196 GLUTATHIONE S-TRANSFERASE THETA1 (GSTT1) IS DIFFERENTIALLY REGULATED FROM OTHER GLUTATHIONE S-TRANSFERASES IN GRANULOSA CELLS

2011 ◽  
Vol 23 (1) ◽  
pp. 198
Author(s):  
M. Muraki ◽  
Y. Takahashi ◽  
T. Ishii ◽  
S. Kyuwa ◽  
Y. Yoshikawa
Keyword(s):  
Granulosa Cells ◽  
Expression Patterns ◽  
Oocyte Quality ◽  
Water Soluble ◽  
Regulation Mechanism ◽  
Related Factor ◽  
Age Related ◽  
Significant Difference ◽  
Glutathione S Transferases ◽  
The Difference

Oxidative stress is a major source of aging that damages genomic and mitochondrial DNA, causing female reproductive disorders. Glutathione S-transferases (GST) are known to detoxify the metabolites of genotoxic molecules to more water-soluble and readily excretable forms. Therefore, most GST have been considered to be down-regulated by aging. We recently demonstrated that only GSTT1 is up-regulated in granulosa cells from aged, infertile patients and aged mice, although other kinds of GST are down-regulated in these cells (Ito et al. 2008 Fertil. Steril. 90, 1026–1035). Measurement of the GSTT1 level in granulosa cells binding to the patient’s oocytes could be used in the selection of oocytes of high quality, meaning that the GSTT1 level in granulosa cells could be a good indicator of age-related infertility. To do that, an understanding of the concrete relationship between aging and GSTT1 up-regulation is necessary. However, the regulation mechanism of GSTT1 in granulosa cells remains unclear. In the present study, we attempted to examine the difference in expression mechanisms between GSTT1 and other GST. First, the expression patterns of GSTT1 and GSTP (a major member of the GST) in aged granulosa cells from patients were observed by immunostaining. The GSTT1 was up-regulated (young: 25 to 34 years old, N = 9; aged: 38 to 43 years old, N = 12; P < 0.05) but the GSTP was down-regulated (young: 28 to 30 years, N = 5; aged: 38 to 42 years, N = 7; P < 0.05) in the aged group. Nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is a transcription factor that regulates the expression of most GST, so in the next experiment, we examined the expression patterns of GSTT1 and GSTP in granulosa cells from Nrf2-disrupted (Nrf2–/–) mice by immunostaining. The GSTP was down-regulated in granulosa cells of Nrf2–/– mice compared with those of Nrf2+/– mice, although a significant difference was not observed in GSTT1. In addition, we confirmed these results by using mouse embryonic fibroblasts (MEF) from Nrf2–/– and Nrf2+/– mice, and the same results were obtained. Our previous experiment showed that GSTT1 was induced by FSH in human granulosa-like tumour cells (KGN cells). We analysed the expression level of other genes in FSH-stimulated KGN cells. The transcription levels of GSTP and Nrf2 were not induced by FSH. These results suggest that the expression of GSTT1 is not regulated by Nrf2 and is differentially regulated from other GST. The difference in regulation mechanisms between GSTT1 and other GST may result in the up-regulation of GSTT1 in the aging granulosa cells, and it may contribute to the constitution of the diagnosis of oocyte quality using the GSTT1 measurement.

scholarly journals Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos

2021 ◽  
Vol 22 (10) ◽  
pp. 5327
Author(s):  
Lianguang Xu ◽  
Muhammad Idrees ◽  
Myeong-Don Joo ◽  
Tabinda Sidrat ◽  
Yiran Wei ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Constitutive Expression ◽  
Growth Factor Receptor ◽  
Oocyte Quality ◽  
Low Fertility ◽  
Treatment Groups ◽  
Age Related ◽  
Early Embryos ◽  
Plasmid Injection ◽  
Telomere Lengthening

Age-associated decline in oocyte quality is one of the dominant factors of low fertility. Aging alters several key processes, such as telomere lengthening, cell senescence, and cellular longevity of granulosa cells surrounding oocyte. To investigate the age-dependent molecular changes, we examined the expression, localization, and correlation of telomerase reverse transcriptase (TERT) and β-Klotho (KLB) in bovine granulosa cells, oocytes, and early embryos during the aging process. Herein, cumulus-oocyte complexes (COCs) obtained from aged cows (>120 months) via ovum pick-up (OPU) showed reduced expression of β-Klotho and its co-receptor fibroblast growth factor receptor 1 (FGFR1). TERT plasmid injection into pronuclear zygotes not only markedly enhanced day-8 blastocysts’ development competence (39.1 ± 0.8%) compared to the control (31.1 ± 0.5%) and D-galactose (17.9 ± 1.0%) treatment groups but also enhanced KLB and FGFR1 expression. In addition, plasmid-injected zygotes displayed a considerable enhancement in blastocyst quality and implantation potential. Cycloastragenol (CAG), an extract of saponins, stimulates telomerase enzymes and enhances KLB expression and alleviates age-related deterioration in cultured primary bovine granulosa cells. In conclusion, telomerase activation or constitutive expression will increase KLB expression and activate the FGFR1/β-Klotho pathway in bovine granulosa cells and early embryos, inhibiting age-related malfunctioning.

scholarly journals Investigation of Fasting Plasma Glucose in Masters Athletes

2020 ◽  
Vol 4 (2) ◽  
pp. 65-68
Author(s):  
Joe Walsh ◽  
◽  
Ian Timothy Heazlewood ◽  
Mark DeBeliso ◽  
Mike Climstein ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Sport Participation ◽  
Past Research ◽  
Fasting Plasma ◽  
Age Related ◽  
Significant Difference ◽  
Masters Athletes ◽  
The Mean ◽  
The Difference

Prior research documented differences in fasting plasma glucose (FPG) between older and younger masters athletes at the Golden Oldies Rugby Festival (GORF). It was the purpose of our study to further investigate FPG on a larger sample. FPG data was collected on 486 participants at the Sydney World Masters Games. Of the males, 241 reported optimal FPG and 36 reported sub-optimal FPG. For females 183 reported optimal FPG and 26 reported sub-optimal FPG. Analysis was conducted utilising the age ranges implemented in past research on the GORF. The mean FPG for masters athletes below 50 years old was 5.10±1.52 mmol/L, whilst for those 50 years and above it was 5.01±1.02. The difference between the groups was not significant (t = 0.722, p = 0.471). This aligned with the finding of the GORF study that there was no significant difference in FPG between the different age ranges analysed. The sample size obtained for this investigation of FPG in masters athletes was more than double the number of participants used in previous research on the GORF. Many participants had FPG above optimal levels. Therefore, an age-related decline in pancreatic function may outweigh protective exercise benefits attained from masters sport participation.

Is Age Related Fibrinogen Affected by Warfarin?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4117-4117
Author(s):  
Roger C. Munro ◽  
Lisa J. Wakeman ◽  
Saad Al-Ismail
Keyword(s):  
Statistical Significance ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Warfarin Group ◽  
Published Evidence ◽  
Age Related ◽  
Age Gap ◽  
Significant Difference ◽  
Warfarin Treatment ◽  
The Difference

Abstract Introduction: There is published evidence which indicates that advancing age may be associated with higher plasma concentrations of fibrinogen. There is also evidence that derived fibrinogen values are significantly higher than Clauss measurements and that this discrepancy is greater in patients receiving warfarin. The purpose of this study was to determine whether age related derived fibrinogen levels are similar in both warfarin and non-warfarin groups. Methods: Venous samples were collected into siliconised glass B-D Vacutainers containing tri-sodium citrate (Ref: 367691) from 1000 patients receiving long term warfarin treatment and an equal number of age-matched patients not receiving warfarin. Genders were equally represented in both groups. Patients in both groups were categorized into 5 years age bands as follows: &lt;40 n=23: 40–44 n=20: 45–49 n=43; 50–54 n=74: 55–59 n=113: 60–64 n=155: 65–69 n=178: 70–74 n=191: 75–79 n=124; 80–84 n=56: 85–89 n=23. Derived fibrinogen was measured in each patient on an ACL300R coagulometer (I L) within 1 hour of collection using IL PT-FIB HS Plus reagent and following the manufacturer’s protocol. Appropriate CLSI guidelines were followed throughout. A normal probability plot of the data was performed to confirm that it did not deviate too much from the normal distribution. Results: The T-test for independent samples using the separate variance estimate showed that there was a statistically significant difference in the mean fibrinogen between patients on warfarin and those not on warfarin (p&lt;0.05) in each group except for the last (85–89 years). There was a statistically significant difference (ANOVA) in the fibrinogen levels of patients of different age in both warfarinised and non-warfarinised groups (p&lt;0.05). The modified least significance procedure in the ANOVA test showed that in the non-warfarin group, most of significant difference in fibrinogen between the different age groups is contributed by the difference between patients under 50 years of age. In the non-warfarin group, it requires an age gap of at least 20 years for the difference in fibrinogen to be statistically significant but in the warfarin group, it only requires an age gap of ten years (p&lt;0.05). Both Linear Regression and Cross Tabulation indicate that the relationship between fibrinogen and age does not vary whether or not the patient is on warfarin. These also show that the effect of age on fibrinogen is not affected by warfarin treatment. Conclusion: Differences or correlations detected in this analysis are of statistical significance but not necessarily clinically significant. Placing age and warfarin treatment in the same model shows that variations in fibrinogen have to be explained by other factors (e.g. technical) not included in the study as only 12% of the error in predicting fibrinogen levels can be reduced by knowing both the age and status of warfarin treatment in individual patients.

HOX Genes Expression Pattern Is Related to Phenotypical and Genotypical Subgroups but Not to Treatment Response in Pediatric ALL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1288-1288
Author(s):  
Julia Starkova ◽  
Blanka Vicenova ◽  
Roman Krejci ◽  
Harry A. Drabkin ◽  
Jan Trka
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Hox Genes ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Expression Patterns ◽  
Hox Gene ◽  
Age Related ◽  
Genes Expression ◽  
Significant Difference

Abstract Abstract 1288 Poster Board I-310 Homeodomain (HOX) genes encode transcription factors important for embryonic development. They are involved in normal hemopoiesis regulation and likely also in leukemogenesis as a result of translocations and other aberrations present in leukemias. In previous work Drabkin et al. demonstrated that HOX gene expression patterns differentiate major cytogenetic groups in acute myeloid leukemias. In this study we focused on HOX gene expression in pediatric acute lymphoblastic leukemias (ALL). We were interested if certain HOX genes or expression pattern could distinguish subpopulations of ALL. We analyzed the expression pattern of 21 HOX genes from HOXA and HOXB clusters and non-cluster HOX genes, CDX1 and CDX2 using qRT-PCR approach. We looked at 54 patients chosen according to phenotypic (T-ALL, BCP-ALL), prognostic (PGR – prednisone good responders, PPR – prednisone poor responders) and genotypic (BCR/ABL, MLL/AF4, TEL/AML1, hyperdiploid) characteristics. Overall analysis comparing all studied groups showed that HOXA7 (Kruskal-Wallis test p=0.000045), HOXA3 (p=0.000098), HOXB3 (p=0.00015), HOXA4 (p=0.000619) and HOXB4 (p=0.001925) genes were differently expressed among groups. Wilcoxon signed-rank test, a non-parametric statistical analysis comparing two groups against each other, showed that HOXA3, A4 and B3 distinguish BCP-ALL (w/o fusion gene) and T-ALL. Interestingly, particular HOX genes expression showed significant difference among the groups: HOXA7 gene is significantly downregulated in hyperdiploid ALL (p=0.03) compared to all other subgroups. Furthermore, HOXB7 gene is specifically upregulated in TEL/AML-positive patients (p=0.0048 vs BCP-ALL w/o fusion gene) and CDX2 is downregulated in BCR/ABL-positive patients (p=0.001 vs hyperdiploid; p=0.006 vs TEL/AML1; p=0.03 vs MLL/AF4). Suprisingly, TEL/AML1-positive patients have similar expression of HOXA1-A4 as T-ALL patients. HOX genes expression pattern seemed to differ in MLL/AF4-positive patients according to the age at diagnosis. Three patients younger than 2 months at presentation clustered together in clear contrast to the MLL/AF4-positive patient diagnosed at the age of 13 years with secALL who presented with very low overall expression of all HOX genes. Next, we looked for diversity and similarity between groups. We determined how many HOX genes were expressed differently (p<0.05) and similarly (p=1.0) between particular ALL subtypes. The most outlying couples were T-ALL vs PPR (11 genes differently expressed), T-ALL vs PGR (9 genes) and T-ALL vs TEL/AML1 (6 genes). In contrast, the closest groups were BCR/ABL vs PPR, MLL/AF4 vs T-ALL and MLL/AF4 vs PPR. Our data demonstrate that BCP-ALL (w/o known fusion gene) can be distinguished from T-ALL by the HOX gene expression (in particular HOXA3, HOXB3, HOXA4). Like in AML, expression pattern differs also among the major cytogenetical subgroups of ALL. On the other hand, within the BCP-ALL subgroup, no expression difference was found between patients with good (PGR) and poor (PPR) response to the initial steroid therapy which is known to be an excellent predictor of outcome. HOX genes of interest emerged from our analysis: low expression of HOXA7 in hyperdiploid ALL, highly expressed HOXB7 in TEL/AML1-positive ALL and specifically downregulated CDX2 in BCR/ABL-positive ALL. Age-related differences in expression in MLL/AF4-positive ALL seem to link the expression pattern rather with the relative maturity of the cell undergoing (pre)malignant transformation than with the specific changes caused by the leukemogenesis itself. This hypothesis must be tested in comparison to the HOX genes expression in sorted subtypes of normal T and B precursors. This work was supported by MSM0021620813, IGA NR/9526 and GACR 301/08/P532. Disclosures No relevant conflicts of interest to declare.

Glutathione S-transferase theta 1 expressed in granulosa cells as a biomarker for oocyte quality in age-related infertility

2008 ◽  
Vol 90 (4) ◽  
pp. 1026-1035 ◽  
Author(s):  
Megumu Ito ◽  
Miho Muraki ◽  
Yuji Takahashi ◽  
Misa Imai ◽  
Tohru Tsukui ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Oocyte Quality ◽  
Glutathione S Transferase ◽  
Age Related

scholarly journals Tracheal Diameter Estimates Using Age-Related Formula Versus Radiographic Findings: Which Approximates the Actual Tracheostomy Tube in Pediatric Patients?

2018 ◽  
Vol 33 (2) ◽  
pp. 32-36
Author(s):  
Isaac Cesar S. De Guzman
Keyword(s):  
Endotracheal Tube ◽  
Tracheostomy Tube ◽  
Pediatric Patients ◽  
University Hospital ◽  
Estimation Methods ◽  
Radiographic Findings ◽  
Average Value ◽  
Age Related ◽  
Significant Difference ◽  
The Difference

Objective: To compare actual tracheostomy tube sizes with estimated endotracheal tube sizes using age-related formula and tracheal diameter from preoperative radiographs among pediatric Filipino patients aged 0-18 years old undergoing tracheostomy. Methods: Study Design: Review of records Setting:           Tertiary Private University Hospital in Dasmarinas, Cavite, Philippines Patients:         Pediatric patients regardless of gender, aged 0 to 18 years old, with a preoperative radiograph of the trachea, and who subsequently underwent tracheostomy anytime from January 1, 2007 to December 31, 2016 were considered for inclusion. Radiographs were measured, endotracheal tube sizes were computed using age-related formula, and recorded tracheotomy tube sizes were retrieved. Results: Twenty-two patients (12 males, 10 females) aged 10 months to 18-years-old (median age: 11 years) were included in the study. Mean tube sizes were 6.46mm (+/- 1.492 SD) for age-related formula, 5.67mm (+/- 1.1849 SD) for radiograph-based estimation, and 5.0 for actual tracheostomy tube inserted in each patient. The Bland-Altman plot showed the bias estimate at 0.7913 and the lower and upper limits of agreement at -1.3598 and 2.9423 (confidence level 95% or 2 standard deviations away from the mean). Conclusions: The average value derived from radiograph-based estimation is less than the corresponding average value from age-related formula. There is a significant difference between age-related formula-based estimation and actual tracheostomy tube inserted. Since the range of differences between the two estimation methods is high, these results imply that the bias or the difference between measures from the two methods is not consistent, with the two methods exhibiting very poor agreement. Keywords: Tracheostomy, Intubation, Intra Tracheal, Penlington Formula, Trachea Radiograph Measurement, age related formula for endotracheal tube estimation

scholarly journals Comparison of Drusen Volume Assessed by Two Different OCT Devices

2020 ◽  
Vol 9 (8) ◽  
pp. 2657
Author(s):  
Marco Beck ◽  
Devika S. Joshi ◽  
Lieselotte Berger ◽  
Gerd Klose ◽  
Sandro De Zanet ◽  
...  
Keyword(s):  
Mean Difference ◽  
Age Related Macular Degeneration ◽  
Third Party ◽  
Automated Segmentation ◽  
Swept Source ◽  
Age Related ◽  
Significant Difference ◽  
The Difference ◽  
Manual Correction ◽  
Sd Oct

To compare drusen volume between Heidelberg Spectral Domain (SD-) and Zeiss Swept-Source (SS) PlexElite Optical Coherence Tomography (OCT) determined by manual and automated segmentation methods. Thirty-two eyes of 24 patients with Age-Related Macular Degeneration (AMD) and drusen maculopathy were included. In the central 1 and 3 mm ETDRS circle drusen volumes were calculated and compared. Drusen segmentation was performed using automated manufacturer algorithms of the two OCT devices. Then, the automated segmentation was manually corrected and compared and finally analyzed using customized software. Though on SD-OCT, there was a significant difference of mean drusen volume prior to and after manual correction (mean difference: 0.0188 ± 0.0269 mm3, p < 0.001, corr. p < 0.001, correlation of r = 0.90), there was no difference found on SS-OCT (mean difference: 0.0001 ± 0.0003 mm3, p = 0.262, corr. p = 0.524, r = 1.0). Heidelberg-acquired mean drusen volume after manual correction was significantly different from Zeiss-acquired drusen volume after manual correction (mean difference: 0.1231 ± 0.0371 mm3, p < 0.001, corr. p < 0.001, r = 0.68). Using customized software, the difference of measurements between both devices decreased and correlation among the measurements improved (mean difference: 0.0547 ± 0.0744 mm3, p = 0.02, corr. p = 0.08, r = 0.937). Heidelberg SD-OCT, the Zeiss PlexElite SS-OCT, and customized software all measured significantly different drusen volumes. Therefore, devices/algorithms may not be interchangeable. Third-party customized software helps to minimize differences, which may allow a pooling of data of different devices, e.g., in multicenter trials.

scholarly journals Light-induced Nrf2−/− mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kai Wang ◽  
Min Zheng ◽  
Kaitlyn Lee Lester ◽  
Zongchao Han
Keyword(s):  
Animal Model ◽  
Macular Degeneration ◽  
Water Soluble ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Treatment Technique ◽  
Glycol Chitosan ◽  
Injectable Hydrogel ◽  
Age Related ◽  
Ros Accumulation

Abstract Elevated oxidative stress and associated reactive oxygen species (ROS) accumulation are hallmarks in the induction and progression of age-related macular degeneration (AMD). By exposing nuclear factor erythroid 2-related factor (Nrf2) knockout (Nrf2−/−) mice to mild white light, we were able to generate a new dry-AMD like murine model to the study. This animal model developed phenotypes of photoreceptor degeneration, retinal function impairment, ROS accumulation, and inflammation reaction in a relatively shorter time. In the treatment of this animal model we utilized an antioxidative and water soluble nanoparticle known as glycol chitosan coated cerium oxide nanoparticles (GCCNP). The delivery of GCCNP protected retina against progressive retinal oxidative damage. Further combination of GCCNP with alginate-gelatin based injectable hydrogel provided synergistic antioxidant effects and achieved a more rapid recovery of the retinal pigment epithelium and photoreceptor cells. This combined treatment technique has the potential to translate into a clinical intervention for the treatment of AMD.

scholarly journals Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders

2020 ◽  
Author(s):  
Yan Gong ◽  
Jesse Li-Ling ◽  
Dongsheng Xiong ◽  
Jiajing Wei ◽  
Taiqing Zhong ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Oocyte Retrieval ◽  
Ovarian Response ◽  
Oocyte Quality ◽  
Enzyme Linked Immunosorbent Assay ◽  
Altered Expression ◽  
Age Related ◽  
Tertiary Teaching ◽  
Poor Ovarian Responders

Abstract Background: Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment.Methods: A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35-40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.Results: Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P < 0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P < 0.05), showing a trend of decline along with age. Conclusions: For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined with increased age and in accompany with poorer oocyte quality and IVF outcome.

scholarly journals IRX3 and IRX5 collaborate during ovary development and follicle formation to establish responsive granulosa cells in the adult mouse†

2020 ◽  
Vol 103 (3) ◽  
pp. 620-629
Author(s):  
Anqi Fu ◽  
Megan L Koth ◽  
Ryan M Brown ◽  
Sarah A Shaw ◽  
Linda Wang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Granulosa Cells ◽  
Expression Patterns ◽  
Primordial Follicle ◽  
Oocyte Quality ◽  
Ovary Development ◽  
Double Knockout ◽  
Specific Expression ◽  
Two Factors ◽  
And Function

Abstract Healthy development of ovarian follicles depends on appropriate interactions and function between oocytes and their surrounding granulosa cells. Previously, we showed that double knockout of Irx3 and Irx5 (Irx3/5 DKO) in mice resulted in abnormal follicle morphology and follicle death. Further, female mouse models of individual Irx3 or Irx5 knockouts were both subfertile but with distinct defects. Notably, the expression profile of each gene suggests independent roles for each; first, they are colocalized in pre-granulosa cells during development that then progresses to include oocyte expression during germline nest breakdown and primordial follicle formation. Thereafter, their expression patterns diverge between oocytes and granulosa cells coinciding with the formulation and maturation of intimate oocyte–granulosa cell interactions. The objective of this study was to investigate the contributions of Irx5 and somatic cell-specific expression of Irx3 during ovarian development. Our results show that Irx3 and Irx5 contribute to female fertility through different mechanisms and that Irx3 expression in somatic cells is important for oocyte quality and survival. Based on evaluation of a series of genetically modified mouse models, we conclude that IRX3 and IRX5 collaborate in the same cells and then in neighboring cells to foster a healthy and responsive follicle. Long after these two factors have extinguished, their legacy enables these intercellular connections to mature and respond to extracellular signals to promote follicle maturation and ovulation.

Sign in / Sign up

Export Citation Format

Share Document