127 Chemokine receptor 2 (CCR2) is expressed in growing oocytes, and its deficiency affects follicular activation and long-term female fertility in mice

2020 ◽  
Vol 32 (2) ◽  
pp. 190
Author(s):  
A. G. A. Santos ◽  
L. A. A. C. Pereira ◽  
R. C. Russo ◽  
J. H. M. Viana ◽  
P. H. A. Campos-Junior
Keyword(s):  
Chemokine Receptor ◽  
Adult Life ◽  
Rna Isolation ◽  
Antral Follicle ◽  
Immunoperoxidase Staining ◽  
P Value ◽  
Primordial Follicles ◽  
Ovarian Weight ◽  
Rabbit Igg ◽  
Follicular Reserve

Chemokine receptor 2 (CCR2) has important functions in several biological processes, including activation of PI3K/Akt/mTOR signalling, a key pathway in follicular activation. However, there is no report about the role of CCR2 in ovarian follicular physiology. The objectives of this study were (1) to immunolocalize CCR2 in mice ovaries and (2) to evaluate the effects of CCR2 deficiency on follicular growth during adult life and aging. A total of 74 C57Bl/6 (wild type, WT) and 68 B6.129S4-Ccr2tm1Ifc/J (CCR2−/− (knockout)) female mice were used. For objective 1, ovaries were collected from WT mice at 1.5 months old (m.o.), fixed in 4% PFA, embedded in paraffin, and used for immunoperoxidase staining with an anti-CCR2 antibody [EPR19698] (ab222496; 1:200) and using anti-rabbit IgG (Ab6721, 1:100) as a secondary antibody. Also, MII oocytes from oviducts of superovulated WT mice were processed with the same primary antibody for immunofluorescence. For objective 2, body and ovarian weight were evaluated. Follicle populations were assessed in WT and CCR2−/− mice at 1.5, 2.5, 6, 10, and 12m.o., by serial sectioning; the total follicle population was counted in every third section in the whole ovary. Additionally, ovarian total RNA isolation was performed from WT and CCR2−/−. Real-time PCR was used to evaluate differential gene expression according to standard protocols, using primers for Bax, Casp3, Bcl2, Fshr, and B-actin (endogenous control). The data were analysed using the GraphPad Prism Software, using t-test, and a P-value of 0.05 was considered as significant. Localization of CCR2 was observed exclusively on the membrane and cytoplasm of growing oocytes in primary, secondary, antral, and atretic follicles, as well as on ovulated MII oocytes membrane and cytoplasm. Body and ovarian weight were similar between WT and CCR2−/− mice. At 1.5m.o., CCR2−/− mice had more primordial follicles and fewer primary and secondary follicles compared with WT (P<0.05), whereas there was no difference in the antral follicle populations. Follicular activation (primordial to primary transition) and atresia rates were decreased in CCR2−/− (P<0.05) at 1.5m.o. A downregulation of pro-apoptotic genes (Bax and Casp3) was observed on CCR2−/− (P<0.05), while anti-apoptotic Bcl2 was upregulated (P<0.05) compared with WT in 1.5-m.o. animals. A larger ovarian follicular reserve at 1.5, 2.5, and 6m.o., but not at 10 or 12m.o., was observed in CCR2−/− mice. At 6 to 12m.o., CCR2−/− ovulated more (P<0.05) MII oocytes than WT. Altogether, these data may suggest that CCR2 plays an important role in the regulation of ovarian follicular reserve mobilization, potentially affecting reproductive lifespan. Financial support was provided by Fapemig and CNPq.

P–449 Evaluation of ovarian reserve in female children and adolescents with non-iatrogenic primary ovarian insufficiency to establish criteria for ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Predictive Value ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Antral Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Positive Parameter ◽  
Primordial Follicles

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH > 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

138 Relationships Between Antral Follicle Count, Ovarian Volume, Pre-Antral Follicle Number, and Oocyte Quality

2018 ◽  
Vol 30 (1) ◽  
pp. 209
Author(s):  
G. L. Vasconcelos ◽  
R. Maculan ◽  
N. Alves ◽  
A. L. A. P. L. Ribeiro ◽  
A. W. B. Silva ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Antral Follicle ◽  
Oocyte Quality ◽  
Antral Follicle Count ◽  
Primary Follicle ◽  
Ovarian Volume ◽  
Primordial Follicles ◽  
Antral Follicles ◽  
Grade 3

The objective was to evaluate the possible relationships between AFC, ovarian volume, ovarian follicle reserve and oocyte quality in abattoir-derived ovaries (experiment 1) and in cows (experiment 2) submitted to OPU. Antral follicle counts of ≥25, 16 to 24, and ≤ 16 were used to define AFC classes as high (HAFC), intermediate (IAFC), and low (LAFC) in both experiments. In experiment 1, after antral follicles were aspirated, abattoir ovaries (n = 10 per AFC class) were processed by conventional histology and pre-antral follicles were counted within primordial, primary, secondary, and tertiary classes and classified as either healthy or degenerate under regular microscopy (Cushman et al. 1999). In experiment 2, HAFC (n = 42), IAFC (n = 34), and LAFC (n = 29) cows were submitted to OPU and oocytes classified as grades 1, 2, and 3 or degenerate (IETS, 2010). Antral follicles (≥3 mm in diameter) were counted by ultrasonography. Data were analysed by GENMOD and GLM procedures of SAS (SAS Institute Inc., Cary, NC, USA) after transformations, when required. In experiment 1, mean normal primordial follicle number was higher (P < 0.001) in HAFC (137.0 ± 1.6)a compared with IAFC (52.6 ± 1.9)b and LAFC (20.2 ± 5.3)c ovaries. However, the mean number of degenerate primordial follicles was lower (P < 0.001) in low count ovaries (2.4 ± 0.6) compared with HAFC (19.0 ± 4.7) and IAFC (16.4 ± 1.5, P < 0.001). Normal primary follicle number was higher in the HAFC compared with IAFC and LAFC ovarian classes (86.2 ± 7.0a v. 34.6 ± 5.1b and 14.4 ± 3.3c, respectively; P < 0.01). Degenerate primary follicles were higher in the HAFC compared with LAFC ovarian class (16.8 ± 6.5 v. 5.2 ± 2.64; P < 0.05). Normal secondary follicle number was also higher in the HAFC compared to LAFC ovarian classes (25.2 ± 7.67 v. 2.4 ± 0.8; P < 0.05). The number of degenerate secondary follicles differed (P < 0.01) only between the IAFC and the LAFC ovarian classes (0.6 ± 0.4 and 7.2 ± 2.4, respectively), which were similar (P > 0.5) to the HAFC class (3.8 ± 1.0). In experiment 2, grade 1, 2, and 3 oocytes, viable oocytes, and ovarian volume (mm3) were higher (P < 0.001) in HAFC compared with IAFC and LAFC cows (grade 1: 7.9 ± 0.6a, 4.9 ± 0.7b and 3.3 ± 0.7c; grade 2: 4.0 ± 0.4a, 2.8 ± 0.4b and 1.2c; grade 3: 2.1 ± 0.4a, 2.5 ± 0.4a and 1.3 ± 0.5b, respectively; viable oocytes: 16.3 ± 1.1a, 13.1 ± 1.2b, and 8.1 ± 1.3c, respectively; (volumes: 12.6 ± 0.7a, 10.1 ± 0.8b, and 8.1 ± 0.9c, respectively). In conclusion, high AFC is linked to a higher follicular reserve, oocyte quality, and ovarian volume. It is safe to apply AFC in the selection of bovine females without compromising oocyte or pre-antral follicular population qualities.

scholarly journals Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice

Reproduction ◽  
2006 ◽  
Vol 131 (3) ◽  
pp. 525-532 ◽  
Author(s):  
Karin A Slot ◽  
Jan Kastelijn ◽  
Anne Bachelot ◽  
Paul A Kelly ◽  
Nadine Binart ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Laron Syndrome ◽  
Knock Out ◽  
Primordial Follicles ◽  
Antral Follicles ◽  
Gh Receptor ◽  
Igf I ◽  
Follicular Reserve ◽  
Deficient Mice ◽  
Insight Into

GH influences female fertility. The goal of the present study was to obtain more insight into the effect of loss of GH signalling, as observed in humans suffering from Laron syndrome, on ovarian function. Therefore, serial paraffin sections of ovaries of untreated and IGF-I-treated female GH receptor knock-out (GHR/GHBP-KO) mice were examined to determine the follicular reserve and the percentage of follicular atresia in each ovary. Our observations demonstrate that the amount of primordial follicles was significantly elevated in GHR/GHBP-KO mice, while the numbers of primary, preantral and antral follicles were lower compared with wild-type values. The reduced number of healthy growing follicles in GHR/GHBP-KO mice was accompanied by a significant increase in the percentage of atretic follicles. IGF-I treatment of GHR/GHBP-KO mice for 14 days resulted in a reduced number of primordial follicles, an increased number of healthy antral follicles, and a decreased percentage of atretic follicles. The results of the present study suggest that GH may play a role, either directly or indirectly, via for instance IGF-I, in the recruitment of primordial follicles into the growing pool. Furthermore, GH seems to protect antral follicles, directly or indirectly from undergoing atresia.

scholarly journals IMPACT OF EDUCATIONAL INTERVENTION ON SMOKING KNOWLEDGE, ATTITUDE AND BEHAVIOR OF ADOLESCENTS IN SCHOOLS OF DEVELOPING COUNTRY [RAWALPINDI PAKISTAN].

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Prof Dr Ishaq Khan ◽  
Junaid Ishaq Khan ◽  
Rohail Khan
Keyword(s):  
Health Education ◽  
Educational Intervention ◽  
Smoking Habit ◽  
Adult Life ◽  
Early Years ◽  
P Value ◽  
Education Intervention ◽  
Quit Smoking ◽  
And Behavior ◽  
The Impact

Background: Smoking is one of the leading preventable causes of mortality and morbidity, Adolescent are more prone to develop smoking habit and continues it into adult life. Early smokers are associated with increased number of cigarettes uptake in adulthood and decreased quit rates. It is stated that adult smokers usually initiate smoking in their early years and there are less chances that they cease smoking in their adulthood. Objectives: The study aims to evaluate the impact of educational intervention on knowledge, attitude and behavior of adolescent aged 14-19 years. Materials and Methods: A cross sectional study followed by an education intervention was conducted from June 2017 to August 2018.  650 adolescents who were found to be current smokers were included in this study. Data was analyzed using SPSS. Chi square test was applied at p value of 0.05. Results: Before intervention 90.7% adolescent considered smoking as a bad habit which significantly increases to 96.9% after educational intervention. Significant improvement in attitude of respondents was seen after intervention. Proportion of adolescent who intend to quit smoking increases from 35.2% to 72.2% after educational intervention. As a result of an educational intervention proportion of adolescent who uses complete stick at one time decreases from 83.5% to 65%. Conclusion: Health education on smoking is effective in motivating adolescents to quit smoking. In order to reduce smoking rates among adolescent’s education intervention strategies should be adopted at large scale. It is recommended that health education program on smoking should be organized by schools and colleges which will lead to overall low smoking prevalence. Keywords: Adolescents, Smoking, Knowledge, Health education

scholarly journals Survival factors regulating ovarian apoptosis -- dependence on follicle differentiation

Reproduction ◽  
2002 ◽  
pp. 23-30 ◽  
Author(s):  
E Markstrom ◽  
ECh Svensson ◽  
R Shao ◽  
B Svanberg ◽  
H Billig
Keyword(s):  
Growth Factor ◽  
Follicular Development ◽  
Antral Follicle ◽  
Short Review ◽  
Ovarian Follicles ◽  
Survival Factors ◽  
Primordial Follicles ◽  
Survival Factor ◽  
Fetal Ovary

Only a minute fraction of the ovarian follicles present in a fetal ovary will complete the path to ovulation. Most of the follicles will undergo atresia, a hormonally controlled apoptotic process. Apoptosis occurs at each stage of follicular development and there is a marked reduction in the number of follicles present at birth. Stage-dependent mechanisms of follicle survival can be postulated to achieve co-ordinated development, leading to ovulation of a small fraction of follicles. Indeed, hormone and growth factor regulation of follicular atresia is stage-specific. This short review considers the factors that promote survival of ovarian follicles throughout development, including endocrine, locally produced and intracellular mediators, as exemplified mainly by follicular development in rodents. In primordial follicles, oocyte apoptosis is considered to be the cause of subsequent follicle degeneration. In slow-growing preantral follicles, FSH is not a survival factor, but some locally produced growth factors are. Progression to the antral follicle stage is probably the most critical stage of follicle development in vivo, and FSH is a major survival factor at this stage. In addition, insulin-like growth factor I and interleukin 1beta are potent survival factors for cultured rat follicles at the antral stage. Preovulatory follicles express receptors for LH, and both of the gonadotrophins are survival factors at this stage. Relatively little is known about the period between the LH surge and ovulation; however, it has been suggested that at this stage progesterone acts as a survival factor.

Carma1 Is Important for T-ALL CNS Infiltration and Survival in an Animal Model of T-ALL

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 934-934
Author(s):  
Sreenivasa Rao Oruganti ◽  
Christina Halsey ◽  
Savannah Krebsbach ◽  
Francois Asperti-Boursin ◽  
Sumit Patel ◽  
...  
Keyword(s):  
Animal Model ◽  
T Cells ◽  
Cell Migration ◽  
Chemokine Receptor ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Xenograft Model ◽  
Leukemic Cell ◽  
Tumor Burden ◽  
P Value

Abstract Acute lymphoblastic leukemia (ALL) is one of the most common childhood cancer, and can arise from the T or B cell lineage (T-ALL or B-ALL respectively). T-ALL patients have almost 80% cure rate, however leukemic cell migration to the central nervous system (CNS) remains a major therapeutic challenge. Little is known about potential regulators of T-ALL cell migration to the CNS, and identifying new molecules that can drive T-ALL to the CNS may provide new targets for drug therapy to specifically block T-ALL CNS infiltration. Recently it has been shown that a chemokine receptor CCR7 is an essential regulator of T-ALL cell infiltration into the CNS. CCR7 is a homeostatic chemokine receptor expressed on T cells that controls the homing of cells to lymph nodes, including na•ve T cells, dendritic cells, and lymphoma cells. Aberrant CCR7 expression has also been associated with migration of gastric, breast and head and neck cancers. We recently identified the molecule CARMA1 as a signaling mediator that acts downstream of CCR7. We now find that CARMA1 regulates CNS migration in T-ALL. We have established a xenograft model of T-ALL, where we can assess the engraftment of a T-ALL cell line into the NOD/SCID/IL2Rγ2 immunodeficient mice. Using luciferase expressing T-ALL cells lacking CARMA1, we imaged tumor load using the IVIS imaging system. Animals receiving T-ALL cells lacking CARMA1 show a significant delay in the timing of leukemia development as well as longer overall survival compared to animals receiving wild type T-ALL cells (n=25, P value < 0.0001). In addition, animals injected with CARMA1-knockdown T-ALL cells have lower tumor burden in the brain. In some cases, no tumor cells were found in the brains of animals receiving CARMA1-knockdown T-ALL cells. Using immunohistochemistry and flow cytometry, we also find lower tumor burden in liver and spleen of mice injected with CARMA1-knockdown T-ALL cells compared to WT cells. We confirmed the role of CARMA1 in a NOTCH1ΔE-induced T-ALL animal model. Similar to the xenograft model, we find that mice receiving CARMA1KO-Notch1ΔE survived longer than mice receiving with WT- Notch1ΔE. These results demonstrate for the first time that CARMA1 may play an important role in T-ALL induction and leukemic cell migration to the CNS. Numerous studies have demonstrated the importance of CARMA1 in normal T cell function. We now find that CARMA1 is also involved in controlling the migration of T-ALL cells to the CNS as well as survival of animals with T-ALL. These results suggest that CARMA1 may provide a novel therapeutic target in T-ALL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals EFFECT OF CALORIC RESTRICTION AND RAPAMYCIN ON OVARIAN AGING IN MICE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S103-S103
Author(s):  
Driele Garcia ◽  
Tatiana Saccon ◽  
Joao Rincon ◽  
Jorgea Pradiee ◽  
Rafael Mondadori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Caloric Restriction ◽  
Primordial Follicle ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Primordial Follicles ◽  
Female Mice ◽  
Insulin Tolerance ◽  
Follicular Reserve

Abstract The ovarian follicular reserve of primordial follicle declines with aging in female mammals. Caloric restriction (CR) has been shown to increase the preservation of the ovarian follicular reserve. Likewise, rapamycin has similar effects to CR on the ovarian reserve. Therefore, the aim of our study was to evaluate the effects of rapamycin and CR on the metabolism and ovarian follicular reserve and gene expression in mice. Thirty-six female mice were used, and allocated into 3 groups: control, rapamycin (4mg/kg body weight every other day) and 30% CR. At 85 days of treatment, an insulin tolerance test (ITT) and glucose tolerance test (GTT) was performed. At 93 days ovaries were collected for analysis. CR females had lower body weight (P&lt;0.05) and were more insulin sensitive (P=0.003), while rapamycin treated females did not change body weight (P&gt;0.05) and were more resistant to insulin (P&lt;0.05). Females from the CR and rapamycin groups had a twice higher number of primordial follicles (P=0.02 and 0.04) and half the number of primary, secondary and tertiary follicles (P&lt;0.05). Both CR and rapamycin females had increased ovarian gene expression of Foxo3a mRNA (P&lt;0.05). In conclusion, female mice from rapamycin and CR groups had an increased ovarian follicular reserve associated to higher expression of Foxo3a mRNA, despite divergent metabolic effects of the treatments.

Effects of plant polyphenols on ovarian follicular reserve in aging ratsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 737-745 ◽  
Author(s):  
Zhen-Guo Chen ◽  
Li-Li Luo ◽  
Jin-Jie Xu ◽  
Xiao-Lan Zhuang ◽  
Xiao-Xia Kong ◽  
...  
Keyword(s):  
Peer Review Process ◽  
Tea Polyphenols ◽  
Intragastric Administration ◽  
Tea Polyphenol ◽  
Plant Polyphenols ◽  
Primary Follicle ◽  
Primordial Follicles ◽  
Positive Effects ◽  
Follicular Reserve ◽  
Selection Of

The pool of ovarian primordial follicles is established during embryonic development or at birth. During the development from primordial to primary, secondary, and antral follicles, only a small portion of follicles can mature and successfully ovulate; the others are destined to degenerate through apoptotic or atretic loss. As aging advances, females ultimately enter the cessation phase of the estrous cycle and are no longer capable of fertilization. The presumption is that if we can slow down the process of folliculogenesis or decrease follicle loss, females may have a larger ovarian follicular reserve and a longer reproductive lifespan. In our study, rats underwent intragastric administration with tea polyphenols, quercetin (meletin), genistein, or resveratrol, once a day for 4 months (from age 12 to 15 months), to test whether they have positive effects on follicular reserve or ovarian functions. The results showed that rats treated with tea polyphenols (27.8 ± 3.2) and quercetin (36.5 ± 4.1) had a comparable number of healthy follicles to those of controls (26.9 ± 3.8), although significantly fewer atretic follicles were observed in the tea polyphenol group (43.4 ± 5.9 vs 79.7 ± 7.5; p < 0.001). Remarkably, both genistein- and resveratrol-treated rats had more healthy follicles (respectively, 42.8 ± 3.9, p < 0.05; and 51.9 ± 6.4, p < 0.001) and fewer atretic follicles (respectively, 58.4 ± 8.0, p < 0.05; and 51.0 ± 6.2, p < 0.01) than controls. These results indicate that genistein and resveratrol can increase the ovarian follicular reserve and prolong the ovarian lifespan in rats, and their positive effects may be not only due to their intervention in the transition from primordial to primary follicle, but also due to the inhibiting effect on follicular atresia.

scholarly journals Mammalian foetal ovarian development: consequences for health and disease

Reproduction ◽  
2012 ◽  
Vol 143 (2) ◽  
pp. 151-163 ◽  
Author(s):  
Mai A Sarraj ◽  
Ann E Drummond
Keyword(s):  
Molecular Mechanisms ◽  
Ovarian Development ◽  
Primordial Germ Cells ◽  
Adult Life ◽  
Primordial Follicles ◽  
Cellular Processes ◽  
Foetal Life ◽  
Health And Disease ◽  
Female Specific ◽  
Bipotential Gonad

The development of a normal ovary during foetal life is essential for the production and ovulation of a high-quality oocyte in adult life. Early in embryogenesis, the primordial germ cells (PGCs) migrate to and colonise the genital ridges. Once the PGCs reach the bipotential gonad, the absence of the sex-determining region on the Y chromosome (SRY) gene and the presence of female-specific genes ensure that the indifferent gonad takes the female pathway and an ovary forms. PGCs enter into meiosis, transform into oogonia and ultimately give rise to oocytes that are later surrounded by granulosa cells to form primordial follicles. Various genes and signals are implicated in germ and somatic cell development, leading to successful follicle formation and normal ovarian development. This review focuses on the differentiation events, cellular processes and molecular mechanisms essential for foetal ovarian development in the mice and humans. A better understanding of these early cellular and morphological events will facilitate further study into the regulation of oocyte development, manifestation of ovarian disease and basis of female infertility.

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