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1.
Reprod Biol Endocrinol ; 22(1): 82, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010074

RESUMO

BACKGROUND: Exploring the molecular mechanisms of primordial germ cell (PGC) migration and the involvement of gonadal somatic cells in gonad development is valuable for comprehending the origins and potential treatments of reproductive-related diseases. METHODS: Diaphanous related formin 1 (Diaph1, also known as mDia1) was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). Subsequently, the CRISPR-Cas9 technology was used to construct Diaph1 knockout mice to investigate the role of Diaph1 in gonad development. RESULTS: Based on data from public databases, a differentially expressed gene Diaph1, was identified in the migration of mouse PGC. Additionally, the number of PGCs was significantly reduced in Diaph1 knockout mice compared to wild type mice, and the expression levels of genes related to proliferation (Dicer1, Mcm9), adhesion (E-cadherin, Cdh1), and migration (Cxcr4, Hmgcr, Dazl) were significantly decreased. Diaph1 knockout also inhibited Leydig cell proliferation and induced apoptosis in the testis, as well as granulosa cell apoptosis in the ovary. Moreover, the sperm count in the epididymal region and the count of ovarian follicles were significantly reduced in Diaph1 knockout mice, resulting in decreased fertility, concomitant with lowered levels of serum testosterone and estradiol. Further research found that in Diaph1 knockout mice, the key enzymes involved in testosterone synthesis (CYP11A1, 3ß-HSD) were decreased in Leydig cells, and the estradiol-associated factor (FSH receptor, AMH) in granulosa cells were also downregulated. CONCLUSIONS: Overall, our findings indicate that the knockout of Diaph1 can disrupt the expression of factors that regulate sex hormone production, leading to impaired secretion of sex hormones, ultimately resulting in damage to reproductive function. These results provide a new perspective on the molecular mechanisms underlying PGC migration and gonadal development, and offer valuable insights for further research on the causes, diagnosis, and treatment of related diseases.


Assuntos
Proliferação de Células , Forminas , Células Germinativas , Gônadas , Camundongos Knockout , Animais , Camundongos , Feminino , Masculino , Forminas/genética , Forminas/metabolismo , Proliferação de Células/genética , Gônadas/metabolismo , Células Germinativas/metabolismo , Apoptose/genética , Testículo/metabolismo , Testículo/crescimento & desenvolvimento , Testículo/citologia , Movimento Celular/genética , Ovário/metabolismo , Ovário/crescimento & desenvolvimento , Camundongos Endogâmicos C57BL
2.
Front Immunol ; 15: 1389674, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994369

RESUMO

Cell death is an important process in the body, as it occurs throughout every tissue during development, disease, and tissue regeneration. Phagocytes are responsible for clearing away dying cells and are typically characterized as either professional or nonprofessional phagocytes. Professional phagocytes, such as macrophages, are found in nearly every part of the body while nonprofessional phagocytes, such as epithelial cells, are found in every tissue type. However, there are organs that are considered "immune-privileged" as they have little to no immune surveillance and rely on nonprofessional phagocytes to engulf dying cells. These organs are surrounded by barriers to protect the tissue from viruses, bacteria, and perhaps even immune cells. The Drosophila ovary is considered immune-privileged, however the presence of hemocytes, the macrophages of Drosophila, around the ovary suggests they may have a potential function. Here we analyze hemocyte localization and potential functions in response to starvation-induced cell death in the ovary. Hemocytes were found to accumulate in the oviduct in the vicinity of mature eggs and follicle cell debris. Genetic ablation of hemocytes revealed that the presence of hemocytes affects oogenesis and that they phagocytose ovarian cell debris and in their absence fecundity decreases. Unpaired3, an IL-6 like cytokine, was found to be required for the recruitment of hemocytes to the oviduct to clear away obsolete follicle cells. These findings demonstrate a role for hemocytes in the ovary, providing a more thorough understanding of phagocyte communication and cell clearance in a previously thought immune-privileged organ.


Assuntos
Hemócitos , Ovário , Fagócitos , Fagocitose , Animais , Feminino , Ovário/imunologia , Hemócitos/imunologia , Fagócitos/imunologia , Fagócitos/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/imunologia , Oogênese , Drosophila/imunologia
3.
Ecotoxicol Environ Saf ; 281: 116651, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38959790

RESUMO

Betamethasone has been extensively used in medicine in recent years and poses potential hazards to aquatic organisms. This study investigated the reproductive toxic effects of betamethasone exposure in fish, employing female Japanese medaka (Oryzias latipes) as a model. Betamethasone exposure at environmentally relevant concentrations (0, 20, 200, and 2000 ng/L) for a period of 15 weeks resulted in its high accumulation in the ovary, leading to abnormal oogenesis in female Japanese medaka. The production of gonadotropins (LH and FSH) in the pituitary gland was inhibited, and sex steroid biosynthesis in the ovary was significantly influenced at the transcriptional level. The imbalance of androgens and estrogens resulted in a decrease in the E2/T ratio and hepatic VTG synthesis, and the suppression of estrogen receptor signaling was also induced. Furthermore, betamethasone exposure delayed spawning and reduced fertility in the F0 generation, and had detrimental effects on the fertilization rate and hatchability of the F1 generation. Our results showed that environmental betamethasone had the potential to adversely affect female fertility and steroid hormone dynamics in fish.


Assuntos
Betametasona , Oryzias , Ovário , Reprodução , Poluentes Químicos da Água , Animais , Oryzias/fisiologia , Feminino , Betametasona/toxicidade , Poluentes Químicos da Água/toxicidade , Reprodução/efeitos dos fármacos , Ovário/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Exposição Ambiental , Hormônios Esteroides Gonadais
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 507-512, 2024 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-38948295

RESUMO

There is a global trend of declining fertility among people of childbearing age and mankind is confronted with great challenges of fertility problems. As a result, fertility preservation technology has emerged. Fertility preservation involves interventions and procedures aimed at preserving the patients' chances of having children when their fertility may have been impaired by their medical conditions or the treatments thereof, for example, chemotherapy and/or radiotherapy for cancer. The changes in patients' fertility can be temporary or permanent damage. Fertility preservation can help people diagnosed with cancer or other non-malignant diseases. More and more fertility preservation methods are being used to preserve the fertility of cancer patients and protect their reproductive organs from gonadotoxicity. Fertility preservation may be appropriate for young patients with early-stage cancers and good prognosis before they undergo treatments (chemotherapy and/or radiotherapy) that can negatively affect their fertility. It is also appropriate for patients with chronic conditions or those who have encountered environmental exposures that affect their gonadal function. Fertility preservation methods include oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation (OTC) for women and sperm freezing and testicular tissue freezing for men. The survival rates of children and adolescents diagnosed with malignant tumors have been steadily increasing as a result of advances in cancer treatments. Cryopreservation of oocytes and sperm is recognized as a well-established and successful strategy for fertility preservation in pubertal patients. OTC is the sole option for prepubertal girls. On the other hand, cryopreservation of immature testicular tissue remains the only alternative for prepubertal boys, but the technology is still in the experimental stage. A review showed that the utilization rate of cryopreserved semen ranged from 2.6% to 21.5%. In the case of cryopreserved female reproductive materials, the utilization rate ranged from 3.1% to 8.7% for oocytes, approximately from 9% to 22.4% for embryos, and from 6.9% to 30.3% for ovarian tissue. When patients have needs for fertility treatment, cryopreserved vitrified oocytes are resuscitated and in vitro fertilization-embryo transfer (IVF-ET) was performed to help patients accomplish their reproductive objectives, with the live birth rate (LBR) being 32%. On the other hand, when cryopreserved embryos are resuscitated and transferred, the LBR was 41%. OTC has the advantage of restoring natural fertility and presents a LBR of 33%, compared with the LBR of 19% among 266 IVF patients. In addition, OTC has the benefit of restoring the endocrine function. It has been observed that the shortest recovery time of the first menstruation after transplantation was 3.9 months, and the recovery rate of ovarian function reached 100%. To date, a growing number of cancer survivors and patients with other diseases are benefiting from fertility preservation measures. In the face of declining human fertility, fertility preservation provides a new approach to human reproduction. Fertility preservation should be applied in line with the ethical principles so as to fully protect the rights and interests of patients and their offsprings.


Assuntos
Criopreservação , Preservação da Fertilidade , Neoplasias , Feminino , Humanos , Masculino , Criopreservação/métodos , Preservação da Fertilidade/métodos , Oócitos , Ovário , Espermatozoides , Testículo
5.
Front Endocrinol (Lausanne) ; 15: 1417007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952389

RESUMO

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health.


Assuntos
Envelhecimento , Mitocôndrias , Ovário , Humanos , Feminino , Mitocôndrias/metabolismo , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Ovário/metabolismo , Ovário/fisiologia , Animais , Antioxidantes/uso terapêutico , Oócitos/metabolismo , Oócitos/fisiologia , Mitofagia/fisiologia
6.
Zhongguo Zhen Jiu ; 44(7): 821-30, 2024 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-38986596

RESUMO

OBJECTIVE: To observe the protective effect of acupuncture at "Zhibian" (BL 54) through "Shuidao (ST 28)" based on the PI3K/AKT/FOXO3a pathway in mice with poor ovarian response (POR), and to explore the possible mechanism of acupuncture in inhibiting ovarian granulosa cells apoptosis in POR. METHODS: A total of 45 mice with regular estrous cycles were randomly divided into a blank group, a model group and an acupuncture group, with 15 mice in each group. Mice in the model group and the acupuncture group were given triptolide suspension (50 mg•kg-1•d-1) by gavage for 2 weeks to establish POR model. After successful modeling, mice in the acupuncture group were given acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) for 2 weeks, once a day, 20 min each time. Ovulation induction was started the day after the intervention ended, and samples were taken from each group after ovulation induction. Vaginal smears were used to observe changes in the estrous cycle of mice. The number of oocytes retrieved, ovarian wet weight, final body weight, and ovarian index were measured. The levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) in serum were detected by ELISA. The morphology of ovarian tissue was observed by HE staining. The apoptosis of ovarian granulosa cells was detected by TUNEL staining. The mRNA expression of PI3K, AKT, and FOXO3a in ovarian tissue was detected by real-time fluorescence quantitative PCR. The protein expression of Bcl-2 associated X protein (BAX), caspase-3, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) in ovarian tissue was detected by Western blot. RESULTS: Compared with the blank group, the rate of estrous cycle disorder in the model group was increased (P<0.01); compared with the model group, the rate of estrous cycle disorder in the acupuncture group was decreased (P<0.01). Compared with the blank group, the number of oocytes retrieved, ovarian wet weight, ovarian index, and final body weight in the model group were decreased (P<0.01); compared with the model group, the number of oocytes retrieved, ovarian index, and ovarian wet weight were increased (P<0.01, P<0.05), and there was no significant difference in final body weight (P>0.05) in the acupuncture group. Compared with the blank group, the serum levels of FSH and LH were increased (P<0.01), and the serum levels of AMH and E2 were decreased (P<0.01) in the model group; compared with the model group, the serum levels of FSH and LH were decreased (P<0.01, P<0.05), and the serum levels of AMH and E2 were increased (P<0.01, P<0.05) in the acupuncture group. Compared with the blank group, the number of normal developing follicles in ovarian tissue in the model group was decreased and the morphology was poor, while the number of atretic follicles increased; compared with the model group, the number, morphology, and granulosa cell structure of follicles in the acupuncture group improved to varying degrees, and the number of atretic follicles decreased. Compared with the blank group, the apoptosis rate of ovarian granulosa cells in the model group was increased (P<0.01); compared with the model group, the apoptosis rate of ovarian granulosa cells in the acupuncture group was decreased (P<0.01). Compared with the blank group, the FOXO3a mRNA expression and caspase-3 and BAX protein expression in ovarian tissue in the model group were increased (P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were decreased (P<0.01); compared with the model group, the mRNA expression of FOXO3a and protein expression of caspase-3 and BAX in ovarian tissue in the acupuncture group were decreased (P<0.05, P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were increased (P<0.01, P<0.05). CONCLUSION: Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could inhibit ovarian cell apoptosis, and improve ovarian function in POR mice, and its mechanism may be related to the regulation of key factors in the PI3K/AKT/FOXO3a pathway.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Proteína Forkhead Box O3 , Ovário , Proteínas Proto-Oncogênicas c-akt , Animais , Feminino , Camundongos , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Ovário/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/genética , Apoptose , Ovulação
7.
J Ovarian Res ; 17(1): 139, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970048

RESUMO

Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the critical role of ovarian fibrosis in maintaining the normal physiological function of the mammalian ovaries, research on this condition has been greatly underestimated, which leads to a lack of clinical treatment options for ovarian dysfunction caused by fibrosis. This review synthesizes recent research on the molecular mechanisms of ovarian fibrosis, encompassing TGF-ß, extracellular matrix, inflammation, and other profibrotic factors contributing to abnormal ovarian fibrosis. Additionally, we summarize current treatment approaches for ovarian dysfunction targeting ovarian fibrosis, including antifibrotic drugs, stem cell transplantation, and exosomal therapies. The purpose of this review is to summarize the research progress on ovarian fibrosis and to propose potential therapeutic strategies targeting ovarian fibrosis for the treatment of ovarian dysfunction.


Assuntos
Fibrose , Ovário , Humanos , Feminino , Ovário/patologia , Ovário/metabolismo , Animais , Matriz Extracelular/metabolismo , Doenças Ovarianas/metabolismo , Doenças Ovarianas/patologia , Doenças Ovarianas/terapia , Terapia de Alvo Molecular , Fator de Crescimento Transformador beta/metabolismo
8.
Sci Data ; 11(1): 777, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003290

RESUMO

The ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat's sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.


Assuntos
Cabras , Ovário , Maturidade Sexual , Transcriptoma , Útero , Animais , Feminino , Cabras/genética , Cabras/metabolismo , Útero/metabolismo , Ovário/metabolismo , Ovário/crescimento & desenvolvimento , Metaboloma , Metabolômica
9.
J Ovarian Res ; 17(1): 141, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982490

RESUMO

INTRODUCTION: Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. METHODS: Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn't survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. RESULTS: cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. CONCLUSION: The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Camundongos Knockout , Placenta , Insuficiência Ovariana Primária , Animais , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Feminino , Camundongos , Gravidez , Placenta/metabolismo , Ovário/metabolismo , Ovário/patologia , Modelos Animais de Doenças , Oócitos/metabolismo
10.
Elife ; 132024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985571

RESUMO

Diaphorina citri serves as the primary vector for 'Candidatus Liberibacter asiaticus (CLas),' the bacterium associated with the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response to CLas infection in D. citri. Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and CLas titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3' untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and CLas titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant (DcMet), and the transcription factor, Krüppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like (DcVg-1-like), vitellogenin A1-like (DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result, CLas hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of CLas, suggesting a mutualistic interaction between CLas and D. citri ovaries.


Assuntos
Fertilidade , Hemípteros , Hormônios de Inseto , Ácido Pirrolidonocarboxílico , Transdução de Sinais , Animais , Hormônios de Inseto/metabolismo , Hormônios de Inseto/genética , Feminino , Hemípteros/microbiologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/metabolismo , Rhizobiaceae/fisiologia , Rhizobiaceae/metabolismo , Metabolismo dos Lipídeos , Ovário/microbiologia , Ovário/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Hormônios Juvenis/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Liberibacter , Oligopeptídeos
11.
Biol Direct ; 19(1): 52, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956667

RESUMO

BACKGROUND: Adiposity profoundly impacts reproductive health in both humans and animals. However, the precise subpopulations contributing to infertility under obese conditions remain elusive. RESULTS: In this study, we established an obese mouse model through an eighteen-week high-fat diet regimen in adult female mice. Employing single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive single-cell atlas of ovarian tissues from these mice to scrutinize the impact of obesity on the ovarian microenvironment. ScRNA-seq revealed notable alterations in the microenvironment of ovarian tissues in obese mice. Granulosa cells, stromal cells, T cells, and macrophages exhibited functional imbalances compared to the control group. We observed heightened interaction strength in the SPP1-CD44 pairing within lgfbp7+ granulosa cell subtypes and Il1bhigh monocyte subtypes in the ovarian tissues of obese mice. Moreover, the interaction strength between Il1bhigh monocyte subtypes and Pdgfrb+ stromal cell subtypes in the form of TNF - TNFrsf1α interaction was also enhanced subsequently to obesity, potentially contributing to ovarian fibrosis pathogenesis. CONCLUSIONS: We propose a model wherein granulosa cells secrete SPP1 to activate monocytes, subsequently triggering TNF-α secretion by monocytes, thereby activating stromal cells and ultimately leading to the development of ovarian fibrosis. Intervening in this process may represent a promising avenue for improving clinical outcomes in fertility treatments for obese women.


Assuntos
Fibrose , Camundongos Obesos , Obesidade , Análise de Célula Única , Animais , Feminino , Camundongos , Fibrose/genética , Obesidade/genética , Obesidade/metabolismo , Perfilação da Expressão Gênica , Ovário/metabolismo , Transcriptoma , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Células da Granulosa/metabolismo
12.
Clin Transl Sci ; 17(7): e13863, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38955776

RESUMO

Ovaries play a crucial role in the regulation of numerous essential processes that occur within the intricate framework of female physiology. They are entrusted with the responsibility of both generating a new life and orchestrating a delicate hormonal symphony. Understanding their functioning is crucial for gaining insight into the complexities of reproduction, health, and fertility. In addition, ovaries secrete hormones that are crucial for both secondary sexual characteristics and the maintenance of overall health. A three-dimensional (3D) prosthetic ovary has the potential to restore ovarian function and preserve fertility in younger females who have undergone ovariectomies or are afflicted with ovarian malfunction. Clinical studies have not yet commenced, and the production of 3D ovarian tissue for human implantation is still in the research phase. The main challenges faced while creating a 3D ovary for in vivo implantation include sustenance of ovarian follicles, achieving vascular infiltration into the host tissue, and restoring hormone circulation. The complex ovarian microenvironment that is compartmentalized and rigid makes the biomimicking of the 3D ovary challenging in terms of biomaterial selection and bioink composition. The successful restoration of these properties in animal models has led to expectations for the development of human ovaries for implantation. This review article summarizes and evaluates the optimal 3D models of ovarian structures and their safety and efficacy concerns to provide concrete suggestions for future research.


Assuntos
Ovário , Impressão Tridimensional , Feminino , Humanos , Ovário/fisiologia , Animais , Engenharia Tecidual/métodos , Fertilidade , Preservação da Fertilidade/métodos , Alicerces Teciduais/química
13.
Science ; 385(6704): 15, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38963833

RESUMO

Studies find long-lived proteins are prevalent in the organs.


Assuntos
Oócitos , Ovário , Proteínas , Animais , Feminino , Humanos , Camundongos , Ovário/metabolismo , Proteínas/metabolismo , Proteínas/química , Oócitos/metabolismo
14.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000423

RESUMO

Methyl farnesoate epoxidase (MFE) is a gene encoding an enzyme related to the last step of juvenile hormone biosynthesis. Mn-MFE cDNA has a total length of 1695 bp and an open reading frame (ORF) length of 1482 bp, encoding 493 amino acids. Sequence analysis showed that its amino acid sequence has a PPGP hinge, an FGCG structural domain, and other structural domains specific to the P450 family of enzymes. Mn-MFE was most highly expressed in the hepatopancreas, followed by the ovary and gill, weakly expressed in heart and muscle tissue, and barely expressed in the eyestalk and cranial ganglion. Mn-MFE expression remained stable during the larval period, during which it mainly played a critical role in gonadal differentiation. Expression in the ovary was positively correlated and expression in the hepatopancreas was negatively correlated with ovarian development. In situ hybridization (ISH) showed that the signal was expressed in the oocyte, nucleus, cell membrane and follicular cells, and the intensity of expression was strongest at stage O-IV. The knockdown of Mn-MFE resulted in a significantly lower gonadosomatic index and percentage of ovaries past stage O-III compared to the control group. However, no differences were found in the cumulative frequency of molting between the experimental and control groups. Moreover, the analysis of ovarian tissue sections at the end of the experiment showed differences between groups in development speed but not in subcellular structure. These results demonstrate that Mn-MFE promotes the ovarian development of Macrobrachium nipponense adults but has no effect on molting.


Assuntos
Ovário , Palaemonidae , Animais , Ovário/metabolismo , Ovário/crescimento & desenvolvimento , Feminino , Palaemonidae/genética , Palaemonidae/crescimento & desenvolvimento , Palaemonidae/enzimologia , Palaemonidae/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Sequência de Aminoácidos , Filogenia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Hepatopâncreas/metabolismo , Hepatopâncreas/crescimento & desenvolvimento , Ácidos Graxos Insaturados
15.
Curr Gene Ther ; 24(5): 347-355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005061

RESUMO

Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary. It also mediates somatic cell proliferation and steroidogenesis, thereby affecting spermatogenesis in males. In addition to its physiological effects on the reproductive system, HGF has shown advantages in preclinical studies over recent years for the treatment of male and female infertility, particularly in women with premature ovarian insufficiency. This review aims to summarize the pleiotropic functions of HGF in the reproductive system and to provide prospects for its clinical application.


Assuntos
Fator de Crescimento de Hepatócito , Humanos , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Feminino , Masculino , Reprodução/genética , Animais , Ovário/metabolismo , Espermatogênese , Testículo/metabolismo , Células da Granulosa/metabolismo
16.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000181

RESUMO

Perimenopause significantly impacts women's health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing ex vivo methodologies, ovarian cortex specimens from perimenopausal women were treated with exosomes derived from human umbilical cord mesenchymal stem cells and cultured under specific conditions (patent number: PCT/US2022/073467). The exosomes were produced under cyclic guanosine monophosphate (cGMP) conditions, ensuring high safety standards. Estrogen levels were quantified using enzyme-linked immunosorbent assay (ELISA), and gene expression changes in estrogen and follicle-stimulating hormone (FSH) receptors were assessed via quantitative polymerase chain reaction (PCR). Immunohistochemistry (IHC) was utilized to evaluate cellular proliferation and apoptotic markers. The results indicated a significant increase in estrogen levels and estrogen receptor-alpha (Erα) expression in treated tissues compared to controls. Additionally, a decrease in apoptotic markers and an increase in cellular proliferation markers were observed. These findings suggest that exosome therapy can effectively enhance estrogen production and modulate receptor sensitivity in perimenopausal ovarian tissues. This approach could serve as a safer alternative to HRT, aligning with the body's natural regulatory mechanisms and potentially offering a more effective treatment option for managing perimenopausal symptoms.


Assuntos
Estrogênios , Exossomos , Perimenopausa , Humanos , Exossomos/metabolismo , Feminino , Perimenopausa/metabolismo , Estrogênios/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Proliferação de Células , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Pessoa de Meia-Idade , Apoptose , Receptores do FSH/metabolismo , Receptores do FSH/genética , Ovário/metabolismo
17.
J Med Food ; 27(7): 651-660, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38975681

RESUMO

Purpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNFα], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1ß], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNFα, COX-2, IL-1ß, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants.


Assuntos
Apoptose , Compostos Benzidrílicos , Dano ao DNA , Disruptores Endócrinos , Ácido Gálico , Ovário , Estresse Oxidativo , Fenóis , Animais , Feminino , Ácido Gálico/farmacologia , Compostos Benzidrílicos/toxicidade , Ovário/efeitos dos fármacos , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Ratos , Dano ao DNA/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Substâncias Protetoras/farmacologia , Hormônio Luteinizante/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Ratos Sprague-Dawley , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Progesterona , Humanos , Antioxidantes/farmacologia , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo
18.
Diagn. tratamento ; 29(2): 81-5, abr-jun. 2024. tab
Artigo em Português | LILACS, Sec. Est. Saúde SP | ID: biblio-1553900

RESUMO

Contexto: Luteoma é neoplasia rara e benigna do ovário, específica da gravidez. Considera-se que seja causada por efeitos hormonais, principalmente da gonadotrofina coriônica. Objetivo: Analisar artigos selecionados sobre luteoma da gravidez e realizar revisão bibliográfica a partir dessas publicações. Desenho: A busca dos artigos foi realizada por meio da plataforma PubMed. Procedeu-se uma busca aos descritores da doença e seu correspondente em inglês (luteoma) no portal da BVSalud. Métodos: Consistiu em revisão bibliográfica, onde foram utilizados artigos publicados de 1972 até 2022. Resultados: A origem celular dos luteomas ainda é desconhecida, mas considera-se que tal processo ocorra devido a uma reação hiperplásica à gravidez, visto que o efeito de virilização regride após o parto. Discussão: Sendo pouco diagnosticado, tendo menos de 200 casos reportados, são geralmente achados durante parto cesáreo ou durante ligadura tubária no pós-parto. Seu aparecimento está relacionado a fatores hormonais da gravidez e hiperplasia ocasionada pela luteinização das células estromais. Os efeitos do luteoma gravídico no organismo estão relacionados, além da virilização da paciente e do feto, com o surgimento da síndrome do ovário policístico e diabetes. Conclusões: Tendo baixa incidência, o luteoma gravídico pode se apresentar como desafio para seu diagnóstico adequado. O diagnóstico precoce permitirá o tratamento adequado, evitando-se efeitos indesejáveis, virilizantes, para a gestante e para o nascituro. É fundamental o preparo dos profissionais de saúde para o diagnóstico e tratamento do luteoma gravídico.


Assuntos
Ovário , Luteoma , Neoplasias , Transtornos do Desenvolvimento Sexual , Hiperandrogenismo
19.
J Obstet Gynaecol ; 44(1): 2362416, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38847083

RESUMO

BACKGROUND: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. METHODS: Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. RESULTS: Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. CONCLUSION: The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.


With advancements in science and technology, ovarian transplantation techniques have become increasingly mature. However, there are still many questions that need to be addressed. For instance, the large size of the transplanted ovarian tissues may cause over-recruitment of the primordial follicles. When the transplanted ovarian tissue is too small, it can only exert limited functionality and may not meet the patient's needs. This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function in rats after oophorectomy, and to provide a theoretical basis for determining the minimum effective volume of heterotopic ovarian tissue transplantation.


Assuntos
Ciclo Estral , Ovariectomia , Ovário , Transplante Heterotópico , Animais , Feminino , Ovário/transplante , Ratos , Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/sangue , Estradiol/sangue , Ratos Sprague-Dawley , Tamanho do Órgão , Folículo Ovariano , Reprodução/fisiologia
20.
J Ovarian Res ; 17(1): 122, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844959

RESUMO

INTRODUCTION: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.


Assuntos
Metilação de DNA , Endométrio , Cistos Ovarianos , Ovário , Feminino , Humanos , Cistos Ovarianos/genética , Cistos Ovarianos/patologia , Cistos Ovarianos/metabolismo , Endométrio/metabolismo , Endométrio/patologia , Adulto , Ovário/metabolismo , Ovário/patologia , Endometriose/genética , Endometriose/patologia , Endometriose/metabolismo , Epigênese Genética
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