障的机制。这项研究表明，VDR的“基因组书签”特性在几种变体中严重受损，无论是否有其同源配体。此外，研究了VDR-SNP变异的伴侣介导的有丝分裂染色质相互作用，结果表明伴侣RXR不能挽救受损或丢失的有丝分裂染色质相互作用。基于这些发现，被称为“微调配体”的小分子可以将异常的受体构象重新定向到正常的功能输出，可以设计或重新用于疾病管理。
{"title":"Disease-Associated SNP Variants of Vitamin D Receptor Exhibit Compromised Receptor Function and Genome Bookmarking Properties","authors":"Neha Kumari, Jyoti Kashyap, None Rakesh K. Tyagi","doi":"10.18311/jer/2023/34987","DOIUrl":"https://doi.org/10.18311/jer/2023/34987","url":null,"abstract":"Mitosis is vital for cell renewal and involves dynamic chromatin organization and nuclear architectural alternations. Regardless of these changes, some epigenetic marks/factors are inheritable throughout cell division. Over the years, it has been found that certain transcription factors remain bound to chromatin during the transcriptionally silent mitotic phase suggesting their potential role in transmitting regulatory information trans-generationally. This phenomenon is referred to as ‘genome bookmarking.’ In recent findings, a few Nuclear Receptors (NRs) have been reported to be associated with mitotic chromatin (constitutive, ligand-dependent, or partner-mediated manner). Recent studies from our lab have shown that diseaseassociated polymorphic variants of NRs severely impair the genome bookmarking phenomenon exhibited by the receptor. Vitamin D Receptor (VDR), a member of the NR superfamily, has both calcemic and non-calcemic functions, including but not limited to cell proliferation and differentiation, immune modulation, reproduction, and metabolism. Thus, its abnormal function can lead to diseases like osteoarthritis, bone disorders, cancer, HVDRR, diabetes, etc. According to a study from our laboratory, VDR participates in the transmission of cellular traits to progeny cells by constitutively interacting with mitotic chromatin. Additionally, it promotes the interaction of its heterodimeric partner RXR with mitotic chromatin. Furthermore, in another recent study, we evaluated the mechanism involved in the malfunctioning of disease-associated VDR-SNP variants at multiple regulatory levels. This study revealed that the 'genome bookmarking' property of VDR is severely impaired in several variants, both with and without its cognate ligand. Moreover, partner-mediated mitotic chromatin interaction of VDR-SNP variants was examined, with the results suggesting that partner RXR cannot rescue compromised or lost mitotic chromatin interaction. Based on these findings, small molecules termed ‘tweaker-ligands’ that can reorient aberrant receptor conformation towards the normal functional output could be designed or repurposed for disease management.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135886988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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