scholarly journals Theaflavin 3, 3 ′ -Digallate Delays Ovarian Aging by Improving Oocyte Quality and Regulating Granulosa Cell Function

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Jiahuan He ◽  
Guidong Yao ◽  
Qina He ◽  
Tongwei Zhang ◽  
Huiying Fan ◽  
...  

Ovarian aging refers to the gradual decline of ovarian function with increasing physiological age, manifested as decreased ovarian reserve, elevated aging-related markers, and reduced oocyte quality. With a declining female fertility and a growing aging population, it is urgent to delay ovarian aging to maintain fertility and improve the life quality of women. Theaflavin 3, 3 ′ -digallate (TF3) is a naturally bioactive polyphenol compound extracted from black tea, and its antioxidant properties play an important role in maintaining human health and delaying aging; however, the effects of TF3 on female reproduction and ovarian function are not yet clear. Here, we show that TF3 can preserve primordial follicle pool, partially restore the estrous cycle, and increase the offspring number of aged mice. Meanwhile, TF3 gavage increased the number of oocytes retrieved, decreased the level of reactive oxygen species, increased the level of glutathione, and decreased the abnormal rate of oocyte spindle after ovulation induction. Moreover, TF3 inhibited human granulosa cell apoptosis and improved their antioxidative stress ability. High-throughput sequencing and small-molecule-targeted pharmacological prediction show that TF3 affects multiple pathways and gene expression levels, mainly involved in reproductive and developmental processes. It may also affect cellular function by targeting mTOR to regulate the autophagic pathway, thereby delaying the process of ovarian aging. This study shows that TF3 can be used as a potential dietary supplement to protect ovary function from aging and thereby improving the life quality of advanced-age women.

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yonghui Jiang ◽  
Huangcong Shi ◽  
Yue Liu ◽  
Shigang Zhao ◽  
Han Zhao

Oxidative stress has been recognized as one of the causal mediators of female infertility by affecting the oocyte quality and early embryo development. Improving oxidative stress is essential for reproductive health. Melatonin, a self-secreted antioxidant, has a wide range of effects by improving mitochondrial function and reducing the damage of reactive oxygen species (ROS). This minireview illustrates the applications of melatonin in reproduction from four aspects: physiological ovarian aging, vitrification freezing, in vitro maturation (IVM), and oxidative stress homeostasis imbalance associated with polycystic ovary syndrome (PCOS), emphasising the role of melatonin in improving the quality of oocytes in assisted reproduction and other adverse conditions.


2015 ◽  
Vol 27 (6) ◽  
pp. 969 ◽  
Author(s):  
Neha Garg ◽  
David A. Sinclair

Fertility is the first biological process to break down during aging, thereby making it a useful tool to understand fundamental processes of aging. Reproductive aging in females is associated with a loss of ovarian function characterised by a reduction in the number and quality of oocytes. The central dogma, namely that females are born with a fixed pool of oocytes that progressively decline with increasing maternal age, has been challenged by evidence supporting postnatal oogenesis in mammals. Reports demonstrating formation of new oocytes from newly discovered germline stem cells, referred to as oogonial stem cells (OSCs), has opened new avenues for treatment of female infertility. In this review we discuss why the OSCs possibly lose their regenerative potential over time, and focus specifically on the aging process in germline stem cells as a possible mechanism for understanding female age-related infertility and how we can slow or delay ovarian aging.


2021 ◽  
Vol 22 (3) ◽  
pp. 1371
Author(s):  
Jan Tesarik ◽  
Maribel Galán-Lázaro ◽  
Raquel Mendoza-Tesarik

This is a short review of the basic molecular mechanisms of ovarian aging, written with a particular focus on the use of this data to improve the diagnostic and therapeutic protocols both for women affected by physiological (age-related) ovarian decay and for those suffering premature ovarian insufficiency. Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes. The correct diagnosis of the molecular mechanisms involved in ovarian aging can serve to design treatment strategies that can slow down ovarian decay and increase the quantity and quality of oocytes that can be obtained for an in vitro fertilization attempt. The available treatment options include the use of antioxidants, melatonin, growth hormones, and mitochondrial therapies. All of these treatments have to be considered in the context of each couple’s history and current clinical condition, and a customized (patient-tailored) treatment protocol is to be elaborated.


2016 ◽  
Vol 23 (3) ◽  
Author(s):  
H. M. Havrylyuk ◽  
O. M. Makarchuk

Recently, it has been noticed a great number of uterine fibroids in women with unrealized reproductive function; moreover, the number of combined forms of hyperplastic processes of the reproductive system in 20-25% of women under 30 years of age and 60% of women over 40 years of age is constantly growing creating a favourable background for cancer. It is also known that women with hyperplastic processes suffer from psycho-emotional disorders both before surgeries and after surgical recovery; many of them are diagnosed with adjustment disorder. As many researches note, the main psychotherapeutic aspects include passive view of life, increased anxiety, tendency to dependent behaviour, rejection of own body, protective behaviour and problems with self-assessment. It should also be noted that a comprehensive study of clinical and laboratory data and subjective criteria of life quality is essential in assessment of the feasibility of hysterectomy in women of reproductive age, even if they do not plan to bear children in the future. The objective of the research was to estimate life quality as well as to improve the system of dispensary observation and rehabilitation of women who underwent uterine surgery.Materials and methods. There was performed a comprehensive examination and surgical treatment of 60 women of reproductive age with uterine fibroid who underwent hysterectomy with preservation of appendages. We used modern high quality endocrinological and instrumental techniques. The assessment of the received data was made immediately after surgery, 6 and 2 months, 3 and 5 years after surgery. Quality of life was studied on the basis of a comprehensive assessment using the modified scale of the Nottingham Health Profile and the study of such important indicators as energy, sleep, emotional reactions, social isolation, physical activity, pain. All statistical analysis was performed using a standard package “Statistica for Windows – 6.0”.Results and discussion. On the basis of anamnestic data of patients we revealed health deterioration with high rates of liver and gastrointestinal tract disorders, metabolic disturbances (obesity, hypertensive disorders, fibrocystic breast disease), metabolic-endocrine changes and surgery. Reproductive health in women with uterine fibroid was characterized by long establishment of regular menstrual cycle, its breach in the period of puberty, inflammatory diseases of the genital organs, benign ovarian tumours and their surgical removal, inadequate reproductive behaviour with absent or delayed implementation of reproductive function and induced abortion. 12 months and especially 5 years after surgery there was noticed a progressive deterioration of the ovarian function, which was reflected as the reduction in their volume due to the reduction in the number and size of follicles, deterioration of blood supply to the ovaries, decreased blood flow in the internal iliac artery basin. It should also be noted the progressive hypestrogenism; in addition, there was a clear correlation with the age of the woman, who underwent surgical operation. Changes in life quality of patients with hyperplastic processes of the uterus were manifested in the postoperative period as follows: a decrease in physical activity (43.33% of cases), increased sexual dysfunction (36.66%), inhibition of mental state, conflict-orientated social behaviour, weakening of role functions and subjective deterioration of health and life quality (51.66% of cases).Conclusions. Thus, surgery on uterine fibroids with total or subtotal hysterectomy contributes to interference in a complex neuroendocrine interaction between hypothalamus, pituitary, ovaries, adrenal cortex, thyroid gland and affects the blood supply, innervation, and lymph efflux in the pelvic floor; therefore, postoperative syndromes are polyglandular and polysystemic. Long-term effects after surgery are accompanied by progressive hypestrogenism, decrease in the ovarian function (the reduction in their volume observed during ultrasound examination), reduction in the number and size of follicles, deterioration of blood supply to the ovaries, low blood supply to the internal iliac artery basin.


2004 ◽  
Vol 16 (9) ◽  
pp. 220
Author(s):  
R. L. Robker ◽  
W. V. Ingman ◽  
S. A. Robertson

Transforming Growth Factor β1 (TGFβ1) is essential for normal female reproduction. Mice with a targeted deletion in the TGFβ1 gene (TGFβ1–/–) have severely impaired fertility with pregnancy occurring in <25% of mated females. TGFβ1 is implicated in several aspects of ovarian function, including potentiation of granulosa cell proliferation and suppression of luteal cell apoptosis. Our initial observations indicate that estrous cycling is disrupted in TGFβ1–/– mice and that ovulation rate is reduced. To further investigate how impaired ovarian function contributes to the infertility of TGFβ1–/– mice, ovaries were isolated from TGFβ1+/+ and TGFβ1–/– littermates at proestrus and fixed and sectioned for examination of follicle morphology and growth. BrdU labelling was performed to detect granulosa cell proliferation and blood samples were obtained for analysis of gonadotrophins and ovarian steroid hormones. Histological examination showed that ovaries from TGFβ1–/– mice were smaller than those of TGF–1+/+ mice, however large antral follicles were observed, indicating that TGFβ1 is not essential for granulosa cell proliferation. Compared to TGFβ1+/+ ovaries however, there were fewer antral follicles and only rare corpora lutea. Interestingly, in some cases there were large numbers of macrophages surrounding small follicles suggesting increased follicular atresia and/or altered macrophage activity in the TGFβ1–/– ovaries. Ovaries and serum were also isolated from females at d4 post-coital for assessment of corpora lutea morphology. TGFβ1–/– ovaries weighed less and had fewer corpora lutea than TGFβ1+/+ ovaries. TGFβ1–/– corpora lutea also contained increased numbers of apoptotic cells and infiltrating macrophages indicative of premature luteal regression. Circulating progesterone levels were reduced in TGFβ1–/– females, as was progesterone production per corpus luteum further indicating a functional defect in luteal maintenance. Cumulatively these observations show that TGFβ1 has essential roles in regulation of ovarian macrophage populations, in normal follicular development and in the generation, maintenance and steroidogenic function of corpora lutea.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
G. Simi ◽  
A. R. Genazzani ◽  
M. E. R. Obino ◽  
F. Papini ◽  
S. Pinelli ◽  
...  

Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.


2020 ◽  
Vol 32 (3) ◽  
pp. 292 ◽  
Author(s):  
Saeideh Hasani Azami ◽  
Hamid Nazarian ◽  
Mohammad Amin Abdollahifar ◽  
Fatemeh Eini ◽  
Mehdi Allahbakhshian Farsani ◽  
...  

Reproductive senescence is accompanied by a reduced number and quality of ovarian follicles in response to the accumulation of free radicals and the process of apoptosis. Having selected mice as models, we examined the hypothesis that curcumin as an antioxidant and anti-inflammatory agent might prevent or retard ovarian aging. Female NMRI 21-day-old mice were divided into control, vehicle and curcumin groups. In the treatment group the mice received curcumin at 100mgkg–1day–1 intraperitoneally. After 6, 12 and 33 weeks several parameters were examined including ovarian reserve, oocyte quality, oxidative status, invitro fertilisation and expression of ovulation-related (growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15)) and anti-aging-related (sirtuin 1 (SIRT-1) and SIRT-3) genes. Curcumin treatment up to 12 and 33 weeks resulted in increased ovarian volume and number of follicles and was associated with elevated anti-Müllerian hormone and oestrogen and diminished FSH serum levels. Furthermore, enhanced oocyte maturation, fertilisation and embryo development plus reduced oxidative stress were seen in the curcumin group. Also, the expression of GDF-9, BMP-15, SIRT-1 and SIRT-3 genes was increased in the curcumin group. Concerning gestational age, the findings of the study suggested that administration of curcumin could delay the process of oocyte aging in a mouse model.


Author(s):  
Carolina Lliberos ◽  
Seng H. Liew ◽  
Ashley Mansell ◽  
Karla J. Hutt

Ovarian aging is a natural process characterized by follicular depletion and a reduction in oocyte quality, resulting in loss of ovarian function, cycle irregularity and eventually infertility and menopause. The factors that contribute to ovarian aging have not been fully characterized. Activation of the NLRP3 inflammasome has been implicated in age-associated inflammation and diminished function in several organs. In this study, we used Asc−/− and Nlrp3−/− mice to investigate the possibility that chronic low-grade systemic inflammation mediated by the inflammasome contributes to diminished ovarian reserves as females age. Pro-inflammatory cytokines, IL-6, IL-18, and TNF-α, were decreased in the serum of aging Asc−/− mice compared to WT. Within the ovary of reproductively aged Asc−/− mice, mRNA levels of major pro-inflammatory genes Tnfa, Il1a, and Il1b were decreased, and macrophage infiltration was reduced compared to age-matched WT controls. Notably, suppression of the inflammatory phenotype in Asc−/− mice was associated with retention of follicular reserves during reproductive aging. Similarly, the expression of intra-ovarian pro-inflammatory cytokines was reduced, and follicle numbers were significantly elevated, in aging Nlrp3−/− mice compared to WT controls. These data suggest that inflammasome-dependent inflammation contributes to the age-associated depletion of follicles and raises the possibility that ovarian aging could be delayed, and fertile window prolonged, by suppressing inflammatory processes in the ovary.


2012 ◽  
pp. 63-87
Author(s):  
Anh Mai Ngoc ◽  
Ha Do Thi Hai ◽  
Huyen Nguyen Thi Ngoc

This study uses descriptive statistical method to analyze the income and life qual- ity of 397 farmer households who are suffering social exclusion in an economic aspect out of a total of 725 households surveyed in five Northern provinces of Vietnam in 2010. The farmers’ opinions of the impact of the policies currently prac- ticed by the central government and local authorities to give them access to the labor market are also analyzed in this study to help management officers see how the poli- cies affect the beneficiaries so that they can later make appropriate adjustments.


2020 ◽  
pp. 33-38
Author(s):  
E. Yu. Gan ◽  
L. P. Evstigneeva

Purpose of the study. Assessing the association between the life quality of patients with Sjogren’s Disease and ongoing therapy with various disease-modifying antirheumatic drugs.Material and methods. The study was conducted on the basis of the regional rheumatology center of the consultative diagnostic clinic of the Sverdlovsk Regional Clinical Hospital No. 1. This work is based on the results of a simultaneous study of 74 patients with primary Sjogren’s Disease (SD), distributed in three comparison groups receiving various disease-modifying antirheumatic drugs chlorambucil, methotrexate and hydroxychloroquine. The diagnosis of SD was carried out according to European-American criteria AECGC (2002) [18]. In order to analyze the quality of life of patients with SD, the 36-Item Short Form Health Survey (SF‑36) was used. Statistical data processing was carried out using Statistica 7.0 program.Results. Assessment of the quality of life of patients with SD, which is an integrative criterion of human health and well-being, revealed the absence of statistically significant differences (p > 0.05) on eight scales and two health components of the SF‑36 questionnaire in the analyzed groups that differ in the treatment of disease-modifying antirheumatic drugs chlorambucil, methotrexate and hydroxychloroquine.Conclusions. The obtained data indicate an equivalent quality of life in SD patients treated with different disease-modifying antirheumatic drugs methotrexate, chlorambucil and hydroxychloroquine, and therefore hydroxychloroquine can be considered as an alternative basic therapy in patients with SD with certain limitations and contraindications methotrexate and chlorambucil.


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