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1.
Sci Data ; 11(1): 383, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615064

RESUMO

The rete ovarii (RO) is an epithelial structure that arises during development in close proximity to the ovary and persists throughout adulthood. However, the functional significance of the RO remains elusive, and it is absent from recent discussions of female reproductive anatomy. The RO comprises three regions: the intraovarian rete within the ovary, the extraovarian rete in the periovarian tissue, and the connecting rete linking the two. We hypothesize that the RO plays a pivotal role in ovarian homeostasis and responses to physiological changes. To begin to uncover the nature and function of RO cells, we conducted transcriptomic profiling of the RO. This study presents three datasets, and reports our analysis and quality control approaches for bulk, single-cell, and nucleus-level transcriptomics of the fetal and adult RO tissues using the Pax8-rtTA; Tre-H2B-GFP mouse line, where all RO regions express nuclear GFP. The integration and rigorous validation of these datasets will advance our understanding of the RO's roles in ovarian development, female maturation, and adult female fertility.


Assuntos
Ovário , Transcriptoma , Animais , Feminino , Camundongos , Feto , Perfilação da Expressão Gênica , Ovário/embriologia , Ovário/crescimento & desenvolvimento
2.
Science ; 382(6670): 600-606, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37917714

RESUMO

Sex determination in mammals depends on the differentiation of the supporting lineage of the gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although the Y-linked testis-determining gene Sry has been identified, the ovarian-determining factor remains unknown. In this study, we identified -KTS, a major, alternatively spliced isoform of the Wilms tumor suppressor WT1, as a key determinant of female sex determination. Loss of -KTS variants blocked gonadal differentiation in mice, whereas increased expression, as found in Frasier syndrome, induced precocious differentiation of ovaries independently of their genetic sex. In XY embryos, this antagonized Sry expression, resulting in male-to-female sex reversal. Our results identify -KTS as an ovarian-determining factor and demonstrate that its time of activation is critical in gonadal sex differentiation.


Assuntos
Ovário , Processos de Determinação Sexual , Proteínas WT1 , Animais , Feminino , Masculino , Camundongos , Ovário/crescimento & desenvolvimento , Processos de Determinação Sexual/genética , Proteína da Região Y Determinante do Sexo/genética , Proteína da Região Y Determinante do Sexo/metabolismo , Testículo/crescimento & desenvolvimento , Proteínas WT1/genética , Proteínas WT1/metabolismo , Isoformas de Proteínas
3.
Hum Reprod Update ; 29(4): 434-456, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-36857094

RESUMO

BACKGROUND: Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction. OBJECTIVE AND RATIONALE: Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life. SEARCH METHODS: Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes. OUTCOMES: Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress). WIDER IMPLICATIONS: Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.


Assuntos
Oócitos , Ovário , Morte Celular Regulada , Adulto , Animais , Feminino , Humanos , Apoptose/fisiologia , Células da Granulosa/metabolismo , Células da Granulosa/fisiologia , Mamíferos/crescimento & desenvolvimento , Mamíferos/fisiologia , Oócitos/crescimento & desenvolvimento , Oócitos/fisiologia , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/fisiologia , Ovário/crescimento & desenvolvimento , Ovário/fisiologia , Morte Celular Regulada/fisiologia , Homeostase/fisiologia
4.
J Exp Zool B Mol Dev Evol ; 340(1): 18-33, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35167178

RESUMO

Insects are the dominant group of animals on Earth. Despite this abundance, most of our knowledge about many aspects of their biology and development come from a unique model, the vinegar fly, Drosophila melanogaster. Nevertheless, in the last years, the advances in molecular tools and imaging techniques have allowed the emergence of new insect models, adding valuable information to decipher the morphogenetic bases behind the formation and evolution of the vast diversity of shapes, sizes, and patterns that characterize them. Earwigs belong to Dermaptera which is a small order clustered in the Polyneopteran group. They are hemimetabolous insects with a flattened body, characteristic abdominal pincers, and maternal care behavior. This last feature and their role in agroecosystems have been studied in cosmopolitan species such as Forficula auricularia and Euborellia annulipes; however, their reproduction and embryonic development have been poorly addressed in laboratory conditions. In response, here we describe the ring-legged earwig Euborellia annulipes embryogenesis and life cycle from nymphal to adult stages, its reproduction, and essential morphological and behavioral characters. Additionally, using confocal and transmission electron microscopy we analyzed in detail the morphogenesis of its peculiar meroistic polytrophic ovary. Our aim is to provide an emerging model system to perform comparative studies on insect oogenesis, development, and morphological evolution.


Assuntos
Insetos , Modelos Animais , Oogênese , Animais , Feminino , Drosophila melanogaster , Ninfa , Ovário/crescimento & desenvolvimento
5.
Differentiation ; 129: 37-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36347737

RESUMO

A definition of normal human fetal and early postnatal ovarian development is critical to the ability to accurately diagnose the presence or absence of functional ovarian tissue in clinical specimens. Through assembling an extensive histologic and immunohistochemical developmental ontogeny of human ovarian specimens from 8 weeks of gestation through 16 years of postnatal, we present a comprehensive immunohistochemical mapping of normal protein expression patterns in the early fetal through post-pubertal human ovary and detail a specific expression-based definition of the early stages of follicular development. Normal fetal and postnatal ovarian tissue is defined by the presence of follicular structures and characteristic immunohistochemical staining patterns, including granulosa cells expressing Forkhead Box Protein L2 (FOXL2). However, the current standard array of immunohistochemical markers poorly defines ovarian stromal tissue, and additional work is needed to identify new markers to advance our ability to accurately identify ovarian stromal components in gonadal specimens from patients with disorders of sexual differentiation.


Assuntos
Folículo Ovariano , Ovário , Feminino , Humanos , Antígenos de Diferenciação/metabolismo , Diferenciação Celular , Células da Granulosa/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento
6.
Science ; 377(6610): 1092-1099, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36048960

RESUMO

In most organisms, reproduction is correlated with shorter life span. However, the reproductive queen in eusocial insects exhibits a much longer life span than that of workers. In Harpegnathos ants, when the queen dies, workers can undergo an adult caste switch to reproductive pseudo-queens (gamergates), exhibiting a five-times prolonged life span. To explore the relation between reproduction and longevity, we compared gene expression during caste switching. Insulin expression is increased in the gamergate brain that correlates with increased lipid synthesis and production of vitellogenin in the fat body, both transported to the egg. This results from activation of the mitogen-activated protein kinase (MAPK) branch of the insulin signaling pathway. By contrast, the production in the gamergate developing ovary of anti-insulin Imp-L2 leads to decreased signaling of the AKT/forkhead box O (FOXO) branch in the fat body, which is consistent with their extended longevity.


Assuntos
Formigas , Insulina , Longevidade , Reprodução , Animais , Formigas/metabolismo , Feminino , Insulina/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ovário/crescimento & desenvolvimento , Transdução de Sinais , Vitelogeninas/biossíntese
7.
Science ; 376(6599): eabh3104, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35549308

RESUMO

A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the "zygotene chromosomal bouquet." Here, we identified the "zygotene cilium" in oocytes. This cilium provides a cable system for the bouquet machinery and extends throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, oogenesis, ovarian development, and fertility. Thus, a cilium represents a conserved player in zebrafish and mouse meiosis, which sheds light on reproductive aspects in ciliopathies and suggests that cilia can control chromosomal dynamics.


Assuntos
Pareamento Cromossômico , Cílios , Oócitos , Oogênese , Ovário , Animais , Centrômero/genética , Centrômero/fisiologia , Pareamento Cromossômico/genética , Pareamento Cromossômico/fisiologia , Cílios/fisiologia , Feminino , Fertilidade/fisiologia , Camundongos , Morfogênese , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Oogênese/fisiologia , Ovário/crescimento & desenvolvimento , Telômero/genética , Telômero/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia
8.
Gene ; 823: 146393, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35248662

RESUMO

The Atlantic salmon (Salmo salar) is a globally important species for its value in fisheries and aquaculture, and as a research model. In order to characterise aspects of sex differentiation at the morphological and mRNA level in this species, the present study examined developmental changes in gonad morphology and gene expression in males and females between 0 and 79 days post hatch (dph). Morphological differentiation of the ovary (indicated by the formation of germ cell cysts) became apparent from 52 dph. By 79 dph, ovarian phenotype was evident in 100% of genotypic females. Testes remained in an undifferentiated-like state throughout the experiment, containing germ cells dispersed singularly within the gonadal region distal to the mesentery. There were no significant sex-related differences in gonad cross-section size, germ cell number or germ cell diameter during the experiment. The expression of genes involved in teleost sex differentiation (anti-müllerian hormone (amh), cytochrome P450, family 19, subfamily A, polypeptide 1a (cyp19a1a), forkhead box L2a (foxl2a), gonadal soma-derived factor (gsdf), r-spondin 1 (rspo1), sexually dimorphic on the Y chromosome (sdY)), retinoic acid-signalling (aldehyde dehydrogenase 1a2 (aldh1a2), cytochrome P450 family 26 a1 (cyp26a1), cytochrome P450 family 26 b1 (cyp26b1), t-box transcription factor 1 (tbx1a)) and neuroestrogen production (cytochrome P450, family 19, subfamily A, polypeptide 1b (cyp19a1b)) was investigated. Significant sex-related differences were observed only for the expression of amh, cyp19a1a, gsdf and sdY. In males, amh, gsdf and sdY were upregulated from 34, 59 and 44 dph respectively. In females, cyp19a1a was upregulated from 66 dph. Independent of sex, foxl2a expression was highest at 0 dph and had reduced âˆ¼ 47-fold by the time of morphological sex differentiation at 52 dph. This study provides new insights into the timing and sequence of some physiological changes associated with sex differentiation in Atlantic salmon. These findings also reveal that some aspects of the mRNA sex differentiation pathways in Atlantic salmon are unique compared to other teleost fishes, including other salmonids.


Assuntos
Proteínas de Peixes/genética , Ovário/crescimento & desenvolvimento , Salmo salar/crescimento & desenvolvimento , Testículo/crescimento & desenvolvimento , Animais , Feminino , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Ovário/química , Salmo salar/genética , Diferenciação Sexual , Transdução de Sinais , Testículo/química
9.
Int J Mol Sci ; 23(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163119

RESUMO

Juvenile hormone and ecdysone are key regulators in the metamorphosis and development. Grocho (Gro) is a highly conserved protein required for metamorphosis and development. Brown planthopper (Nilaparvata lugens) is a major pest affecting rice production in China and many Asian countries. Although the molecular function of Gro has been investigated in holometabolous insects such as Aedes aegypti and Drosophila melanogaster, their role in the hemimetabolous insect, brown planthopper, and the relationship between NlGro/NlGro1-L and JH/ecdysone signaling pathway, remained unknown. In this study, NlGroucho (NlGro) and NlGroucho1-like (NlGro1-L) were cloned. An analysis of the predicted protein sequence showed that NlGro has highly conserved Q domain and WD40 domain, and NlGro1-L has a highly conserved WD40 domain. The expression profiles of both genes were studied by quantitative real-time PCR (qRT-PCR). Their relative expressions were high in egg, head, wing, ovary, and testis. NlGro and NlGro1-L were found to interact genetically with juvenile hormone and ecdysone signaling by hormone treatment and RNAi of JH/ecdysone signaling-related genes. Moreover, when NlGro or NlGro1-L was down-regulated alone, the survival rate was decreased, the ovarian development was delayed, and the oviposition was also affected. All defects were aggravated when NlGro and NlGro1-L were down-regulated together. This study will help to develop new pesticides on the basis of the function of NlGro and NlGro1-L, and provide new possibilities for the control of Nilaparvata lugens.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hemípteros/crescimento & desenvolvimento , Proteínas de Insetos/metabolismo , Hormônios Juvenis/farmacologia , Metamorfose Biológica , Ovário/crescimento & desenvolvimento , Sequência de Aminoácidos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Feminino , Hemípteros/efeitos dos fármacos , Hemípteros/genética , Hemípteros/metabolismo , Proteínas de Insetos/genética , Ovário/efeitos dos fármacos , Ovário/metabolismo , Oviposição , Homologia de Sequência , Asas de Animais/efeitos dos fármacos , Asas de Animais/crescimento & desenvolvimento
10.
J Ovarian Res ; 15(1): 14, 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35067219

RESUMO

BACKGROUND: Ginseng is a powerful phytoestrogen with high antioxidant properties. OBJECTIVE: This study aimed to evaluate the effect of Panax Ginseng (PG) on folliculogenesis, proliferation, and apoptosis in the ovary impaired by nicotine. METHODS: Forty adult mice were divided into five groups. Control, sham, and nicotine groups, and co-treated groups of nicotine and ginseng in doses of 0.5 and 1 g/kg. Folliculogenesis was assessed via histopathology and serum evaluation of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) by ELISA. Lipid peroxidation and antioxidant enzyme activities both in homogenate tissue and serum were assayed by colorimetric analysis. Apoptotic markers of cytochrome c (Cyt c), Bax, and Bcl-2 were evaluated by RT-PCR. Proliferative index was studied by the Ki-67 immunostaining procedure. RESULTS: In comparison to the control or sham groups, nicotine significantly reduced the levels of FSH, LH, and estradiol hormones. An insignificant reduction was observed in the progesterone hormone. Nicotine reduced all healthy follicle numbers, except primordial (P = 0.001). Malondialdehyde (MDA) was increased in tissue and serum in the nicotine group (P = 0.01). Serum catalase (CAT) and enzymatic activity of superoxide dismutase (SOD) both were reduced in tissue and the serum, in the nicotine group. Nicotine induced a reduction in the proliferative indexes of granulosa and theca cells in pre-antral and antral follicles (P = 0.001). However, its effect on the proliferative index of stroma cells was not significant. Apoptotic markers were elevated in the nicotine group (P = 0.001). Co-treatment with ginseng elevated all sex hormones, increased healthy follicles, and reduced tissue or serum lipid peroxidation, compared with the nicotine group (p < 0.05). Co-Treatment with ginseng also reduced the expression of apoptotic markers and increased the proliferative indexes in granulosa and theca cells in pre-antral and antral follicles and also in stroma cells, in comparison to the nicotine group (P = 0.001). All above-mentioned alterations following treatment with ginseng were remarkable, especially in the dose of 1 g/kg. CONCLUSION: This study showed ginseng protects folliculogenesis via alteration of hypothalamic- pituitary-gonadal (HPG) axis, induction of proliferation in ovarian somatic cells, reduction of lipid peroxidation, and downregulation of apoptotic markers in the mouse ovary, treated with nicotine.


Assuntos
Nicotina/farmacologia , Ovário/efeitos dos fármacos , Panax , Preparações de Plantas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Catalase/sangue , Catalase/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Hormônios/sangue , Antígeno Ki-67/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/sangue , Camundongos , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
11.
Biochem Biophys Res Commun ; 589: 100-106, 2022 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-34902745

RESUMO

Many temperate ectotherms survive winter by entering diapause - a state of developmental (or reproductive) suppression or arrest - in response to short autumnal day lengths. Day lengths are assessed by the circadian clock, the biological time-keeping system that governs biological rhythms with a period of approximately 24 h. However, clock output molecules controlling this photoperiodic response are largely unknown for many insects. To identify these molecules in Hemiptera, we performed RNAi knockdowns of several candidate genes in the bean bug Riptortus pedestris to determine whether their silencing affects photoperiodic regulation of ovarian development (reproductive diapause). Knockdown of diuretic hormone 31, short neuropeptide F, neuropeptide F, ion transport peptide, neuropeptide-like precursor 1, and choline acetyltransferase had no effect on ovarian development and were therefore ruled out as regulators of the photoperiodic response. However, knockdown of vesicular glutamate transporter promoted ovarian development under diapause-inducing short days, and this is the first report of the functional involvement of glutamate signalling in insect photoperiodism. Improved knockdown of this transporter (or receptor) and RNAi of other genes involved in glutamate signal transduction is required to verify its role as an output of the circadian clock.


Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Relógios Circadianos/fisiologia , Heterópteros/fisiologia , Proteínas de Insetos/metabolismo , Fotoperíodo , Sistema X-AG de Transporte de Aminoácidos/genética , Animais , Relógios Circadianos/genética , Feminino , Regulação da Expressão Gênica , Heterópteros/genética , Proteínas de Insetos/genética , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Interferência de RNA , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo
12.
Arch Insect Biochem Physiol ; 109(1): e21854, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34783381

RESUMO

Cytorhinus lividipennis is a natural enemy of rice planthoppers and leafhoppers. Improving the fecundity of C. lividipennis will be helpful to improve its control effect on pests. However, little is known about the hormonal regulatory mechanism of reproduction in C. lividipennis. In the current study, we examined the role of 20-hydroxyecdysone (20E) biosynthesis relative gene Shadow in the reproduction of C. lividipennis. The complementary DNA sequence of ClSad is 2018 -bp in length with an open reading frame of 1398-bp encoding 465 amino acid residues. ClSad was readily detected in nymphal and adult stages, and highly expressed in the adult stage. ClSad was highly expressed in the midgut and ovaries of adult females. Moreover, RNA interference-mediated knockdown of ClSad reduced the 20E titers and ClVg transcript level, resulting in fewer fully developed eggs and a decrease in the number of eggs laid by dsSad-injected adult females within 15 days. These results suggest that ClSad plays a critical role in the reproduction of C. lividipennis. The present study provides insights into the molecular mechanism of the ClSad gene for the reproduction of C. lividipennis.


Assuntos
Ecdisterona/genética , Fertilidade/genética , Heterópteros/genética , Animais , Ecdisterona/biossíntese , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Heterópteros/metabolismo , Masculino , Ovário/crescimento & desenvolvimento , Interferência de RNA , Análise de Sequência de DNA
13.
Gene ; 809: 146023, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34673205

RESUMO

Steroidogenic factor 1 (sf1) (officially designated as nuclear receptor subfamily 5 group A member 1 [NR5A1]) is an important regulator of gonad development. Previous studies on sf1 in fish have been limited to cloning and in vitro expression experiments. In this study, we used antisense RNA to down-regulate sf1 transcription and sf1 protein expression. Down-regulation of sf1 resulted in an increase in body weight and inhibition of gonadal development in both males and females with the consequent lower gonadosomatic index compared to fish in the control group. Hematoxylin-eosin staining of the gonads of fish with down-regulated sf1 revealed fewer seminiferous tubules and sperm in the testis of males. In addition, the oocytes were mainly stage II and many of them were atretic follicle. We conducted comparative transcriptome and proteome analyses between the sf1-down-regulated group and the control group. These analyses revealed multiple gene-protein pairs and pathways involved in regulating the observed changes, including 44 and 74 differently expressed genes and proteins in males and females, respectively. The results indicated that dysfunctional retinal metabolism and fatty acid metabolism could be causes of the observed weight gain and gonad abnormalities in sf1-down-regulated fish. These findings demonstrate the feasibility of using antisense RNA for gene editing in fish. This methodology allows the study gene function in species less amenable to gene editing as for example aquaculture species with long life cycles.


Assuntos
Peso Corporal/genética , Ciclídeos/genética , Ovário/crescimento & desenvolvimento , Fator Esteroidogênico 1/genética , Testículo/crescimento & desenvolvimento , Animais , Aquicultura , Ciclídeos/crescimento & desenvolvimento , Regulação para Baixo , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Masculino , RNA Antissenso , Fator Esteroidogênico 1/metabolismo , Transfecção
14.
J Clin Endocrinol Metab ; 107(1): e254-e263, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34402903

RESUMO

BACKGROUND: Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. A genetic cause for POI can be found in up to 30% of women, elucidating key roles for these genes in human ovary development. OBJECTIVE: We aimed to identify the genetic mechanism underlying early-onset POI in 2 sisters from a consanguineous pedigree. METHODS: Genome sequencing and variant filtering using an autosomal recessive model was performed in the 2 affected sisters and their unaffected family members. Quantitative reverse transcriptase PCR (qRT-PCR) and RNA sequencing were used to study the expression of key genes at critical stages of human fetal gonad development (Carnegie Stage 22/23, 9 weeks post conception (wpc), 11 wpc, 15/16 wpc, 19/20 wpc) and in adult tissue. RESULTS: Only 1 homozygous variant cosegregating with the POI phenotype was found: a single nucleotide substitution in zinc finger SWIM-type containing 7 (ZSWIM7), NM_001042697.2: c.173C > G; resulting in predicted loss-of-function p.(Ser58*). qRT-PCR demonstrated higher expression of ZSWIM7 in the 15/16 wpc ovary compared with testis, corresponding to peak meiosis in the fetal ovary. RNA sequencing of fetal gonad samples showed that ZSWIM7 has a similar temporal expression profile in the developing ovary to other homologous recombination genes. MAIN CONCLUSIONS: Disruption of ZSWIM7 is associated with POI in humans. ZSWIM7 is likely to be important for human homologous recombination; these findings expand the range of genes associated with POI in women.


Assuntos
Amenorreia/genética , Proteínas de Ligação a DNA/genética , Meiose/genética , Oogênese/genética , Insuficiência Ovariana Primária/genética , Adolescente , Amenorreia/diagnóstico , Criança , Análise Mutacional de DNA , Feminino , Humanos , Mutação com Perda de Função , Ovário/crescimento & desenvolvimento , Linhagem , Mutação Puntual , Insuficiência Ovariana Primária/complicações , Insuficiência Ovariana Primária/diagnóstico , RNA-Seq , Dedos de Zinco
15.
Reprod Toxicol ; 107: 97-103, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896591

RESUMO

The ovary is a highly organized composite of germ cells and various types of somatic cells, whose communications dictate ovary development to generate functional oocytes. The differences between individual cells might have profound effects on ovary functions. Single cell RNA sequencing techniques are promising approaches to explore the cell type composition of organisms, the dynamics of transcriptomes, the regulatory network between genes and the signaling pathways between cell types at the single cell resolution. In this review, we provide an overview of the currently available single cell RNA sequencing techniques including Smart-seq2 and Drop-seq, as well as their applications in biological and clinical research to provide a better understanding on the molecular mechanisms underlying ovary development and associated diseases.


Assuntos
Doenças Ovarianas/genética , Ovário/crescimento & desenvolvimento , Análise de Sequência de RNA , Animais , Feminino , Perfilação da Expressão Gênica , Humanos , Análise de Célula Única , Transcriptoma
16.
J Dev Orig Health Dis ; 13(1): 49-60, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650479

RESUMO

17α-Ethinylestradiol is an endocrine-disrupting chemical that make up most contraceptive pills and can be found in the environment. Exposure to ethinylestradiol in different development periods may promote changes in morphophysiological parameters of reproductive and endocrine organs. Considering that the effects of low doses (15 µg/kg/day) of ethinylestradiol in ovaries from 12-month-old female gerbils (Meriones unguiculatus) were investigated. Four experimental groups used were control (without treatment), EE/PRE (treated from the 18th to the 22nd gestational day), EE/PUB (treated from the 42nd to the 49th day of life), and EE/PRE-PUB (treated in the both periods). The animals were euthanized at 12 months. Testosterone and 17ß-estradiol levels were measured. The ovaries were stained with Hematoxylin and Eosin, Periodic Acid Schiff, and Gomori's Trichome. The follicles, corpus luteum, interstitial gland, lipofuscin, ovarian epithelium, and tunica albuginea were analyzed. Estradiol was higher in EE/PRE and EE/PUB groups, while testosterone was higher only in EE/PUB group. The main changes in follicle count occurred in EE/PUB and EE/PRE-PUB groups, with higher primordial follicle count and lower maturation of follicles. The corpus luteum was more evident in EE/PRE group. No differences were found in atretic follicles count. A higher area occupied by interstitial gland cells and lipofuscin deposit in these cells was noted in EE/PUB and EE/PRE-PUB groups. Higher epithelium height and thicker tunic albuginea were showed in treated groups. These results suggest that exposure to doses of EE2 in prenatal and pubertal periods of the development leads to morphological changes in senile ovaries.


Assuntos
Etinilestradiol/análogos & derivados , Folículo Ovariano/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Animais , Modelos Animais de Doenças , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Etinilestradiol/efeitos adversos , Feminino , Gerbillinae/genética , Gerbillinae/crescimento & desenvolvimento , Gerbillinae/metabolismo , Folículo Ovariano/fisiopatologia , Ovário/fisiopatologia
17.
BMC Vet Res ; 17(1): 344, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732186

RESUMO

BACKGROUND: The ewe lamb nutritional and physiological state interfere with the ovarian environment and fertility. The lack or excess of circulating nutrients reaching the ovary can change its gene expression. A protein deficiency in the blood caused by an Haemonchus contortus abomasal infection is detrimental to the organism's development during puberty. The peripubertal period is a time of intensive growth that requires a high level of nutrients. An essential feature controlling pubertal arousal and female reproductive potential is ovarian follicle growth activation. Protein supplementation improves the sheep's immune response to helminthic infections. We aimed to determine if supplementing protein in infected ewe lambs' diet would impact the ovarian environment leading to earlier ovarian follicle activation than in infected not supplemented animals. METHODS: We fed 18 Santa Ines ewe lambs (Ovis aries) - bred by the same ram - with either 12% protein (Control groups) or 19% protein (Supplemented groups) in their diets. After 35 days of the diet, they were each artificially infected or not with 10,000 Haemonchus contortus L3 larvae. Following 77 days of the diet and 42 days of infection, we surgically collected their left ovaries and examined their genes expression through RNA sequencing. RESULTS: We found that protein supplementation in infected animals led to an up-regulation of genes (FDR p-values < 0.05) and biological processes (p-value cut-off = 0.01) linked to meiotic activation in pre-ovulatory follicles and primordial follicle activation, among others. The supplemented not infected animals also up-regulated genes and processes linked to meiosis and others, such as circadian behaviour. The not supplemented animals had these same processes down-regulated while up-regulated processes related to tissue morphogenesis, inflammation and immune response. CONCLUSION: Diet's protein supplementation of peripubertal infected animals allowed them to express genes related to a more mature ovarian follicle stage than their half-sisters that were not supplemented. These results could be modelling potential effects of the interaction between environmental factors, nutrition and infection on reproductive health. When ovarian activation is achieved in a timely fashion, the ewe may generate more lambs during its reproductive life, increasing sheep breeders' productivity.


Assuntos
Dieta/veterinária , Hemoncose/veterinária , Ovário/crescimento & desenvolvimento , Doenças dos Ovinos/parasitologia , Animais , Proteínas na Dieta , Feminino , Expressão Gênica , Haemonchus , Ovário/metabolismo , Ovinos , Carneiro Doméstico
18.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34635592

RESUMO

Male mating harassment may occur when females and males do not have the same mating objectives. Communal animals need to manage the costs of male mating harassment. Here, we demonstrate how desert locusts in dense populations reduce such conflicts through behaviors. In transient populations (of solitarious morphology but gregarious behavior), we found that nongravid females occupied separate sites far from males and were not mating, whereas males aggregated on open ground (leks), waiting for gravid females to enter the lekking sites. Once a male mounted a gravid female, no other males attacked the pair; mating pairs were thereby protected during the vulnerable time of oviposition. In comparison, solitarious locusts displayed a balanced sex ratio in low-density populations, and females mated irrespective of their ovarian state. Our results indicate that the mating behaviors of desert locusts are density dependent and that sex-biased behavioral group separation may minimize the costs of male mating harassment and competition.


Assuntos
Gafanhotos/fisiologia , Comportamento Sexual Animal , Animais , Feminino , Masculino , Ovário/crescimento & desenvolvimento , Razão de Masculinidade
19.
Biochem Biophys Res Commun ; 582: 21-27, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34678592

RESUMO

The chicken has a Z-W sex chromosome system, in which the males are the homogametic sex (ZZ) and the females the heterogametic sex (ZW). The smaller W chromosome is generally considered to be a highly degraded copy of the Z chromosome that retains around 28-30 homologous protein-coding genes' These Z-W homologues are thought to have important, but undefined, roles in development, and here we explore the role of one of these genes, VCP (Valosin Containing Protein) in gonadogenesis. We established RNA expression levels of both Z and W VCP homologues, the levels of VCP protein, and the cellular localization of VCP protein in male and female embryonic gonads during development. We also assessed the effects of female-to-male sex-reversal on VCP expression in developing gonads. The results showed that both VCP RNA and protein are expressed at higher levels in female than male gonads, and the expression levels of VCP protein and VCP-Z transcript, but not VCP-W transcript, are decreased in female-to-male sex reversed gonads. In addition, the spatial expression of VCP protein differs between male and female embryonic gonads: in testes, VCP protein is mainly confined to the medullary sex cords, while in ovaries, VCP protein is expressed throughout the medulla and at higher levels in the cortex. The results suggest that sexually dimorphic expression of chicken VCP reflects differences in gonadal morphology between sexes.


Assuntos
Galinhas/genética , Ovário/metabolismo , Caracteres Sexuais , Cromossomos Sexuais/química , Testículo/metabolismo , Proteína com Valosina/genética , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Embrião não Mamífero , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Ovário/crescimento & desenvolvimento , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Testículo/crescimento & desenvolvimento , Proteína com Valosina/metabolismo
20.
Elife ; 102021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590579

RESUMO

Production of proliferative follicle cells (FCs) and quiescent escort cells (ECs) by follicle stem cells (FSCs) in adult Drosophila ovaries is regulated by niche signals from anterior (cap cells, ECs) and posterior (polar FCs) sources. Here we show that ECs, FSCs, and FCs develop from common pupal precursors, with different fates acquired by progressive separation of cells along the AP axis and a graded decline in anterior cell proliferation. ECs, FSCs, and most FCs derive from intermingled cell (IC) precursors interspersed with germline cells. Precursors also accumulate posterior to ICs before engulfing a naked germline cyst projected out of the germarium to form the first egg chamber and posterior polar FC signaling center. Thus, stem and niche cells develop in appropriate numbers and spatial organization through regulated proliferative expansion together with progressive establishment of spatial signaling cues that guide adult cell behavior, rather than through rigid early specification events.


Assuntos
Drosophila melanogaster/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Células-Tronco/metabolismo , Animais , Feminino , Pupa/crescimento & desenvolvimento
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