scholarly journals Lack of effect of short-term DHEA supplementation on the perimenopausal ovary†

2020 ◽  
Vol 103 (6) ◽  
pp. 1209-1216
Author(s):  
Selva L Luna ◽  
Donald I Brown ◽  
Steven G Kohama ◽  
Henryk F Urbanski

Abstract Dehydroepiandrosterone (DHEA) hormonal supplementation can improve oocyte quality in women with diminished ovarian function. However, it is unclear whether DHEA supplementation can also enhance ovarian function during the perimenopause (i.e., when the number of follicles in the ovary has undergone a marked reduction). To address this question, we examined the impact of 2.5-months of daily 5-mg oral DHEA supplementation on the number of ovarian follicles and the concentration of anti-Müllerian hormone (AMH) in perimenopausal rhesus macaques. Like women, these long-lived nonhuman primates have ~ 28-day menstrual cycles and eventually undergo menopause. They also show similar age-related neuroendocrine changes, including a marked decrease in circulating concentrations of DHEA and DHEA sulfate (DHEAS). Our experimental design involved the following three groups of animals (N = 6 per group): Young adult (mean age = 11.6 years), Old control (mean age = 23.1 years), and Old DHEA-treated (mean age = 23.5 years). Histological examination of the ovaries revealed a significant age-related decrease in the mean number of primordial follicles despite DHEA supplementation. Moreover, AMH concentrations within the ovaries and circulation, assessed by Western analysis and ELISA, respectively, showed significant age-related decreases that were not attenuated by DHEA supplementation. Taken together, these results fail to show a clear effect of short-term physiological DHEA supplementation on the perimenopausal ovary. However, they do not exclude the possibility that alternative DHEA supplementation paradigms (e.g., involving an earlier start date, longer duration and using pharmacological doses) may extend reproductive potential during aging.

Author(s):  
Natalia Llarena ◽  
Christopher Hine

Abstract Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K/PTEN/AKT/FOXO3 and associated TSC/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1/growth hormone pathway, and transsulfuration/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity.


2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Indu Sharma ◽  
Priti Kumari ◽  
Anuradha Sharma ◽  
Subhas Chandra Saha

Abstract Background COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time. Main body of abstract Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases. Conclusion Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.


Author(s):  
Alexandra E. Peters ◽  
Shandelle J. Caban ◽  
Eileen A. McLaughlin ◽  
Shaun D. Roman ◽  
Elizabeth G. Bromfield ◽  
...  

Accompanying the precipitous age-related decline in human female fertility is an increase in the proportion of poor-quality oocytes within the ovary. The macroautophagy pathway, an essential protein degradation mechanism responsible for maintaining cell health, has not yet been thoroughly investigated in this phenomenon. The aim of this study was to characterize the macroautophagy pathway in an established mouse model of oocyte aging using in-depth image analysis-based methods and to determine mechanisms that account for the observed changes. Three autophagy pathway markers were selected for assessment of gene and protein expression in this model: Beclin 1; an initiator of autophagosome formation, Microtubule-associated protein 1 light chain 3B; a constituent of the autophagosome membrane, and lysosomal-associated membrane protein 1; a constituent of the lysosome membrane. Through quantitative image analysis of immunolabeled oocytes, this study revealed impairment of the macroautophagy pathway in the aged oocyte with an attenuation of both autophagosome and lysosome number. Additionally, an accumulation of amphisomes greater than 10 μm2 in area were observed in aging oocytes, and this accumulation was mimicked in oocytes treated with lysosomal inhibitor chloroquine. Overall, these findings implicate lysosomal dysfunction as a prominent mechanism by which these age-related changes may occur and highlight the importance of macroautophagy in maintaining mouse pre-ovulatory oocyte quality. This provides a basis for further investigation of dysfunctional autophagy in poor oocyte quality and for the development of therapeutic or preventative strategies to aid in the maintenance of pre-ovulatory oocyte health.


2021 ◽  
pp. 1-17
Author(s):  
Enda Du ◽  
Yuetian Liu ◽  
Ziyan Cheng ◽  
Liang Xue ◽  
Jing Ma ◽  
...  

Summary Accurate production forecasting is an essential task and accompanies the entire process of reservoir development. With the limitation of prediction principles and processes, the traditional approaches are difficult to make rapid predictions. With the development of artificial intelligence, the data-driven model provides an alternative approach for production forecasting. To fully take the impact of interwell interference on production into account, this paper proposes a deep learning-based hybrid model (GCN-LSTM), where graph convolutional network (GCN) is used to capture complicated spatial patterns between each well, and long short-term memory (LSTM) neural network is adopted to extract intricate temporal correlations from historical production data. To implement the proposed model more efficiently, two data preprocessing procedures are performed: Outliers in the data set are removed by using a box plot visualization, and measurement noise is reduced by a wavelet transform. The robustness and applicability of the proposed model are evaluated in two scenarios of different data types with the root mean square error (RMSE), the mean absolute error (MAE), and the mean absolute percentage error (MAPE). The results show that the proposed model can effectively capture spatial and temporal correlations to make a rapid and accurate oil production forecast.


2005 ◽  
Vol 64 (2) ◽  
Author(s):  
Alessandro Piccardo ◽  
Luigi Martinelli ◽  
Giancarlo Passerone

Background: The tendency of modern surgery is towards the reduction of invasiveness. The aim of this study is to evaluate the impact of the learning curve, the reliability, the short term results and the advantages in terms of rapid rehabilitation of endoscopic vein harvesting (EVH) in a consecutive series of 20 patients operated on of aorto-coronary bypass surgery. Methods: Between February and June 2005, 20 patients between 61 e 82 years of age underwent EVH with the use of Vasoview® 5 (Guidant Corporation, Indianapolis, USA). To evaluate the impact of learning curve on the total operative time, patients were divided in 4 chronologically consecutive groups (G1, G2, G3, G4). Intraoperative characteristics and short term results were evaluated. Results: The mean velocity and the mean time of harvesting in G4 were 0,68 cm/min and 45 min. respectively, similar to the time required for a scheletonized left internal mammary artery harvesting. In the first 5 patients 2 conversions were required, one of them related to the EVH technique. No bleeding, functional impairment or infective complications are reported. Active mobilization was possible in every case in the first post-operative day. Conclusions: EVH is a reliable technique and the learning curve can be limited to the first 5 cases. The foreseeble reduction of infectious complications, the absence of pain and the immediate mobilization of the leg allow a rapid and effective rehabilitation.


Author(s):  
Patricia M. Lutz ◽  
Matthias J. Feucht ◽  
Judith Wechselberger ◽  
Michael Rasper ◽  
Wolf Petersen ◽  
...  

Abstract Purpose Ultrasound (US) examination of the medial joint space of the knee has played a subordinate diagnostic role up till now. The purpose of the present study was to describe mean values of medial joint width and to investigate the impact of gender, age, and body mass index (BMI) on medial joint laxity in healthy knees using modern, dynamic US in a standardized fashion in unloaded and standardized loaded conditions. Methods A total of 65 subjects with 79 healthy knees were enrolled in this study. All volunteers underwent clinical examination of the knee. The medial knee joint width was determined using US in a supine position at 0° and 30° of knee flexion in unloaded and standardized loaded (= 15 Dekanewton, daN) conditions using a specific device. Mean values were described and correlations between medial knee joint width and gender, age, and BMI were assessed. Results Thirty-two females and 33 males were enrolled in this study. The mean medial joint width in 0° unloaded was 5.7 ± 1.2 mm and 7.4 ± 1.4 mm loaded. In 30° of knee flexion, the mean medial joint width was 6.1 ± 1.1 mm unloaded and 7.8 ± 1.2 mm loaded. The average change between unloaded and loaded conditions in 0° was 1.7 ± 1.0 mm and in 30° 1.7 ± 0.9 mm. A significant difference between genders was evident for medial joint width in 0° and 30° of flexion in unloaded and loaded conditions (p < 0.05). With rising age, a significant increased change of medial joint space width between unloaded and loaded conditions could be demonstrated in 0° (p = 0.032). No significant correlation between BMI and medial joint width in US could be found. Conclusion Mean values of medial joint width in unloaded and standardized loaded conditions using a fixation device could be demonstrated. Based on the results of this study, medial knee joint width in US is gender- and age-related in healthy knees. These present data may be useful for evaluating patients with acute or chronic pathologies to the medial side of the knee. Level of evidence III.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wenlei Ye ◽  
Wei Shen ◽  
Wei Yan ◽  
Su Zhou ◽  
Jing Cheng ◽  
...  

There are about 1-2 million follicles presented in the ovary at birth, while only around 1000 primordial follicles are left at menopause. The ovarian function also decreases in parallel with aging. Folliculogenesis is vital for ovarian function, no matter the synthesis of female hormones or ovulation, yet the mechanisms for its changing with increasing age are not fully understood. Early follicle growth up to the large preantral stage is independent of gonadotropins in rodents and relies on intraovarian factors. To further understand the age-related molecular changes in the process of folliculogenesis, we performed microarray gene expression profile analysis using total RNA extracted from young (9 weeks old) and old (32 weeks old) mouse ovarian secondary follicles. The results of our current microarray study revealed that there were 371 (≥2-fold, q-value ≤0.05) genes differentially expressed in which 174 genes were upregulated and 197 genes were downregulated in old mouse ovarian secondary follicles compared to young mouse ovarian secondary follicles. The gene ontology and KEGG pathway analysis of differentially expressed genes uncovered critical biological functions such as immune system process, aging, transcription, DNA replication, DNA repair, protein stabilization, and apoptotic process were affected in the process of aging. The considerable changes in gene expression profile may have an adverse influence on follicle quality and folliculogenesis. Our study provided information on the processes that may contribute to age-related decline in ovarian function.


2011 ◽  
Vol 301 (2) ◽  
pp. E351-E355 ◽  
Author(s):  
N. D. Shaw ◽  
S. S. Srouji ◽  
S. N. Histed ◽  
J. E. Hall

Recent studies have demonstrated an age-related decline in gonadotropins and a decrease in pituitary responsiveness to GnRH, indicating that aging influences the neuroendocrine components of the female reproductive axis independently of changes in ovarian function. To determine whether aging might also affect the luteinizing hormone (LH) negative and positive feedback responses to gonadal steroids, we administered a controlled, graded sex steroid infusion to 11 younger (45–56 yr) and nine older (70–80 yr) postmenopausal women (PMW) in whom endogenous ovarian steroids and peptides are uniformly low. The doses of estradiol (E2) and progesterone (P) were chosen to mimic levels across the normal follicular phase and have been shown previously to induce negative followed by positive feedback on LH. Similar E2 and P levels were achieved in younger and older PMW ( P = 0.4 and 0.3, respectively) and produced a biphasic LH response in all subjects. The early decline in LH to 53% of baseline was not different in older vs. younger PMW. However, the positive feedback effect was attenuated in older compared with younger PMW (peak LH 144.4 ± 19.5 vs. 226.8 ± 22.3 IU/l, respectively, P = 0.01). In conclusion, these studies in PMW demonstrate preservation of short-term steroid negative and positive feedback in response to exogenous E2 and P with aging. Attenuation of positive feedback in older compared with younger PMW is consistent with previous reports of declining GnRH responsiveness with aging.


Reproduction ◽  
2009 ◽  
Vol 138 (5) ◽  
pp. 793-799 ◽  
Author(s):  
Margaret L Walker ◽  
Daniel C Anderson ◽  
James G Herndon ◽  
Lary C Walker

In female squirrel monkeys (Saimiri sciureus), the reproductive period normally extends from ∼2.5 years to the mid-teens. In the present study, we examined the age-associated cytological changes in the ovaries of 24 squirrel monkeys ranging in age from newborn to ∼20 years. We found a significant, age-related decline in the number of primordial follicles, with the most pronounced loss occurring between birth and 5 years. After ∼8 years of age, relatively few primordial follicles were evident in the ovarian sections examined. An unusual feature of the aging squirrel monkey ovary is the emergence of highly differentiated, encapsulated clusters of granulosa cells that increase in size and number, particularly after the age of 8 years. Many of these cells express anti-Müllerian hormone, and, histologically, the clusters resemble granulosa cell tumors in humans. However, granulosa cell clusters (GCCs) are present in both ovaries of all older squirrel monkeys, and they display no obvious signs of malignancy, suggesting that they are a normal feature of ovarian aging in this species. Our findings indicate that reproductive senescence in female squirrel monkeys, as in other primates, involves the inexorable depletion of ovarian follicles. In addition, the consistent appearance of abundant, well-differentiated clusters of granulosa cells in older squirrel monkeys, prior to the cessation of reproduction, suggests that these structures may influence the later stages of reproductive potential in this species. Analysis of GCCs in older squirrel monkeys also could yield insights into the pathophysiology of granulosa cell tumors in humans.


2021 ◽  
Author(s):  
Abbas Habibalahi ◽  
Michael J. Bertoldo ◽  
Saabah B. Mahbub ◽  
Jared M. Campbell ◽  
Dale M. Goss ◽  
...  

Abstract One of the earliest physiological consequences of advancing age is the loss of female reproductive potential. This is primarily due to oocyte quality and developmental competence, which is highly sensitive to biological age. We applied deep learning, swarm intelligence and discriminative analysis to images of mouse oocytes taken by common bright field microscopy and were successfully able to identify a highly informative deep radiomic signature (DRS) of oocyte age. This signature distinguished morphological changes in oocytes associated with maternal age with 92% accuracy (AUC~1), reflecting this decline in oocyte quality. We then employed the DRS to evaluate the impact of the treatment of reproductively aged mice with the NAD+ precursor nicotinamide mononucleotide (NMN). The DRS signature classified 60% of oocytes from NMN-treated aged mice as having a 'young' morphology, suggesting that NMN was able to rejuvenate the morphological changes identified by the DRS. These findings indicate that NMN therapy may be able to restore the quality of a sizable subset of oocytes affected by reproductive ageing, and that these oocytes will be able to be distinguished and selected by DRS.


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