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International Journal of Molecular... Apr 2024The decline in female fecundity is linked to advancing chronological age. The ovarian reserve diminishes in quantity and quality as women age, impacting reproductive... (Review)
Review
The decline in female fecundity is linked to advancing chronological age. The ovarian reserve diminishes in quantity and quality as women age, impacting reproductive efficiency and the aging process in the rest of the body. NAD is an essential coenzyme in cellular energy production, metabolism, cell signaling, and survival. It is involved in aging and is linked to various age-related conditions. Hallmarks associated with aging, diseases, and metabolic dysfunctions can significantly affect fertility by disturbing the delicate relationship between energy metabolism and female reproduction. Enzymes such as sirtuins, PARPs, and CD38 play essential roles in NAD biology, which actively consume NAD in their enzymatic activities. In recent years, NAD has gained much attention for its role in aging and age-related diseases like cancer, Alzheimer's, cardiovascular diseases, and neurodegenerative disorders, highlighting its involvement in various pathophysiological processes. However, its impact on female reproduction is not well understood. This review aims to bridge this knowledge gap by comprehensively exploring the complex interplay between NAD biology and female reproductive aging and providing valuable information that could help develop plans to improve women's reproductive health and prevent fertility issues.
Topics: Humans; Female; NAD; Aging; Ovary; Animals; Sirtuins; Energy Metabolism; Fertility; Reproduction
PubMed: 38731898
DOI: 10.3390/ijms25094680 -
International Journal of Molecular... Sep 2023Maturation is a critical step in the development of an oocyte, and it is during this time that the oocyte advances to metaphase II (MII) of the meiotic cycle and...
Maturation is a critical step in the development of an oocyte, and it is during this time that the oocyte advances to metaphase II (MII) of the meiotic cycle and acquires developmental competence to be fertilized and become an embryo. However, in vitro maturation (IVM) remains one of the limiting steps in the in vitro production of embryos (IVP), with a variable percentage of oocytes reaching the MII stage and unpredictable levels of developmental competence. Understanding the dynamics of oocyte maturation is essential for the optimization of IVM culture conditions and subsequent IVP outcomes. Thus, the aim of this study was to elucidate the transcriptome dynamics of oocyte maturation by comparing transcriptomic changes during in vitro maturation in both oocytes and their surrounding cumulus cells. Cumulus-oocyte complexes were obtained from antral follicles and divided into two groups: immature and in vitro-matured (MII). RNA was extracted separately from oocytes (OC) and cumulus cells (CC), followed by library preparation and RNA sequencing. A total of 13,918 gene transcripts were identified in OC, with 538 differentially expressed genes (DEG) between immature OC and in vitro-matured OC. In CC, 13,104 genes were expressed with 871 DEG. Gene ontology (GO) analysis showed an association between the DEGs and pathways relating to nuclear maturation in OC and GTPase activity, extracellular matrix organization, and collagen trimers in CC. Additionally, the follicle-stimulating hormone receptor gene () and luteinizing hormone/choriogonadotropin receptor gene () showed differential expressions between CC-MII and immature CC samples. Overall, these results serve as a foundation to further investigate the biological pathways relevant to oocyte maturation in horses and pave the road to improve the IVP outcomes and the overall clinical management of equine assisted reproductive technologies (ART).
Topics: Animals; Horses; Female; Transcriptome; Oocytes; Ovarian Follicle; Gene Expression Profiling; Cumulus Cells
PubMed: 37762020
DOI: 10.3390/ijms241813718 -
Molecular Human Reproduction Jul 2023The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of... (Review)
Review
The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of extensive research for decades, characterization of non-canonical progesterone receptor/signaling pathways provided a new perspective for understanding the complex signal transduction mechanisms exploited by the progesterone hormone. Deciphering these mechanisms has significant implications in the management of luteal phase disorders and early pregnancy complications. The purpose of this review is to highlight the complex mechanisms through which progesterone-induced signaling mediates luteal granulosa cell activity in the corpus luteum. Here, we review the literature and discuss the up-to-date evidence on how paracrine and autocrine effects of progesterone regulate luteal steroidogenic activity. We also review the limitations of the published data and highlight future research priorities.
Topics: Female; Humans; Pregnancy; Corpus Luteum; Granulosa Cells; Hormones; Progesterone; Signal Transduction
PubMed: 37289566
DOI: 10.1093/molehr/gaad022 -
Journal of Advanced Research Apr 2024Ovarian steroidogenesis not only affects the embryonic development and pregnancy outcome, but also associates with many diseases in mammals and women. Exploring the...
INTRODUCTION
Ovarian steroidogenesis not only affects the embryonic development and pregnancy outcome, but also associates with many diseases in mammals and women. Exploring the nutrients and mechanisms influencing ovarian steroidogenesis is critical to maintaining the optimal reproductive performance, as well as guaranteeing body health.
OBJECTIVES
This research aimed to explore the effect of retinol metabolism on ovarian steroidogenesis and the underlying mechanisms.
METHODS
Comparative transcriptomic analysis of ovaries from normal and low reproductive performance sows were performed to identify the main causes leading to low fertility. The metabolites regulating steroid hormones synthesis were investigated in ovarian granulosa cells. Gene interference, overexpression, dual-luciferase reporter assays, chromatin immunoprecipitation and transcriptome analysis were further conducted to explore the underlying mechanisms of Aldh1a1 mediating ovarian steroidogenesis.
RESULTS
Transcriptome analysis of ovaries from normal and low reproductive performance sows showed the significant differences in both retinol metabolism and steroid hormones synthesis, indicating retinol metabolism probably influenced steroid hormones synthesis. The related metabolite retinoic acid was furtherly proven a highly active and potent substance strengthening estrogen and progesterone synthesis in ovarian granulosa cells. For the first time, we revealed that retinoic acid synthesis in porcine and human ovarian granulosa cells was dominated by Aldh1a1, and required the assistance of Aldh1a2. Importantly, we demonstrated that Aldh1a1 enhanced the proliferation of ovarian granulosa cells by activating PI3K-Akt-hedgehog signaling pathways. In addition, Aldh1a1 regulated the expression of transcription factor MESP2, which targeted the transcription of Star and Cyp11a1 through binding to corresponding promoter regions.
CONCLUSION
Our data identified Aldh1a1 modulates ovarian steroidogenesis through enhancing granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway. These findings provide valuable clues for improving ovarian health in mammals.
Topics: Female; Swine; Animals; Pregnancy; Humans; Ovary; Cholesterol Side-Chain Cleavage Enzyme; Tretinoin; Phosphatidylinositol 3-Kinases; Vitamin A; Hedgehog Proteins; Progesterone; Cell Proliferation; Mammals; Basic Helix-Loop-Helix Transcription Factors
PubMed: 37315842
DOI: 10.1016/j.jare.2023.06.002 -
Reproductive Biology and Endocrinology... Oct 2023With advanced maternal age, abnormalities during oocyte meiosis increase significantly. Aneuploidy is an important reason for the reduction in the quality of aged...
BACKGROUND
With advanced maternal age, abnormalities during oocyte meiosis increase significantly. Aneuploidy is an important reason for the reduction in the quality of aged oocytes. However, the molecular mechanism of aneuploidy in aged oocytes is far from understood. Histone acetyltransferase 1 (HAT1) has been reported to be essential for mammalian development and genome stability, and involved in multiple organ aging. Whether HAT1 is involved in ovarian aging and the detailed mechanisms remain to be elucidated.
METHODS
The level of HAT1 in aged mice ovaries was detected by immunohistochemical and immunoblotting. To explore the function of HAT1 in the process of mouse oocyte maturation, we used Anacardic Acid (AA) and small interfering RNAs (siRNA) to culture cumulus-oocyte complexes (COCs) from ICR female mice in vitro and gathered statistics of germinal vesicle breakdown (GVBD), the first polar body extrusion (PBE), meiotic defects, aneuploidy, 2-cell embryos formation, and blastocyst formation rate. Moreover, the human granulosa cell (GC)-like line KGN cells were used to investigate the mechanisms of HAT1 in this progress.
RESULTS
HAT1 was highly expressed in ovarian granulosa cells (GCs) from young mice and the expression of HAT1 was significantly decreased in aged GCs. AA and siRNAs mediated inhibition of HAT1 in GCs decreased the PBE rate, and increased meiotic defects and aneuploidy in oocytes. Further studies showed that HAT1 could acetylate Forkhead box transcription factor O1 (FoxO1), leading to the translocation of FoxO1 into the nucleus. Resultantly, the translocation of acetylated FoxO1 increased the expression of amphiregulin (AREG) in GCs, which plays a significant role in oocyte meiosis.
CONCLUSION
The present study suggests that decreased expression of HAT1 in GCs is a potential reason corresponding to oocyte age-related meiotic defects and provides a potential therapeutic target for clinical intervention to reduce aneuploid oocytes.
Topics: Animals; Female; Humans; Mice; Aneuploidy; Granulosa Cells; Histone Acetyltransferases; Mammals; Meiosis; Mice, Inbred ICR; Oocytes
PubMed: 37907924
DOI: 10.1186/s12958-023-01147-w -
Journal of Ovarian Research Jun 2024Thyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence... (Review)
Review
Thyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence and reproductive age, can lead to lifelong ovarian dysfunction. Autoimmune thyroid disease (AITD), one of the most common organ specific autoimmune diseases, is mainly mediated by cellular autoimmune reactions, and has strong inflammatory infiltration and immune active cells, including chemokines and cytokines, which are important components of ovarian aging. This suggests that autoimmune and inflammatory molecular processes may play a role in the emergence of ovarian dysfunction. The purpose of this review is to summarize recent in vivo and in vitro evidence of a complex relationship between AITD and ovarian dysfunction. AITD is closely related to the decline of ovarian function from the perspective of antibody, cytokine, oxidative stress, and genetic factors. Finally, some of the currently known treatments for AITD and hypo ovarian disease are summarized.
Topics: Humans; Female; Autoimmune Diseases; Ovarian Diseases; Thyroid Diseases; Ovary; Animals
PubMed: 38877588
DOI: 10.1186/s13048-024-01451-y -
Animal Reproduction Science Aug 2023The environment encountered by the fetus during its development exerts a profound influence on its physiological function and disease risk in adulthood. Women's intake... (Review)
Review
The environment encountered by the fetus during its development exerts a profound influence on its physiological function and disease risk in adulthood. Women's intake of high-fat diet during pregnancy and lactation has gradually become an issue of widespread concern. Maternal high-fat diet will not only cause abnormal neurological development and metabolic syndrome symptoms in the offspring, but also affect the fertility of female offspring. Maternal high-fat diet affects the expression of genes related to follicle growth in offspring, such as AAT, AFP and GDF-9, which reduces the number of follicles and impairs follicle development. Additionally, maternal high-fat diet also affects ovarian health by inducing ovarian oxidative stress and cell apoptosis, which collectively can impair the reproductive potential of female offspring. Reproductive potential carries significant importance for both humans and animals. Therefore, this review aims to describe the effect of maternal exposure to high-fat diet on the ovarian development of offspring and to discuss possible mechanisms by which maternal diet affects the growth and metabolism of offspring.
Topics: Pregnancy; Female; Animals; Humans; Diet, High-Fat; Prenatal Exposure Delayed Effects; Reproduction; Ovary; Ovarian Follicle; Lactation; Maternal Nutritional Physiological Phenomena
PubMed: 37421833
DOI: 10.1016/j.anireprosci.2023.107294 -
Biological Trace Element Research Nov 2023Infertility has become more common, with an increased exposure to toxic compounds including heavy metals (HM). Follicular fluid (FF) surrounds the developing oocyte in...
Infertility has become more common, with an increased exposure to toxic compounds including heavy metals (HM). Follicular fluid (FF) surrounds the developing oocyte in the ovary and can be analysed to assess metal content. The levels of twenty-two metals were measured in the FF of ninety-three females in a reproduction unit, and their influence on assisted reproduction technique (ART), were examined. The metals were determined by optical emission spectrophotometry. Low values of copper, zinc, aluminium, and calcium favour polycystic ovary syndrome. The relationships between the number of oocytes and metals: iron (r=0.303; p=0.003) and calcium (r=-0.276; p=0.007) are significant, as well as between the number of mature oocytes with iron (r=0.319; p=0.002), calcium (r=-0.307; p=0.003) and sodium (r=-0.215; p=0.039) and are near to significance in the case of aluminium (r=-0.198; p=0.057). In the group with a fertilisation rate ≤ 75%, 36% of the women presented calcium >176.62 mg/kg compared to the group with a fertilisation rate ≥ 75% where this percentage was only 10% (p=0.011). An excess of iron and calcium reduces the good quality embryo rate, and an excess of potassium impairs the blastocyst rate. If potassium is above 237.18 mg/kg and calcium is below 147.32 mg/kg, these conditions favour embryo implantation. Pregnancy is influenced by high potassium and low copper levels. Controlling exposure to toxic elements is recommended for all couples with reduced fertility or receiving an ART.
Topics: Pregnancy; Humans; Female; Follicular Fluid; Copper; Calcium; Aluminum; Reproduction; Iron; Potassium
PubMed: 36807885
DOI: 10.1007/s12011-023-03578-3 -
Cell Proliferation May 2024Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To...
Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To address this problem, it is necessary to induce functional granulosa cells at different stages in vitro. In this study, we established a reprogramming method to induce early- and late-stage granulosa cells with different steroidogenic abilities. We used an AMH-fluorescence-reporter system to screen candidate factors for cellular reprogramming and generated human induced granulosa-like cells (hiGC) by overexpressing FOXL2 and NR5A1. AMH-EGFP hiGC resembled human cumulus cells in transcriptome profiling and secreted high levels of oestrogen and progesterone, similar to late-stage granulosa cells at antral or preovulatory stage. Moreover, we identified CD55 as a cell surface marker that can be used to isolate early-stage granulosa cells. CD55 AMH-EGFP hiGC secreted high levels of oestrogen but low levels of progesterone, and their transcriptome profiles were more similar to early-stage granulosa cells. More importantly, CD55 hiGC transplantation alleviated polycystic ovary syndrome (PCOS) in a mouse model. Therefore, hiGC provides a cellular model to study the developmental program of human granulosa cells and has potential to treat PCOS.
Topics: Female; Humans; Forkhead Box Protein L2; Granulosa Cells; Animals; Mice; Fibroblasts; Steroidogenic Factor 1; Progesterone; Polycystic Ovary Syndrome; Cellular Reprogramming; Cells, Cultured
PubMed: 38192172
DOI: 10.1111/cpr.13589 -
Current Oncology (Toronto, Ont.) Jan 2024Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly... (Review)
Review
Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger tumors (2-4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative option. Several chemotherapy regimens have been used for this indication, with a pathologic complete response rate of 17-73%. For locally advanced diseases that require radical hysterectomy or primary chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming more acceptable. Additional and ongoing evidence is helping determine the impact of conservative procedures on oncologic and obstetric outcomes in these patients.
Topics: Pregnancy; Humans; Female; Fertility Preservation; Uterine Cervical Neoplasms; Neoadjuvant Therapy; Cryopreservation; Ovary
PubMed: 38248104
DOI: 10.3390/curroncol31010019