-
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 -
Climacteric : the Journal of the... Aug 2023Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological... (Review)
Review
Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.
Topics: Humans; Female; Quality of Life; Estrogens; Vaginal Diseases; Dyspareunia; Hormone Replacement Therapy; Vagina; Atrophy; Menopause
PubMed: 37318030
DOI: 10.1080/13697137.2023.2218998 -
Cold Spring Harbor Protocols Jul 2023Upon copulation, females undergo a switch-like change in their behavior and physiology, known as "postmating responses." These strong behavioral and physiological...
Upon copulation, females undergo a switch-like change in their behavior and physiology, known as "postmating responses." These strong behavioral and physiological changes are triggered by the transfer of male seminal proteins during copulation. Postmating response is associated with strong reduction in receptivity, indicated by the females kicking their legs toward the suitor and curving their abdomen downward to hide their genitalia from them and extruding their ovipositor at the tip of the abdomen, which physically prevents copulation. The transfer of male-specific pheromones, such as 11--vaccenyl-acetate, during copulation further reduces female attractiveness. In addition, mated females exhibit increased ovulation, egg-laying behavior, enhanced feeding behavior, and changes in food preference. However, females increase their rate of remating when they are in social groups or in the presence of food. This protocol describes methods for measuring female postmating behaviors, such as oviposition, female sexual receptivity, and mating plug ejection.
Topics: Animals; Female; Male; Sexual Behavior, Animal; Copulation; Ovulation
PubMed: 36781215
DOI: 10.1101/pdb.prot108108 -
Plants (Basel, Switzerland) Aug 2023Embryo rescue (ER) techniques are among the oldest and most successful in vitro tissue culture protocols used with plant species. ER refers to a series of methods that... (Review)
Review
Embryo rescue (ER) techniques are among the oldest and most successful in vitro tissue culture protocols used with plant species. ER refers to a series of methods that promote the development of an immature or lethal embryo into a viable plant. Intraspecific, interspecific, or intergeneric crosses allow the introgression of important alleles of agricultural interest from wild species, such as resistance or tolerance to abiotic and biotic stresses or morphological traits in crops. However, pre-zygotic and post-zygotic reproductive barriers often present challenges in achieving successful hybridization. Pre-zygotic barriers manifest as incompatibility reactions that hinder pollen germination, pollen tube growth, or penetration into the ovule occurring in various tissues, such as the stigma, style, or ovary. To overcome these barriers, several strategies are employed, including cut-style or graft-on-style techniques, the utilization of mixed pollen from distinct species, placenta pollination, and in vitro ovule pollination. On the other hand, post-zygotic barriers act at different tissues and stages ranging from early embryo development to the subsequent growth and reproduction of the offspring. Many crosses among different genera result in embryo abortion due to the failure of endosperm development. In such cases, ER techniques are needed to rescue these hybrids. ER holds great promise for not only facilitating successful crosses but also for obtaining haploids, doubled haploids, and manipulating the ploidy levels for chromosome engineering by monosomic and disomic addition as well substitution lines. Furthermore, ER can be used to shorten the reproductive cycle and for the propagation of rare plants. Additionally, it has been repeatedly used to study the stages of embryonic development, especially in embryo-lethal mutants. The most widely used ER procedure is the culture of immature embryos taken and placed directly on culture media. In certain cases, the in vitro culture of ovule, ovaries or placentas enables the successful development of young embryos from the zygote stage to maturity.
PubMed: 37687352
DOI: 10.3390/plants12173106 -
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 -
IScience Aug 2023Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS...
Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS protocol was simulated in mice. The ovulated oocytes, estradiol, progesterone, and luteinizing hormone (LH) levels were analyzed at different hours after trigger. mRNA extraction and real-time PCR, hematoxylin and eosin staining, and immunofluorescence of ovaries were used to explore the involved signaling pathways. The PPOS group had a delayed ovulation at 12.5 h after trigger. Its suppressed LH level reduced the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) on the preovulatory follicles before trigger and significantly decreased the following progesterone synthesis, blood progesterone level, and progesterone receptor (PGR) expression within 4-6 h after trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS-1, VEGF-A, and EDN2 were downregulated, ultimately delaying the ovulation. PPOS suppresses the LH level before trigger and decreases the synthesis of progesterone after trigger, thus delaying the ovulation by downregulating the LHCGR-PGR pathway.
PubMed: 37520702
DOI: 10.1016/j.isci.2023.107357 -
Clinics (Sao Paulo, Brazil) 2023PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would... (Review)
Review
PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation; Phenols
PubMed: 38008036
DOI: 10.1016/j.clinsp.2023.100310 -
Journal of Experimental Zoology. Part... Dec 2023Female reproductive success is one of the most important life-history traits to be monitored when determining population dynamics in free-ranging ungulates. Several...
Female reproductive success is one of the most important life-history traits to be monitored when determining population dynamics in free-ranging ungulates. Several studies have described how phenotypic characteristics of the mother, climatic conditions, population status, and habitat can impact on potential reproductive output in wild ungulates. However, little is known regarding the internal, physiological factors, that may account for differences in implantation rates. The present study investigated the differences in implantation rates and site on the basis of site and number of ovulations through the examination of about 3000 intact uteri collected from pregnant roe deer does (Capreolus capreolus). Although ovulation occurs with the same frequency in the left and right ovary, we revealed a higher frequency of embryos implantation in the left uterine horn in odd litter size, demonstrating that embryos can migrate between the uterine horns. In our study, a greater proportion of reproductive wastage was associated to females with three and four corpora lutea and interestingly, in relation to the site of ovulation, the percentage of corpora lutea that did not correspond to a fetus was higher in the right ovary than in the left one (73.2% vs. 26.8%). Our research described for the first time the absence of laterality in ovulation and the presence of laterality in implantation in roe deer, thus laying the foundations for in-depth studies about the functionality of this uterine side and for comparisons with populations located in other geographical areas to understand whether it is a widespread phenomenon or a local adaptation.
Topics: Pregnancy; Animals; Female; Deer; Corpus Luteum; Ovary; Ecosystem; Reproduction
PubMed: 37602642
DOI: 10.1002/jez.2748 -
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