Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age

2014 ◽  
Vol 26 (8) ◽  
pp. 1072 ◽  
Author(s):  
Leanne Pacella-Ince ◽  
Deirdre L. Zander-Fox ◽  
Michelle Lane
Keyword(s):  
Follicular Fluid ◽  
Ovarian Reserve ◽  
Protein Function ◽  
Maternal Age ◽  
Cumulus Cells ◽  
Advanced Maternal Age ◽  
Oocyte Quality ◽  
Carbamoyl Phosphate ◽  
Protein Activity

Women with reduced ovarian reserve or advanced maternal age have an altered metabolic follicular microenvironment. As sirtuin 5 (SIRT5) senses cellular metabolic state and post-translationally alters protein function, its activity may directly impact on oocyte viability and pregnancy outcome. Therefore, we investigated the role of SIRT5 in relation to ovarian reserve and maternal age. Women (n = 47) undergoing routine IVF treatment were recruited and allocated to one of three cohorts based on ovarian reserve and maternal age. Surplus follicular fluid, granulosa and cumulus cells were collected. SIRT5 mRNA, protein and protein activity was confirmed in granulosa and cumulus cells via qPCR, immunohistochemistry, western blotting and desuccinylation activity. The presence of carbamoyl phosphate synthase I (CPS1), a target of SIRT5, was investigated by immunohistochemistry and follicular-fluid ammonium concentrations determined via microfluorometry. Women with reduced ovarian reserve or advanced maternal age had decreased SIRT5 mRNA, protein and desuccinylation activity in granulosa and cumulus cells resulting in an accumulation of follicular-fluid ammonium, presumably via alterations in activity of a SIRT5 target, CPS1, which was present in granulosa and cumulus cells. This suggests a role for SIRT5 in influencing oocyte quality and IVF outcomes.

131. SIRT3 IN OVARIAN CELLS IS ALTERED BY MATERNAL AGE AND OVARIAN RESERVE

2010 ◽  
Vol 22 (9) ◽  
pp. 49
Author(s):  
L. Pacella ◽  
D. Zander-Fox ◽  
T. Hussein ◽  
T. Fullston ◽  
M. Lane
Keyword(s):  
Gene Expression ◽  
Ovarian Reserve ◽  
Maternal Age ◽  
Cumulus Cells ◽  
Cell Types ◽  
Advanced Maternal Age ◽  
Cellular Functions ◽  
Protein Levels ◽  
Ovarian Cells ◽  
The Impact

Maternal age and reduced AMH levels affect the follicular environment and consequently oocyte viability. The Sirtuin family of protein deacetylases are able to regulate various cellular functions involved in the ageing process in other tissues. In particular, SIRT3 is related to longevity in several cell types and regulates mitochondrial function, however, its presence and role in ovarian cells remains unknown. This study therefore, investigated the presence of SIRT3 in granulosa and cumulus cells, from patients undergoing IVF, and determined the impact of maternal age and low AMH on SIRT3 levels. Granulosa and cumulus cells were collected from women (n = 36), after informed consent, and classified into 3 groups; A (<35 years, normal AMH), B (>40 years (advanced maternal age), normal AMH) and C (<35 years, low AMH). The presence of SIRT3 was determined by q-PCR (expressed as fold-change) or immunohistochemistry. SIRT3 was present in the ovarian cells of all patients analysed. SIRT3 gene expression was reduced in granulosa cells from women with low AMH (0.67 ± 0.17) compared to women with normal AMH (1.00 ± 0.23; P < 0.05). In cumulus cells, levels were reduced with advanced maternal age (0.81 ± 0.08) compared to women <35 years (1.00 ± 0.22; P < 0.05). SIRT3 protein co-localised with mitochondria in the ovarian cells, confirming previous findings for other cell types. In comparison to women <35 years with normal AMH, image analysis determined that SIRT3 protein levels were significantly reduced in the granulosa and cumulus cells from women of advanced maternal age by 21.4% and 31.8% and in women with low AMH by 34.1% and 47.2% respectively. This is the first study to demonstrate SIRT3 presence in human ovarian cells. The observation that SIRT3 levels are altered by advanced maternal age or low AMH (reduced ovarian reserve) implicate its role in ovarian ageing and plausibly in the decrease in oocyte viability observed in these women.

scholarly journals Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve

Reproduction ◽  
2017 ◽  
Vol 153 (4) ◽  
pp. 443-451 ◽  
Author(s):  
Jing Tong ◽  
Shile Sheng ◽  
Yun Sun ◽  
Huihui Li ◽  
Wei-Ping Li ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Ovarian Reserve ◽  
Poor Response ◽  
Oocyte Quality ◽  
Radical Scavenger ◽  
Ivf Outcomes ◽  
Response Group

Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality. Melatonin exerts its antioxidant actions as a strong radical scavenger that might affect oocyte quality directly as it is the most potent antioxidant in follicular fluid. To investigate the precise role of endogenous melatonin in IVF outcomes, we recruited 61 women undergoing treatment cycles of IVF or intracytoplasmic sperm injection (ICSI) procedures and classified them into three groups according to their response to ovarian stimulation. Follicular fluid was collected to assess melatonin levels using a direct RIA method. We found good correlations between melatonin levels in follicular fluid with age, anti-Müllerian hormone (AMH) and baseline follicle-stimulating hormone (bFSH), all of which have been used to predict ovarian reserve. Furthermore, as melatonin levels correlated to IVF outcomes, higher numbers of oocytes were collected from patients with higher melatonin levels and consequently the number of oocytes fertilized, zygotes cleaved, top quality embryos on D3, blastocysts obtained and embryos suitable for transplantation was higher. The blastocyst rate increased in concert with the melatonin levels across the gradient between the poor response group and the high response group. These results demonstrated that the melatonin levels in follicular fluid is associated with both the quantity and quality of oocytes and can predict IVF outcomes as well making them highly relevant biochemical markers of ovarian reserve.

117 Subclinical Mastitis Reduces Ovulation and Oocyte Quality in Milk-Producing Cows

2018 ◽  
Vol 30 (1) ◽  
pp. 198
Author(s):  
G. Santos ◽  
M. P. Bottino ◽  
M. B. D. Ferreira ◽  
J. C. Silveira ◽  
A. C. F. C. M. Avila ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Target Genes ◽  
Bos Taurus ◽  
Bos Indicus ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Subclinical Mastitis ◽  
Oocyte Quality ◽  
Ovulation Rate ◽  
Follicular Dynamics

The aim was to evaluate the effect of subclinical mastitis by somatic cell count (SCC) on follicular dynamics, ovulation, oocyte and cumulus cell quality, exosome size and concentration in milk-producing cows. Crossbred cows (Bos taurus × Bos indicus; that is, Holstein × Gyr) were randomly allocated to control (SCC <200,000 cells mL−1] and mastitis (SCC >400,000 cells mL−1) groups. In experiment 1 (follicular dynamics), cows (n = 57) were submitted to ultrasonographic evaluations every 24 h, after removal of an intravaginal progesterone device (Day 8) up to Day 10. From Day 10, ultrasound evaluations were performed every 12 h, until ovulation or until 96 h after progesterone device withdrawal, in order to follow final dominant follicle growth and ovulation. In experiment 2 (oocyte, cumulus cells, and follicular fluid evaluation), cows (n = 23) were submitted to follicular aspirations, preceded by synchronization of the emergence of the follicular wave. The levels of target genes in cumulus cells (BCL2, BAX, PI3K, PTEN, FOXO3) were evaluated by RT-qPCR. In the follicular fluid, the exosomes were isolated for evaluation of particle size. Data were analysed by the Glimmix procedure of SAS (SAS Institute Inc., Cary, NC, USA). Ovulation rate (P = 0.09) was higher in control cows [control 77.42% (24/31) and mastitis 57.69% (15/26)]. Viable oocyte rate (P = 0.01) was also higher in control cows [control 59.1% (130/220) and mastitis 41.9% (125/298)]. The dynamics of follicular growth did not differ between groups. The number of degenerate oocytes (P = 0.001) was higher in cows of the mastitis group. In the evaluation of cumulus cell gene expression, there was a higher abundance of BAX transcripts (P = 0.003) in cells of mastitis cows. Additionally, the mean and mode of exosome diameter in mastitis cows were smaller (P = 0.03 and P = 0.02, respectively). In conclusion, ovulation rate, oocyte quality, and follicular fluid exosome diameter were lower in cows with subclinical mastitis, demonstrating a link between mammary gland sanitary status and reproduction.

scholarly journals Sirt2-BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality

Aging Cell ◽  
2017 ◽  
Vol 17 (1) ◽  
pp. e12698 ◽  
Author(s):  
Danhong Qiu ◽  
Xiaojing Hou ◽  
Longsen Han ◽  
Xiaoyan Li ◽  
Juan Ge ◽  
...  
Keyword(s):  
Maternal Age ◽  
Advanced Maternal Age ◽  
Oocyte Quality

The role of advanced maternal age and newborn sex in pregnancy outcome

2013 ◽  
Vol 3 (4) ◽  
pp. 159-164 ◽  
Author(s):  
Alessandro Favilli ◽  
Silvia Pericoli ◽  
Gian Carlo Di Renzo ◽  
Sandro Gerli
Keyword(s):  
Pregnancy Outcome ◽  
Maternal Age ◽  
Advanced Maternal Age ◽  
In Pregnancy

126 Interference of mastitis with ovulation and oocyte and granulosa cell quality in dairy cows

2019 ◽  
Vol 31 (1) ◽  
pp. 188
Author(s):  
G. Santos ◽  
M. P. Bottino ◽  
A. P. C. Santos ◽  
R. E. Orlandi ◽  
L. M. S. Simões ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Follicular Fluid ◽  
Rate Control ◽  
Cumulus Cell ◽  
Transcript Abundance ◽  
Cumulus Cells ◽  
Subclinical Mastitis ◽  
Oocyte Quality ◽  
Ovulation Rate ◽  
Intravaginal Device

The objective of this study was to evaluate the effect of mastitis diagnosed by somatic cell count (SCC) on follicular growth, ovulation, oocytes and cumulus cells quality and the concentration and size of exosomes in follicular fluid of dairy cows. In the study, crossbred cows (Bos taurus-Holstein×Bos indicus-Gir) were classified for analysis as control (SCC &lt;200.000 cells mL−1) and mastitis (SCC &gt;400.000 cells mL−1) groups. In Experiment 1 (follicular dynamics), cows (n=57: control=31; mastitis=26) received a progesterone intravaginal device (Sincrogest®, Ourofino Saude Animal, Cravinhos, Brazil) and 2mg of oestradiol benzoate (Sincrodiol®, Ourofino Saude Animal) injected IM. Eight days later (D8), the progesterone device was removed and cows received IM 500mg of cloprostenol (Sincrocio®, Ourofino Saude Animal), 1mg of oestradiol cypionate (SincroCP®, Ourofino Saude Animal) and 300IU of eCG (SicroeCG®, Ourofino Saude Animal). Ultrasound exams (Mindray 4900, probe linear de 5MHz, Shenzhen, China) were performed every 24h from removal of the progesterone-releasing intravaginal device (D8) until 48h later. Thereafter, evaluations were performed every 12h, until ovulation or up to 96h after removal of the progesterone-releasing intravaginal device. In Experiment 2 (oocyte, cumulus complexes, and follicular fluid evaluation), cows (n=26: control=13; mastitis=13) were submitted to follicular aspiration (ovum pickup) for oocyte quality and cumulus cells transcript evaluation. Transcript abundance of apoptosis markers (BCL2, BAX, PI3K, PTEN, FOXO3) was determined by real-time RT-PCR. Moreover, 7 days after the ovum pickup session, the dominant follicle was aspirated and follicular fluid samples were obtained. Exosomes were isolated from the follicular fluid by serial centrifugations, which were also performed for evaluation of particle size and concentration. Statistical analyses were performed using the SAS (SAS Institute Inc., Cary, NC, USA), and the GLIMMIX procedure was used to determine significant differences between groups. Gene expression and exosome data were submitted to the Student’s t-test. Ovulation rate [control 77.4% (24/31) and mastitis 57.7% (15/26); P=0.09] and viable oocytes rate [control 59.1% (130/220) and mastitis 41.9% (125/298); P=0.01] were higher in control animals. Additionally, there was a greater number of degenerate oocytes (control 6.7±1.2 and mastitis 13.3±5.5; P=0.001) in subclinical mastitis cows. There was greater abundance (P=0.003) of BAX cumulus cell transcripts and exosome mean (P=0.03) was smaller in subclinical mastitis cows. However, BCL2, PI3K, PTEN, nd FOXO3 cumulus cell transcripts was similar between treatments. In conclusion, ovulation rate, oocyte quality, and exosome diameter were smaller in cows with SCC &gt;400.000 cells mL−1, demonstrating that subclinical mastitis can influence the fertility of dairy cows.

Role of maternal and paternal age in an assisted reproductive program

2002 ◽  
Vol 55 (11-12) ◽  
pp. 535-538
Author(s):  
Dunja Tabs ◽  
Nebojsa Radunovic
Keyword(s):  
Assisted Reproduction ◽  
Ovarian Reserve ◽  
Maternal Age ◽  
Low Dose ◽  
Reproductive Age ◽  
Paternal Age ◽  
Parental Age ◽  
Younger Women ◽  
Poor Ovarian Reserve

Introduction Many infertile couples try to become parents spontaneously, neglecting the possibility to conceive artificially, so they seek medical help in their late reproductive age. Maternal age Major aspects of maternal age in regard to assisted reproduction consider oocytes, ovaries and endometrium. Also, some habits and maternal diseases associated with aging may have an impact on fertility (smoking, atherosclerosis, previous gynecological operations etc.). Even though estimating the ovarian reserve is the most objective test in assessing female fertility, it has a limited predictive value in younger women. A short protocol of ovulation induction showed best results in women with poor ovarian reserve, but recent studies recommend low-dose gonadotropin-releasing hormone agonists in these cases. Paternal age With aging, sperm parameters become worse, which points to the neglected role of the father in assisted reproduction. Conclusion Thus, parental age plays an important role in assisted reproductive programs.

Anti-Mullerian hormone and its predictive value for assessing oocyte quality

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (6) ◽  
pp. 21-26
Author(s):  
Natalia V. Aleksandrova
Keyword(s):  
Ovarian Reserve ◽  
Predictive Value ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Laboratory Markers ◽  
Diagnostic Capabilities ◽  
First Time

The article systematizes information on the diagnostic capabilities of modern clinical and laboratory markers of ovarian reserve. The diagnostic capabilities of anti-Mllerian hormone (AMH) as a marker of ovarian reserve are discussed, which make it possible to adjust the dose of hormonal drugs and predict the response of the ovary to stimulation in programs of assisted reproductive technologies. This paper discusses for the first time the role of AMH in assessing the quality of oocytes and subsequent embryos. Despite insufficient literature data, further study of AMH, as well as full-scale research in this direction, seems to be extremely promising.

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