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Nucleic Acids Research Jul 2023Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key...
Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation.
Topics: Animals; Female; Mice; Chromatin; Chromatin Assembly and Disassembly; Gene Expression Regulation; Mammals; Mice, Knockout; Receptors, Progesterone; Transcription Factors; Core Binding Factor Alpha 2 Subunit; Transcription, Genetic
PubMed: 37099375
DOI: 10.1093/nar/gkad271 -
Sports Medicine - Open Oct 2023Estrogen and progesterone are the primary female sex hormones and have net excitatory and inhibitory effects, respectively, on neuronal function. Fluctuating...
BACKGROUND
Estrogen and progesterone are the primary female sex hormones and have net excitatory and inhibitory effects, respectively, on neuronal function. Fluctuating concentrations across the menstrual cycle has led to several lines of research in relation to neuromuscular function and performance; however evidence from animal and cell culture models has yet to be demonstrated in human motor units coupled with quantification of circulating hormones. Intramuscular electromyography was used to record motor unit potentials and corresponding motor unit potential trains from the vastus lateralis of nine eumenorrheic females during the early follicular, ovulation and mid luteal phases of the menstrual cycle, alongside assessments of neuromuscular performance. Multi-level regression models were applied to explore effects of time and of contraction level. Statistical significance was accepted as p < 0.05.
RESULTS
Knee extensor maximum voluntary contraction, jump power, force steadiness, and balance did not differ across the menstrual phases (all p > 0.4). Firing rate of low threshold motor units (10% maximum voluntary contraction) was lower during the ovulation and mid luteal phases (β = - 0.82 Hz, p < 0.001), with no difference in motor unit potentials analysed from 25% maximum voluntary contraction contractions. Motor unit potentials were more complex during ovulation and mid luteal phase (p < 0.03), with no change in neuromuscular junction transmission instability (p > 0.3).
CONCLUSIONS
Assessments of neuromuscular performance did not differ across the menstrual cycle. The suppression of low threshold motor unit firing rate during periods of increased progesterone may suggest a potential inhibitory effect and an alteration of recruitment strategy; however this had no discernible effect on performance. These findings highlight contraction level-dependent modulation of vastus lateralis motor unit function over the eumenorrheic cycle, occurring independently of measures of performance.
PubMed: 37874413
DOI: 10.1186/s40798-023-00639-8 -
Frontiers in Plant Science 2023The increment in global temperature reduces crop productivity, which in turn threatens food security. Currently, most of our food supply is produced by plants and the... (Review)
Review
The increment in global temperature reduces crop productivity, which in turn threatens food security. Currently, most of our food supply is produced by plants and the human population is estimated to reach 9 billion by 2050. Gaining insights into how plants navigate heat stress in their reproductive phase is essential for effectively overseeing the future of agricultural productivity. The reproductive success of numerous plant species can be jeopardized by just one exceptionally hot day. While the effects of heat stress on seedlings germination and root development have been extensively investigated, studies on reproduction are limited. The intricate processes of gamete development and fertilization unfold within a brief timeframe, largely concealed within the flower. Nonetheless, heat stress is known to have important effects on reproduction. Considering that heat stress typically affects both male and female reproductive structures concurrently, it remains crucial to identify cultivars with thermotolerance. In such cultivars, ovules and pollen can successfully undergo development despite the challenges posed by heat stress, enabling the completion of the fertilization process and resulting in a robust seed yield. Hereby, we review the current understanding of the molecular mechanisms underlying plant resistance to abiotic heat stress, focusing on the reproductive process in the model systems of
PubMed: 38126016
DOI: 10.3389/fpls.2023.1271644 -
Clinical Science (London, England :... Oct 2023The process of ovarian cryopreservation and transplantation is the only feasible fertility preservation method for prepubertal girls and female patients with cancer who...
The process of ovarian cryopreservation and transplantation is the only feasible fertility preservation method for prepubertal girls and female patients with cancer who cannot delay radiotherapy and chemotherapy. However, basic research on this technique is lacking. To better understand ovarian function and oocyte quality after ovarian tissue (OT) transplantation, we characterised the appearance, angiogenesis, and endocrine function of ovarian grafts in a murine model; the mitochondrial function and DNA damage in oocytes isolated from the OT; and the development of embryos after in vitro fertilisation. The results showed a decrease in oocyte numbers in the transplanted OT, abnormal endocrine function of ovarian grafts, as well as dysfunctional mitochondria and DNA damage in the oocytes, which could adversely affect subsequent embryonic development. However, these adverse phenotypes were partially or completely resolved within 21 days of transplantation, suggesting that ovulation induction and assisted pregnancy treatment should not be conducted too soon after OT transfer to ensure optimal patient and offspring outcomes.
Topics: Pregnancy; Humans; Female; Animals; Mice; Disease Models, Animal; Oocytes; Ovary; Cryopreservation; Ovulation Induction
PubMed: 37782233
DOI: 10.1042/CS20230483 -
Botanical Studies Sep 2023Orchid seeds are 'dust-like.' The seed coat is usually thin, with only one to a few cell layers. It originates from the integuments formed during ovule development. In... (Review)
Review
Orchid seeds are 'dust-like.' The seed coat is usually thin, with only one to a few cell layers. It originates from the integuments formed during ovule development. In orchids, the outer integument is primarily responsible for forming a mature seed coat. The inner integument usually fails to develop after fertilization, becomes compressed, and collapses over the expanding embryo. Hence, the seed coat is formed from the funiculus, chalaza, and outer integumentary cells. The outermost layer of the seed coat, the testa, is lignified, usually at the radial and inner tangential walls. The subepidermal thin-walled layer(s), the tegmen, subsequently cold, resulting in seeds having only a single layer of seed coat cells. In some species, cells of the inner integument remain alive with the ability to synthesize and accumulate lipidic and or phenolic compounds in their walls covering the embryo. This cover is called the 'carapace,' a protective shield contributing to the embryo's added protection. A developmental and functional perspective of the integuments and seed coat during seed development and germination is presented in this review.
PubMed: 37755558
DOI: 10.1186/s40529-023-00400-0 -
Frontiers in Endocrinology 2023To evaluate the effectiveness and safety of utilizing the small number of remaining vitrified oocytes after the failure of adequate fresh sibling oocytes. The outcome of... (Review)
Review
Efficiency and safety of vitrification of surplus oocytes following superovulation: a comparison of different clinical indications of oocyte cryopreservation in IVF/ICSI cycles.
OBJECTIVE
To evaluate the effectiveness and safety of utilizing the small number of remaining vitrified oocytes after the failure of adequate fresh sibling oocytes. The outcome of present study would provide more comprehensive information about possible benefits or disadvantage to cryopreserve supernumerary oocytes for patients who have plenty oocytes retrieved.
METHODS
This retrospective cohort study included 791 IVF/ICSI cycles using 6344 oocytes that had been vitrified in the Reproductive Hospital affiliated to Shandong University between January 2013 and December 2019.They were divided into three groups: SOC group (supernumerary oocytes cryopreservation), relative-MOC group (relative male factor-oocyte cryopreservation), and absolute-MOC group (absolute male factor-oocyte cryopreservation). Laboratory and clinical outcomes were analysed, and multivariate regression analysis was used to study the effect of different indications of vitrification on CLBR.
RESULTS
The CLBR was highest in absolute-MOC, and lowest in SOC (39.0% vs 28.9%, P=0.006); however, after adjusting for confounding factors, the difference was not statistically significant. Multivariable regression analysis showed no impact of indications of vitrified oocytes on CLBR according to controlled age, BMI, preservation duration, use of donor sperm or not, use of PESA/TESA or not, number of oocytes retrieved, number of oocytes thawed, and oocyte survival rate. The preliminary data of safety showed no significant differences in the perinatal and neonatal outcoms after ET and FET between the SOC and MOC groups.
CONCLUSION
Different indications of vitrification did not affect CLBR. The CLBR of vitrified oocytes for different indications was correlated with age and number of warmed oocytes. For women who have plenty oocytes retrieved, the strategy of cryopreserving a small number of oocytes is a valuable option and might benefit them in the future. Additional data from autologous oocyte vitrification research employing a large-scale and variable-controlled methodology with extending follow-up will complement and clarify the current results.
Topics: Pregnancy; Infant, Newborn; Male; Humans; Female; Vitrification; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Superovulation; Retrospective Studies; Semen; Cryopreservation; Oocytes
PubMed: 37867517
DOI: 10.3389/fendo.2023.1221308 -
Frontiers in Physiology 2023Ovulation in European eel is induced by injection of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) as the maturation-inducing hormone (MIH). Female eels need to ovulate...
Ovulation in European eel is induced by injection of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) as the maturation-inducing hormone (MIH). Female eels need to ovulate within 18 h after injection to release good quality eggs. Progesterone (P), as an upstream precursor of DHP, may promote endogenous DHP production and improve egg quality. The purpose of this study was therefore to compare treatment of P with DHP on batch level, , to determine dose-response effects, and , at a single dose. For the experiment, ovarian tissue was extracted and placed in culture plates containing hormone-free medium and media supplemented with the treatment: DHP at 1, 10 and 100 ng mL, or P at 10, 100 and 1,000 ng mL. At the start of incubation, the folliculated oocytes were sampled for histology, microscopy and qPCR. After incubation for 12 and 18 h, the oocytes were sampled for microscopy and qPCR analysis. For the experiment, females were either injected with DHP or P at a dose of 2 mg kg to assess their effects on ovulation and reproductive success. At the moment of release, eggs were sampled for RNA sequencing to compare effects of DHP and P on the expression of genes involved in egg quality aspects. Remaining eggs were fertilized and larval viability was recorded. Both DHP and P were able to induce GVBD (DHP at 10 and 100 ng mL, P at 100 and 1,000 ng mL) . Expression of genes involved in oocyte maturation and ovulation was similar for both DHP and P treatments. Regarding the results, RNAseq results reflected similar DHP and P effects on the expression of genes involved in egg quality aspects. Females injected with either DHP or P ovulated, released eggs, and were equally able to produce larvae without any differences in reproductive success. Our results support the conclusion that DHP and P work equally well and . P is more attractive to apply as the price is 3,000 times lower than the price of DHP.
PubMed: 37614755
DOI: 10.3389/fphys.2023.1207542 -
International Journal of Molecular... Jun 2024The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the... (Review)
Review
The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the neuroendocrine background of the regulation of ovulation. We first describe the development of the pituitary gland, the structure of the median eminence (ME), the connection between the hypothalamus and the pituitary gland, the ovarian and pituitary hormones involved in ovulation, and the pituitary cell composition. We recall the pioneer physiological and morphological investigations that drove development forward. The description of the supraoptic-paraventricular magnocellular and tuberoinfundibular parvocellular systems and recognizing the role of the hypophysiotropic area were major milestones in understanding the anatomical and physiological basis of reproduction. The discovery of releasing and inhibiting hormones, the significance of pulse and surge generators, the pulsatile secretion of the gonadotropin-releasing hormone (GnRH), and the subsequent pulsatility of luteinizing (LH) and follicle-stimulating hormones (FSH) in the human reproductive physiology were truly transformative. The roles of three critical neuropeptides, kisspeptin (KP), neurokinin B (NKB), and dynorphin (Dy), were also identified. This review also touches on the endocrine background of human infertility and assisted fertilization.
Topics: Humans; Ovulation; Female; Neurosecretory Systems; Animals; Pituitary Gland; Kisspeptins; Neurokinin B; Luteinizing Hormone; Gonadotropin-Releasing Hormone; Dynorphins; Hypothalamus
PubMed: 38928237
DOI: 10.3390/ijms25126531 -
Frontiers in Cell and Developmental... 2024Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of... (Review)
Review
Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies.
PubMed: 38827527
DOI: 10.3389/fcell.2024.1384047 -
Cureus Jul 2023Background Ovulatory disruption is the primary reversible cause of infertility, which affects 12-24% of couples. The FDA's first-line recommendation for ovulation...
Background Ovulatory disruption is the primary reversible cause of infertility, which affects 12-24% of couples. The FDA's first-line recommendation for ovulation induction in such cases is clomiphene citrate. Serial ultrasonography can be used to evaluate follicular development. Methodology The current study is a two-year prospective cohort study conducted at a tertiary care centre. One hundred patients with either primary or secondary infertility and no pelvic pathology were involved in the study and split into two groups: Group I included ovulatory women whose infertility was caused by a factor other than ovulatory disorder, and Group II comprised anovulatory women. Folliculometry was performed using transvaginal sonography; Group I had a spontaneous cycle, whereas Group II received clomiphene citrate (CC) to induce ovulation. The ovulation rate, pregnancy rate, multiple pregnancy rate, and rate of ovarian hyperstimulation (OHSS) were all studied. Results Seventy-two percent of the patients had primary infertility, and most appeared after 3-6 years of infertility. 62% of the patients were between the ages of 21 and 30 years. 50% of cases had ovulatory dysfunction, and polycystic ovarian disease (PCOD) was the most frequent cause of anovulation (24%). The leading follicular diameter was substantially bigger (22-26 mm) in the CC-triggered cycle compared to the spontaneous cycle (16-21 mm). In both spontaneous and induced cycles, the endometrial thickness displayed a linear development pattern during the pre-ovulatory phase and plateaued during the luteal phase. With CC, there was a 68% ovulation rate, a 32% pregnancy rate, a 12.5% multiple pregnancy rate, and a 2% incidence of OHSS. Conclusion Clomiphene citrate increases the rate of ovulation and pregnancy in females having ovulatory disorders.
PubMed: 37605698
DOI: 10.7759/cureus.42234