IMPLICATION OF SIRTUINS AND KISSPEPTIN IN OVARIAN AGING

Цель работы - исследование экспрессии сируинов-1 и -6 и кисспептина в ткани яичников человека, взятых в разные периоды онтогенеза - от формирования пула фолликулов в антенатальном периоде до угасания функции яичников в постменопаузе. Выявлено, что сиртуины экспрессируются в ткани яичника человека во всех возрастных группах. Максимальный уровень экспрессии SIRT1 в ткани яичника наблюдали в периоды внутриутробного развития и перименопаузы, SIRT6 - в репродуктивный период и перименопаузу. Показано участие SIRT1 в пренатальном отборе ооцитов у плодов человека, так как именно в этой группе выявлена повышенная экспрессия данного маркера. Уровень экспрессии маркера кисспептина растет по мере формирования яичников и включения репродуктивной функции, пик экспрессии наблюдается в период перед наступлением климакса. Проведенное исследование по выявлению экспрессии этих белков в яичнике человека расширяет представление о регуляции фолликулярного резерва яичников и репродуктивном старении. The aim of the work was to study the expression of sirtuins 1 and 6 and kisspeptin in human ovarian tissue taken in different periods of ontogenesis: from the formation of a pool of follicles in the antenatal period to the extinction of ovarian function in postmenopausal women. It was revealed that sirtuins are expressed in human ovary tissue in all age groups. The maximum expression level of SIRT1 in ovarian tissue was observed during intrauterine development and during the perimenopause, SIRT6 during the reproductive period and perimenopause. The participation of SIRT1 in prenatal selection of oocytes in human fetuses was shown, since it was in this group that increased expression of this marker was revealed. The expression level of the kisspeptin marker increases with the formation of the ovaries and the inclusion of reproductive function; the peak of expression is observed in the period before the onset of menopause. The study conducted to identify the expression of these proteins in the human ovary expands the understanding of the regulation of the ovarian follicular reserve and reproductive aging.

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Ovarian Tissue Vitrification as a Method for Ovarian Preservation in Women with Cancer: an Analysis of Granulose Cell Apoptosis

KnE Medicine ◽

10.18502/kme.v1i1.532 ◽

2016 ◽

Vol 1 (1) ◽

Author(s):

Budi Wiweko

Keyword(s):

Experimental Study ◽

Cell Apoptosis ◽

Ovarian Function ◽

Ovarian Tissue ◽

Obstetrics And Gynecology ◽

Human Ovary ◽

Primordial Follicles ◽

Quasi Experimental ◽

Function Preservation ◽

The Mean

<p class="ParaAttribute48">The aim of this study was to obtain the effective method of ovarian function preservation with granulose cell apoptosis assessment. Ovarian tissue vitrification became a method for ovarian function preservation in women with cancer. This technique can be done anytime without delay on cancer therapy, in prepubertal and unmarried patient. It also can store many primordial follicles. Ovarian tissue vitrification study is still limited to animal test and there was no data about apoptosis assessment after ovarian vitrification in human ovary. This is a quasi experimental study which was held in Department of Obstetrics and Gynecology Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo General Hospital and Fatmawati Hospital Jakarta from March 2012 to May 2015. Ovaries from thirteen women between 31-37 years of age who underwent oophorectomy with gynecological indication were examined. There were no difference morphologically between follicles from fresh and warmed-vitrified ovaries. The mean protein Bax expression on the fresh ovaries which assessed in the form of H-score was 1,66 ± 0,14 compared to 1,68 ± 0,13 on the warmed-vitrified grup (p = 0,165). The mean protein Bcl-2 expression on the fresh ovaries which assessed in the form of H-score was 1,73 ± 0,10 compared to 1,71 ± 0,10 on the warmed-vitrified grup (p = 0,068). As a conclusion, it was shown that vitrification did not affect Bax and Bcl-2 expression on human ovary.</p>

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The interrelationship between female reproductive aging and survival

The Journals of Gerontology Series A ◽

10.1093/gerona/glab252 ◽

2021 ◽

Author(s):

Jeffrey B Mason ◽

Tracy L Habermehl ◽

Kaden B Underwood ◽

Augusto Schneider ◽

Miguel A Brieño-Enriquez ◽

...

Keyword(s):

Germ Cell ◽

Ovarian Function ◽

Ovarian Tissue ◽

Reproductive Potential ◽

Reproductive Function ◽

Environmental Pressures ◽

Disease Rates ◽

Primitive Species ◽

Female Survival ◽

Disease Risks

Abstract The link between survival and reproductive function is demonstrated across many species and is under both long-term evolutionary pressures and short-term environmental pressures. Loss of reproductive function is common in mammals and is strongly correlated with increased rates of disease in both males and females. However, the reproduction-associated change in disease rates is more abrupt and more severe in women, who benefit from a significant health advantage over men until the age of menopause. Young women with early ovarian failure also suffer from increased disease risks, further supporting the role of ovarian function in female health. Contemporary experiments where the influence of young ovarian tissue has been restored in post-reproductive-aged females with surgical manipulation were found to increase survival significantly. In these experiments, young, intact ovaries were used to replace the aged ovaries of females that had already reached reproductive cessation. As has been seen previously in primitive species, when the young mammalian ovaries were depleted of germ cells prior to transplantation to the post-reproductive female, survival was increased even further than with germ cell-containing young ovaries. Thus, extending reproductive potential significantly increases survival and appears to be germ cell and ovarian hormone-independent. The current review will discuss historical and contemporary observations and theories that support the link between reproduction and survival and provide hope for future clinical applications to decrease menopause-associated increases in disease risks.

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O-002 Expanding the ovary’s reproductive lifespan: Preservation and Rejuvenation

Human Reproduction ◽

10.1093/humrep/deab125.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Pellicer

Keyword(s):

Ovarian Function ◽

Ovarian Tissue ◽

Reproductive Function ◽

Primordial Follicle ◽

Endocrine Function ◽

Ovarian Tissue Cryopreservation ◽

Poor Responders ◽

Hippo Signaling

Abstract Study question The ovary has short lifespan. Genetic and pathologic alterations make it shorter. Moreover, many women delay fertility requiring expanded ovarian function. Can be realistically achieved? Summary answer The reproductive lifespan of the ovary can be expanded to a certain extent in physiologic and pathologic (premature ovarian insufficiency (POI)) conditions. What is known already In ovaries functioning in physiologic conditions, oocyte cryopreservation (OC) is an established method to expand the reproductive lifespan allowing women to postpone fertility without compromising oocyte’s performance. In oncology, ovarian tissue cryopreservation/ ovarian tissue transplantation (OTC/OTT) and OC are widely employed. In POI patients, there are resting follicles in 1/3 of patients. Different techniques have been developed to “awake” these follicles. Some surgical procedures disrupt Hippo signaling to induce primordial follicle growth; , others intend to employ the growth factors contained in blood; some others use bone marrow-derived stem cells to reach similar goals. Study design, size, duration A literature search was done to identify the most recent and informative studies on the different techniques applied to increase the reproductive lifespan of the ovaries, including those clinically available, such as OC, and others still considered experimental, such as OCT/OTT, injection of platelets-enriched plasma (PRP), culture-free in vitro activation(CF-IVA), and autologous stem cell ovarian transplantation (ASCOT). Participants/materials, setting, methods Outcome of 641 healthy women performing OC and ART cycles. In oncology, OC in 80 women and OTC/OTT in 285 patients willing to conceive was analyzed. Both techniques were compared in the same setting in oncology : 1024 undergoing OC and 800 performing OCT. In POI, we analyzed the outcome of 304 women after PRP; 11 undergoing CF-IVA; and 28 ASCOT patients. The most relevant experimental techniques were also analyzed to understand future directions. Main results and the role of chance When it comes to expanding the reproductive function in physiologic conditions, mostly due to delay in childbearing, the follow-up of 641 women out of 1073 who underwent OC and subsequent embryo transfer (ET) has shown 68.8% cumulative live birth rates (C-LBR). Age matters because C-LBR decreased >50% after age 35 yrs. If only the endocrine function of the ovary is considered, OCT/OTT has consistently shown almost 86% efficacy. In Oncology, OC provided 42.1% C-LBR in 80 individuals after cure, while the follow-up of 285 women from 5 different centers after OCT/OTT yield 26% LBR. Both OC and OTT were compared in the same setting and OC proved to be slightly better, with 32.6% LBR as compared to 22.8% in OCT/OTT. Regarding POI, the use of intraovarian PRP injection in 304 women displayed 8% LBR; CF-IVA 36.3% LBR in 11 women; and ASCOT 10% LBR in 10 POI patients and 27.8% in 18 poor responders (PR). Experimental data suggest that a combination of ASCOT and PRP must be the best alternative to activate dormant follicles in POI women. Limitations, reasons for caution: None of the studies was a RCT, and many had not controls, most are descriptive. Regarding oncology patients OC is save and reassuring. The experience shows that OCT/OTT is also safe, although some Scientific Societies label OCT/OTT still as experimental. All the techniques employed in POI are experimental yet. Wider implications of the findings Expanding the reproductive lifespan of the ovary in health and disease (oncology and others) employing OC is a routine; OCT/OTT can be also applied to expand the endocrine function of the ovaries. The best and less invasive method to activate follicles in POI and PR still needs to be defined. Trial registration number NCT02240342; NCT03535480; NCT04475744; NCT02354963

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Ovarian Tissue Vitrification as a Method for Ovarian Preservation in Women with Cancer: an Analysis of Granulose Cell Apoptosis

Indonesian Journal of Obstetrics and Gynecology ◽

10.32771/inajog.v4i2.81 ◽

2016 ◽

pp. 88 ◽

Cited By ~ 3

Author(s):

Budi Wiweko ◽

Huthia Andriyana ◽

Achmad Aulia

Keyword(s):

Cell Apoptosis ◽

Obstet Gynecol ◽

Ovarian Function ◽

Ovarian Tissue ◽

Morphological Difference ◽

Human Ovary ◽

Primordial Follicles ◽

Quasi Experimental ◽

Function Preservation ◽

The Mean

Objective: To obtain the effective method of ovarian function preservation with granulose cell apoptosis assessment. Ovarian tissue vitrification became a method for ovarian function preservation in women with cancer. This technique can be done anytime without delay on cancer therapy both in prepubertal and unmarried patient. It can also store many primordial follicles. Ovarian tissue vitrification study is still limited to animal test and there are no data about apoptosis assessment after ovarian vitrification in human ovary. Method: This quasi experimental study was held in Department of Obstetrics and Gynecology Faculty of Medicine University of Indonesia - Dr. Cipto Mangunkusumo General Hospital and Fatmawati Hospital Jakarta from March 2012 to May 2015. Ovaries from thirteen women between 31 and 37 years old who underwent oophorectomy with gynecological indication were examined. Result: There was no morphological difference between follicles from fresh and warmed-vitrified ovaries. The mean protein Bax expression on the fresh ovaries assessed in the form of H-score was 1.66 (SD 0.14) compared with 1.68 (SD 0.13) on the warmedvitrified group (p=0.165). The mean protein Bcl-2 expression on the fresh ovaries examined in the form of H-score was 1.73 (SD 0.10) compared with 1.71 (SD 0.10) on the warmed-vitrified group (p=0.068). Conclusion: Ovarian tissue vitrification does not affect the Bax and Bcl-2 expression on human ovary. [Indones J Obstet Gynecol 2016; 4-2: 88-92] Keywords: apoptosis, bax, Bcl-2, ovarian tissue vitrification

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Cryopreservation and Fertility: Current and Prospective Possibilities for Female Cancer Patients

ISRN Obstetrics and Gynecology ◽

10.5402/2011/350813 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Jacira Ribeiro Campos ◽

Ana Carolina Japur de Sá Rosa-e-Silva

Keyword(s):

Ovarian Function ◽

Ovarian Tissue ◽

Survival Rates ◽

Reproductive Function ◽

Human Reproduction ◽

Malignant Neoplasms ◽

Assisted Human Reproduction ◽

Female Cancer Patients ◽

Preservation Of Fertility

With the evolution of the treatment of malignant neoplasms, the survival rates of patients undergoing chemo- or radiotherapy are increasing. The continuous development of techniques of assisted human reproduction has led to important strategies in an attempt to maintain reproductive function in patients subjected to treatment of neoplastic diseases, among them cryopreservation of embryos, gametes, and ovarian cortical tissue. The freezing of ovarian tissue is currently being proposed with the primary purpose of preserving ovarian function in these patients. Currently, the major challenge of groups working with preservation of fertility is the use of cryopreserved ovarian tissue after disease remission. The main alternatives presented today are the implantation of hetero- or orthotopic tissue and isolation of immature follicles from ovarian tissue followed by in vitro maturation and assisted reproduction procedures.

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Six children born after 15 ovarian tissue transplantations: the French protocol for the development of ovarian tissue autograft in order to restore ovarian function (DATOR)

10.26226/morressier.5912d9ebd462b80292386329 ◽

2017 ◽

Author(s):

Clotilde Amiot

Keyword(s):

Ovarian Function ◽

Ovarian Tissue

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Ovarian tissue freezing and activation after thawing: an update

Middle East Fertility Society Journal ◽

10.1186/s43043-021-00056-5 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Li-fan Peng

Keyword(s):

Granulosa Cells ◽

Clinical Decision Making ◽

Ovarian Function ◽

Ovarian Tissue ◽

Clinical Decision ◽

The Body ◽

Endocrine Function ◽

Ovarian Tissue Cryopreservation ◽

Main Body ◽

Tissue Cryopreservation

Abstract Background With the growth of women’s age, ovarian failure can be caused by various factors. For the women who need chemotherapy because of cancer factors, the preservation of fertility is more urgent. The treatment of cancer is also a process in which all tissues and organs of the body are severely damaged, especially in the reproductive system. Main body As a new fertility preservation technology, autologous ovarian tissue cryopreservation and transplantation is developing rapidly and showing great potentiality in preserving ovarian endocrine function of young cervical cancer patients. Vitrification and slow freezing are two common techniques applied for ovarian tissue cryopreservation. Thus, cryopreserved/thawed ovarian tissue and transplantation act as an important method to preserve ovarian function during radiotherapy and chemotherapy, and ovarian cryopreservation by vitrification is a very effective and extensively used method to cryopreserve ovaries. The morphology of oocytes and granulosa cells and the structure of organelles were observed under the microscope of histology; the hormone content in the stratified culture medium of granulosa cells with the diameter of follicle was used to evaluate the development potential of ovarian tissue, and finally the ovarian tissue stimulation was determined by the technique of ovarian tissue transplantation. Conclusions Although there are some limitations, the team members still carry out this review to provide some references and suggestions for clinical decision-making and further clinical research.

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Decline of ovarian function in patients with rheumatoid arthritis: serum anti-Müllerian hormone levels in a longitudinal cohort

RMD Open ◽

10.1136/rmdopen-2020-001307 ◽

2020 ◽

Vol 6 (3) ◽

pp. e001307

Author(s):

Jenny Brouwer ◽

Radboud J E M Dolhain ◽

Johanna M W Hazes ◽

Nicole S Erler ◽

Jenny A Visser ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mixed Model ◽

Linear Mixed Model ◽

Ovarian Function ◽

Reproductive Function ◽

Related Factors ◽

Original Cohort ◽

Primordial Follicles ◽

Age At Menopause ◽

Over Time

ObjectiveRheumatoid arthritis (RA) often affects women in their fertile age, and is known to compromise female fertility. Serum anti-Müllerian hormone (AMH) levels are a proxy for the total number of primordial follicles, and a reliable predictor of the age at menopause. Our objective was to study the longitudinal intra-individual decline of serum AMH levels in female RA patients.MethodsFemale RA patients from a nationwide prospective cohort (2002–2008) were re-assessed in 2015–2016. Serum AMH levels were measured using the picoAMH assay and compared with healthy controls. A linear mixed model (LMM) was built to assess the effect of RA-related clinical factors on the decline of AMH levels.ResultsA group of 128 women were re-assessed at an age of 42.6±4.4 years, with a median disease duration of 15.8 (IQR 12.7–21.5) years. The time between first and last AMH assessments was 10.7±1.8 (range 6.4–13.7) years. Participants represented a more fertile selection of the original cohort. At follow-up, 39% of patients had AMH levels below the 10th percentile of controls (95% CI 31% to 48%), compared with 16% (95% CI 9.3% to 22%) at baseline. The LMM showed a significant decline of AMH with increasing age, but no significant effect of RA-related factors on AMH.ConclusionAMH levels in RA patients showed a more pronounced decline over time than expected, supporting the idea that in chronic inflammatory conditions, reproductive function is compromised, resulting in a faster decline of ovarian function over time and probably an earlier age at menopause.

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