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Frontiers in Immunology 2023Ovulation dysfunction is now a widespread cause of infertility around the world. Although the impact of immune cells in human reproduction has been widely investigated,...
INTRODUCTION
Ovulation dysfunction is now a widespread cause of infertility around the world. Although the impact of immune cells in human reproduction has been widely investigated, systematic understanding of the changes of the immune atlas under female ovulation remain less understood.
METHODS
Here, we generated single cell transcriptomic profiles of 80,689 PBMCs in three representative statuses of ovulation dysfunction, i.e., polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and menopause (MENO), and identified totally 7 major cell types and 25 subsets of cells.
RESULTS
Our study revealed distinct cluster distributions of immune cells among individuals of ovulation disorders and health. In patients with ovulation dysfunction, we observed a significant reduction in populations of naïve CD8 T cells and effector memory CD4 T cells, whereas circulating NK cells and regulatory NK cells increased.
DISCUSSION
Our results highlight the significant contribution of cDC-mediated signaling pathways to the overall inflammatory response within ovulation disorders. Furthermore, our data demonstrated a significant upregulation of oxidative stress in patients with ovulation disorder. Overall, our study gave a deeper insight into the mechanism of PCOS, POI, and menopause, which may contribute to the better diagnosis and treatments of these ovulatory disorder.
Topics: Female; Humans; Polycystic Ovary Syndrome; Transcriptome; Ovulation; Infertility, Female
PubMed: 38116006
DOI: 10.3389/fimmu.2023.1297484 -
Proceedings of the National Academy of... Jan 2024Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal...
Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal transcriptomics to map out cell type- and ovulation stage-specific molecular programs as function of time during follicle maturation and ovulation in mice. Our analysis revealed dynamic molecular transitions within granulosa cell types that occur in tight coordination with mesenchymal cell proliferation. We identified molecular markers for the emerging cumulus cell fate during the preantral-to-antral transition. We describe transcriptional programs that respond rapidly to ovulation stimulation and those associated with follicle rupture, highlighting the prominent roles of apoptotic and metabolic pathways during the final stages of follicle maturation. We further report stage-specific oocyte-cumulus cell interactions and diverging molecular differentiation in follicles approaching ovulation. Collectively, this study provides insights into the cellular and molecular processes that regulate mouse ovarian follicle maturation and ovulation with important implications for advancing therapeutic strategies in reproductive medicine.
Topics: Female; Animals; Mice; Ovary; Ovulation; Ovarian Follicle; Reproduction; Granulosa Cells; Ascomycota
PubMed: 38252830
DOI: 10.1073/pnas.2317418121 -
International Journal of Molecular... Sep 2019Methylation of cytosine (5-meC) is a critical epigenetic modification in many eukaryotes, and genomic DNA methylation landscapes are dynamically regulated by opposed... (Review)
Review
Methylation of cytosine (5-meC) is a critical epigenetic modification in many eukaryotes, and genomic DNA methylation landscapes are dynamically regulated by opposed methylation and demethylation processes. Plants are unique in possessing a mechanism for active DNA demethylation involving DNA glycosylases that excise 5-meC and initiate its replacement with unmodified C through a base excision repair (BER) pathway. Plant BER-mediated DNA demethylation is a complex process involving numerous proteins, as well as additional regulatory factors that avoid accumulation of potentially harmful intermediates and coordinate demethylation and methylation to maintain balanced yet flexible DNA methylation patterns. Active DNA demethylation counteracts excessive methylation at transposable elements (TEs), mainly in euchromatic regions, and one of its major functions is to avoid methylation spreading to nearby genes. It is also involved in transcriptional activation of TEs and TE-derived sequences in companion cells of male and female gametophytes, which reinforces transposon silencing in gametes and also contributes to gene imprinting in the endosperm. Plant 5-meC DNA glycosylases are additionally involved in many other physiological processes, including seed development and germination, fruit ripening, and plant responses to a variety of biotic and abiotic environmental stimuli.
Topics: 5-Methylcytosine; DNA Demethylation; DNA Glycosylases; DNA Methylation; DNA, Plant; Endosperm; Gene Expression Regulation, Plant; Genomic Instability; Ovule; Plants; Pollen; Stress, Physiological
PubMed: 31546611
DOI: 10.3390/ijms20194683 -
Cell Reports Jun 2023Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation,...
Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca] transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals.
Topics: Mice; Animals; Female; Gonadotrophs; Pituitary Gland, Anterior; Luteinizing Hormone; Pituitary Gland; Ovulation; Mammals
PubMed: 37224016
DOI: 10.1016/j.celrep.2023.112543 -
Journal of Medicine and Life Jan 2024Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to compare the effects of green tea tablets and metformin on ovulation, menstrual cycle regularity, and antioxidant biomarkers in women with polycystic ovary syndrome (PCOS). In this clinical trial study, 94 women with PCOS were randomly assigned to three groups: green tea ( = 33), metformin ( = 29), and control ( = 32). Menstrual status and oxidative stress parameters, including total antioxidant capacity, thiol, and lipid peroxidation, were compared before and 3 months after the intervention among all three groups. Data analysis was conducted using SPSS software version 22 and employing the analysis of variance and paired t-tests. Following the intervention, the mean menstrual cycle duration in the green tea, metformin, and control groups was 32.22 ± 12.78, 48.72 ± 37.06, and 48.53 ± 31.04 days, respectively ( = 0.040). There was no statistically significant difference between the three groups in terms of biochemical, hormonal, and antioxidant indices before and after the intervention ( > 0.05). The intake of green tea tablets was associated with better outcomes in regulating the menstrual cycle in women with PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Metformin; Tea; Menstrual Cycle; Adult; Ovulation; Tablets; Young Adult; Antioxidants; Oxidative Stress
PubMed: 38737668
DOI: 10.25122/jml-2022-0066 -
Theriogenology Sep 2021Although prostaglandins are important in the ovulation process, a precise role for prostaglandin F2α (PGF) has not been elucidated. This study aimed to evaluate the...
Although prostaglandins are important in the ovulation process, a precise role for prostaglandin F2α (PGF) has not been elucidated. This study aimed to evaluate the regulation of PGF receptor mRNA (PTGFR) in granulosa cells and the local effect of PGF on ovulation and luteinization. In Experiment 1, using samples collected in vivo before (Day 2), during (Day 3) and after (Day 4) follicular deviation, expression of PTGFR in bovine granulosa cells was more abundant in the dominant follicle after deviation than in subordinates (P < 0.05). However, the expression of PTGFR was not regulated (P = 0.1) in preovulatory follicles at different time-points (0, 3, 6, 12 and 24 h) after ovulation induction with GnRH. In Experiment 2, to assess the role of systemic PGF treatment on luteinization and vascularization of preovulatory follicles, flunixin meglumine (FM), a nonsteroidal anti-inflammatory drug, was used to inhibit endogenous prostaglandin synthesis. Cows with preovulatory follicles were induced to ovulate with GnRH (0 h) and allocated to three groups: Control, with no further treatment; FM, treated with 2.2 mg/kg FM im 17 h after GnRH treatment; and FM + PGF, treated with FM 17 h after GnRH, followed by 25 mg dinoprost tromethamine (PGF) 23 h after GnRH treatment. FM injection was able to reduce the concentration of PGF in the follicular fluid (FF) (P < 0.001). However, contrary to our hypothesis, color Doppler ultrasound evaluations revealed decreased vascular flow in FM + PGF group (P < 0.05), and no effect of the treatments on intrafollicular P4 and E2 concentrations 24 h after GnRH. The prostaglandin metabolite (PGFM) concentrations in the FF were greater in cows receiving systemic PGF (P < 0.001), which prompted us to further check its role on ovulation. Therefore, in Experiment 3, in a final attempt to demonstrate the local effect of PGF on ovulation, cows with preovulatory follicles received an intrafollicular injection (IFI) of PBS (Control) or 100 ng/mL purified PGF (PGF group). PGF treatment did not affect the time of ovulation after IFI (66 ± 6.4 and 63 ± 8.5 h for control and PGF, respectively; P > 0.05), further suggesting that it has no direct effect in the ovulatory process. Based on our findings, we concluded that FM decreased PGF synthesis within the follicle, whereas PGF treatment decreased follicular vascularization. In addition, the in vivo model of intrafollicular injection evidenced that PGF alone is not able to locally induce ovulation.
Topics: Animals; Cattle; Dinoprost; Female; Gonadotropin-Releasing Hormone; Luteinization; Ovarian Follicle; Ovulation; Progesterone
PubMed: 34004368
DOI: 10.1016/j.theriogenology.2021.05.008 -
American Journal of Primatology Jun 2021In nearly four decades our research and that of others on chemical signaling in callitrichid primates suggest a high degree of contextual complexity in both the use of... (Review)
Review
In nearly four decades our research and that of others on chemical signaling in callitrichid primates suggest a high degree of contextual complexity in both the use of signals and the response to these signals. We describe our research including observational field studies, behavioral bioassays ("playbacks"), functional imaging, and conditioning studies. Scent marking in both captivity and the wild is used for more than just territorial marking. Social contextual effects are seen in responses by subordinate females responding with ovulatory inhibition only to chemical signals from familiar dominant reproductive females. Males detect ovulation through changes in scent marks. Males responded behaviorally and hormonally to chemical signals of novel ovulating females as a function of their reproductive status (fathers, males paired with a female but not fathers, and single males). Multiple brain areas are activated in males by female chemical signals of ovulation including areas relating to memory, evaluation, and motivation. Furthermore, males can be conditioned to respond sexually to a nonsexual odor demonstrating that learning plays an important role in response to chemical signals. Male androgen and estrone levels changed significantly in response to infant chemical signals as a function of whether the males were fathers or not, whether the odors were from their own versus other infants, as well as the infant's stage of development. Chemical signals in callitrichids are providing a rich source of understanding the context and function of the chemical sensory system and its stimulation of neural, behavioral, and hormonal actions in the recipients.
Topics: Animals; Female; Male; Odorants; Ovulation; Territoriality
PubMed: 32643223
DOI: 10.1002/ajp.23172 -
Frontiers in Endocrinology 2023To evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome.
METHOD
We searched Pubmed, Medline (via Ovid, 1974 to 2020), EMBASE (via Ovid, 1974 to 2020), Cochrane Central Register of Controlled Trials (via Ovid), Web of Science, CNKI, WangFang and the Vip database from inception until April 2021. Two researchers independently screened articles, collected data and evaluated the quality, with Review manager 5.3 for meta-analysis.
RESULTS
Totally 20 randomized controlled studies with 1961 subjects were included. Meta analysis showed that pregnancy rate [RR=1.44 (1.28, 1.62), p<0.00,001], ovulation rate [RR=1.42 (1.14, 1.78), p=0.002] and matured oocytes rate [RR=1.08 (1.03, 1.13), p=0.002] of vitamin D supplementation group were significantly higher than those of control group. Meanwhile, early miscarriage rate [RR=0.44 (0.30, 0.66), p<0.00,001], androgen level [MD=-2.31 (-3.51, -1.11), p=0.0002], luteinizing hormone [MD=-1.47 (-2.57, -0.36), p=0.009], follicle stimulating hormone [MD=-0.15 (-0.24, -0.05), p=0.002], and premature delivery rate [RR=0.38, 95% CI (0.21, 0.70), p=0.002] were declined significantly than the controls. However, only one article suggested that the progesterone [MD=6.52 (4.52, 8.52), p<0.05] in the vitamin D intervention group was increased. There was no notable difference in the biochemical pregnancy rate [RR=0.95 (0.55, 1.63), p=0.84], gestational hypertension rate [RR=0.40, 95% CI (0.15, 1.11), p=0.08], gestational diabetes mellitus rate [RR=0.27, 95% CI (0.05, 1.39), p=0.11], fertilization rate [RR=1.05 (1.00, 1.10), p=0.04], cleavage rate [RR=1.03 (0.99, 1.06), p=0.17], high-quality embryo rate [RR=1.08 (0.98, 1.20), p=0.10], endometrial thickness [MD=0.10], 77 (-0.23, 1.77), p=0.13], estrogen level [MD=-0.34 (-1.55, 0.87), p=0.59], LH/FSH [MD=-0.14, 95% CI (-0.48, 0.20), p=1.00] and anti-Mullerian hormone [MD=-0.22 (-0.65, 0.21), p=0.32].
CONCLUSION
Vitamin D supplementation contribute to the higher pregnancy and ovulation rates, and lower androgen, LH, FSH and early miscarriage rates in women with PCOS, regardless of the use of ovulation induction drugs or assisted reproductive technologies. However, no significant improvement was observed in fertilization rate or cleavage rate. Due to the limitation in quality of involved studies, more high-quality RCTs are needed for further validation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021250284.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Androgens; Dietary Supplements; Follicle Stimulating Hormone, Human; Ovulation; Polycystic Ovary Syndrome; Vitamin D
PubMed: 37593349
DOI: 10.3389/fendo.2023.1148556 -
Fertility and Sterility Nov 2020Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the...
Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the first woman to be awarded a Tony for Best Direction of a Musical.
Topics: Female; Gynecology; Humans; Luteinizing Hormone; Ovulation; Ovulation Induction
PubMed: 32819679
DOI: 10.1016/j.fertnstert.2020.07.041 -
Frontiers in Endocrinology 2022Every menstrual cycle, many follicles begin to develop but only a specific number ovulate. This ovulation number determines how many offspring are produced per litter,...
Every menstrual cycle, many follicles begin to develop but only a specific number ovulate. This ovulation number determines how many offspring are produced per litter, and differs between species. The physiological mechanism that controls ovulation number is unknown; a class of mathematical models can explain it, but these models have no physiological basis. Here, we suggest a physiological mechanism for ovulation number control, which enables selection of a specific number of follicles out of many, and analyze it in a mathematical model of follicular growth. The mechanism is based on a signal, intra-follicular androgen concentration, that measures follicle size relative to the other follicles. This signal has a biphasic effect, suppressing follicles that are too large or too small compared to others. The ovulation number is determined by the androgen inhibitory thresholds. The model has a scaling symmetry that explains why the dominant follicles grow linearly with time, as observed in human ultrasound data. This approach also explains how chronic hyperandrogenism disrupts ovulation in polycystic ovary syndrome (PCOS), a leading cause of infertility. We propose specific experiments for testing the proposed mechanism.
Topics: Androgens; Female; Humans; Menstrual Cycle; Ovarian Follicle; Ovulation; Polycystic Ovary Syndrome
PubMed: 35909517
DOI: 10.3389/fendo.2022.816967