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Nature Aging Nov 2021Female ovaries degenerate about 20 years earlier than testes leading to reduced primordial follicle reserve and a reduction in oocyte quality. Here we found that bridge...
Female ovaries degenerate about 20 years earlier than testes leading to reduced primordial follicle reserve and a reduction in oocyte quality. Here we found that bridge integrator 2 (BIN2) is enriched in mouse ovaries and oocytes and that global knockout of this protein improves both female fertility and oocyte quality. Quantitative ovarian proteomics and phosphoproteomics showed that Bin2 knockout led to a decrease in phosphorylated ribosomal protein S6 (p-RPS6), a component of the mammalian target of rapamycin pathway and greatly increased nicotinamide nucleotide transhydrogenase (NNT), the free-radical detoxifier. Mechanistically, we find that phosphorylation of BIN2 at Thr423 and Ser424 leads to its translocation from the membrane to the cytoplasm, subsequent phosphorylation of RPS6 and inhibition of Nnt translation. We synthesized a BIN2-penetrating peptide (BPP) designed to inhibit BIN2 phosphorylation and found that a 3-week BPP treatment improved primordial follicle reserve and oocyte quality in aging and after chemotherapy-induced premature ovarian failure without discernible side effects.
Topics: Female; Mice; Animals; Ovary; Phosphorylation; Signal Transduction; Oocytes; Fertility; Mammals
PubMed: 37118338
DOI: 10.1038/s43587-021-00133-4 -
Environment International Sep 2023Evidence indicates a link between exposure to ambient air pollution and decreased female fertility. The ability of air pollution particles to reach human ovarian tissue...
Evidence indicates a link between exposure to ambient air pollution and decreased female fertility. The ability of air pollution particles to reach human ovarian tissue and follicles containing the oocytes in various maturation stages has not been studied before. Particulate translocation might be an essential step in explaining reproductive toxicity and assessing associated risks. Here, we analysed the presence of ambient black carbon particles in (i) follicular fluid samples collected during ovum pick-up from 20 women who underwent assisted reproductive technology treatment and (ii) adult human ovarian tissue from 5 individuals. Follicular fluid and ovarian tissue samples were screened for the presence of black carbon particles from ambient air pollution using white light generation by carbonaceous particles under femtosecond pulsed laser illumination. We detected black carbon particles in all follicular fluid (n = 20) and ovarian tissue (n = 5) samples. Black carbon particles from ambient air pollution can reach the ovaries and follicular fluid, directly exposing the ovarian reserve and maturing oocytes. Considering the known link between air pollution and decreased fertility, the impact of such exposure on oocyte quality, ovarian ageing and fertility needs to be clarified urgently.
Topics: Adult; Humans; Female; Ovary; Follicular Fluid; Oocytes; Air Pollution; Carbon
PubMed: 37603992
DOI: 10.1016/j.envint.2023.108141 -
Virology Sep 2021Pathogens are transmitted from one host to another either by vertical transmission (VT) or horizontal transmission (HT). Mosquito-borne arboviruses (arthropod-borne...
Pathogens are transmitted from one host to another either by vertical transmission (VT) or horizontal transmission (HT). Mosquito-borne arboviruses (arthropod-borne viruses), including several clinically important viruses such as dengue, Zika, West Nile and chikungunya viruses persist in nature by both VT and HT. VT may also serve as an essential link in the transmission cycle during adverse environmental conditions. VT rates (VTRs) vary between virus families and even among viruses within the same genus. The mechanism behind these differences in VTRs among viruses is poorly understood. For efficient VT to occur, viruses must infect the mosquito germline. Here, we show that Zika virus infects mosquito ovaries and is transmitted vertically at a low rate. The infected progeny derive from mosquitoes with infected ovaries. The prevalence of ovary infection increases after a second non-infectious blood meal following an infectious blood meal.
Topics: Aedes; Animals; Cell Line; Female; Ovary; Viral Plaque Assay; Zika Virus
PubMed: 34147955
DOI: 10.1016/j.virol.2021.06.002 -
Frontiers in Endocrinology 2023Aging leads to a general decline in protective immunity. The most common age-associated effects are in seen T-cell mediated immune function. Adult mice whose immune... (Review)
Review
Aging leads to a general decline in protective immunity. The most common age-associated effects are in seen T-cell mediated immune function. Adult mice whose immune systems show only moderate changes in T-cell subsets tend to live longer than age-matched siblings that display extensive T-cell subset aging. Importantly, at the time of reproductive decline, the increase in disease risks in women significantly outpace those of men. In female mice, there is a significant decline in central and peripheral naïve T-cell subsets at the time of reproductive failure. Available evidence indicates that this naïve T-cell decline is sensitive to ovarian function and can be reversed in post-reproductive females by transplantation of young ovaries. The restoration of naïve T-cell subsets due to ovarian transplantation was impressive compared with post-reproductive control mice, but represented only a partial recovery of what was lost from 6 months of age. Apparently, the influence of ovarian function on immune function may be an indirect effect, likely moderated by other physiological functions. Estradiol is significantly reduced in post-reproductive females, but was not increased in post-reproductive females that received new ovaries, suggesting an estradiol-independent, but ovarian-dependent influence on immune function. Further evidence for an estradiol-independent influence includes the restoration of immune function through the transplantation of young ovaries depleted of follicles and through the injection of isolated ovarian somatic cells into the senescent ovaries of old mice. While the restoration of naïve T-cell populations represents only a small part of the immune system, the ability to reverse this important functional parameter independent of estradiol may hold promise for the improvement of post-reproductive female immune health. Further studies of the non-reproductive influence of the ovary will be needed to elucidate the mechanisms of the relationship between the ovary and health.
Topics: Female; Mice; Animals; Estradiol; T-Lymphocytes; Ovary; Reproduction; Aging
PubMed: 36755910
DOI: 10.3389/fendo.2023.1066356 -
BioEssays : News and Reviews in... Nov 2019Given an equal sex ratio at conception, the excess of human males at birth can only be explained by greater loss of females during pregnancy. It is proposed that the... (Review)
Review
Given an equal sex ratio at conception, the excess of human males at birth can only be explained by greater loss of females during pregnancy. It is proposed that the bias against females during human development is the result of a greater degree of genetic and metabolic "differentness" between female embryos and maternal tissues than for similarly aged males, and that successful implantation and placentation represents a threshold dichotomy, where the acceptance threshold shifts depending on maternal condition, especially stress. Right and left ovaries are not equal, and neither are the eggs and follicular fluid that they produce, and it is further hypothesized that during times of stress, the implantation threshold is shifted sufficiently to favor survival of females, most likely those originating from the right ovary, and that this, rather than simply a greater loss of males, explains at least some of the variability in the human sex ratio at birth.
Topics: Animals; Embryo Implantation; Embryo, Mammalian; Female; Humans; Ovary; Placentation; Pregnancy
PubMed: 31577042
DOI: 10.1002/bies.201900063 -
Zoology (Jena, Germany) Oct 2023Ovaries in earthworms belonging to the family Megascolecidae are paired structures attached to the septum in the anterior part of the XIII segment. They are fan to...
Ovaries in earthworms belonging to the family Megascolecidae are paired structures attached to the septum in the anterior part of the XIII segment. They are fan to rosette shaped with numerous rows of growing oocytes, known as egg strings, radiating from the ovary center towards the segmental cavity. The histological and ultrastructural ovary organization in megascolecids and the course of oogenesis remain unknown. The paper presents the results of light and electron microscopy analyses of ovaries in six megascolecid species, three from the genus Amynthas and three from Metaphire. Both parthenogenetic and sexually reproducing species were included in the study. The organization and ultrastructure of ovaries in all studied species are broadly similar. Considering the histological organization of ovaries, they could be divided into two zones. Zone I (proximal, close to the connection with the septum) is tightly packed with germline and somatic cells. Germ cells are interconnected via intercellular bridges and thin strands of the central cytoplasm (known as cytophore) and form syncytial cysts. Cysts unite oogonia, early meiotic cells (till diplotene), and clustering cells develop synchronously. During diplotene, interconnected cells lose developmental synchrony; most probably, one cell per cyst grows faster than others, detaches from the cysts, and becomes an oocyte. The remaining cells grow slightly and are still interconnected via the thin and reticular cytophore; these cells are considered nurse cells. Zone II has a form of egg strings where growing oocytes are isolated one from another by thin somatic cells and form short cords. We present the ultrastructural details of germline and somatic cells. We propose the term "Amynthas" type of ovaries for this ovary organization. We suppose that such ovaries are characteristic of other megascolecids and related families.
Topics: Humans; Female; Animals; Ovary; Oligochaeta; Oocytes; Oogenesis; Germ Cells
PubMed: 37586295
DOI: 10.1016/j.zool.2023.126109 -
The Journal of Reproduction and... Aug 2019Eggs are female germ cells that are required for producing offspring through sexual reproduction. In mammals, eggs are produced in the ovary and ovulated into the... (Review)
Review
Eggs are female germ cells that are required for producing offspring through sexual reproduction. In mammals, eggs are produced in the ovary and ovulated into the oviduct. It is well known that over 99% of eggs are degenerated without ovulation, so that many studies have attempted in vitro folliculogenesis to produce many eggs in different species for a few decades. Although many methods have been developed, a success of in vitro egg production with the resultant live birth of offspring has been limited, especially in livestock animals. More recently, we have succeeded in producing live pups derived from in vitro/ex vivo egg production in mice. This review aims to introduce our recent findings with a brief history of in vitro/ex vivo culture systems for follicles and ovaries.
Topics: Animals; Cells, Cultured; Female; Humans; In Vitro Oocyte Maturation Techniques; Mammals; Mice; Oocytes; Oogenesis; Ovarian Follicle; Ovary; Ovulation
PubMed: 31006727
DOI: 10.1262/jrd.2019-024 -
Advances in Experimental Medicine and... 2020Malignancy may unfortunately present quite early in a woman's life. In the case of breast cancer, rescue of the breast cancer patient's life is the top priority, but... (Review)
Review
Malignancy may unfortunately present quite early in a woman's life. In the case of breast cancer, rescue of the breast cancer patient's life is the top priority, but after completion of the effective treatment , the question about the ability to accomplish a pregnancy arises. The treatment strategies in breast cancer patients include surgical interventions, chemotherapy , radiotherapy, hormonal therapy and other special types of mainly targeted biologic therapies. Under normal circumstances, surgery for breast cancer does not involve any intervention in the ovaries or the uterus. Thus, even after an extended operation, the anatomic integrity of the gynecological system is guaranteed, and fertility is unaffected.The chemotherapeutic factors that influence fertility are the drug category used, the total dose given, the patient's age at treatment , the drug combination and finally whether targeted therapy is used or not. Alkylating agents are considered to be the most toxic ones. In young breast cancer patients there is a trend to modify regimens to achieve less gonadotoxicity.Evidence regarding tamoxifen, the main used endocrine drug, is scarce and controversial on its direct effect on ovarian reserve. There are not enough studies on the impact of aromatase inhibitors on fertility. Also, HER2-directed agents have not yet demonstrated significant ovarian toxicity and there are scarce data on their effect on fertility.
Topics: Aromatase Inhibitors; Breast Neoplasms; Female; Fertility; Fertility Preservation; Humans; Infertility, Female; Ovarian Reserve; Ovary; Pregnancy; Tamoxifen
PubMed: 32816279
DOI: 10.1007/978-3-030-41596-9_24 -
Journal of Assisted Reproduction and... Jan 2021To study the effect of aging on ovarian circadian rhythm.
OBJECTIVE
To study the effect of aging on ovarian circadian rhythm.
DESIGN
Human and animal study.
SETTING
University hospital and research laboratory.
PATIENTS/ANIMALS
Human granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.
RESULT(S)
All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.
CONCLUSION(S)
Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.
Topics: Aging; Animals; Anti-Mullerian Hormone; Circadian Rhythm; Female; Fertilization in Vitro; Granulosa Cells; Humans; Liver; Mice; Ovarian Reserve; Ovary; RNA, Messenger
PubMed: 32926298
DOI: 10.1007/s10815-020-01943-y -
Stem Cell Research & Therapy Apr 2024Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex...
BACKGROUND
Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem.
METHODS
In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay.
RESULTS
Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary.
CONCLUSIONS
The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn't proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.
Topics: Female; Animals; Mesenchymal Stem Cells; Mice; Ovary; Oocytes; Mesenchymal Stem Cell Transplantation; Ovarian Follicle
PubMed: 38650029
DOI: 10.1186/s13287-024-03718-z