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Frontiers in Physiology 2023There has been a global decline in fertility rates, with ovulatory disorders emerging as the leading cause, contributing to a global lifetime infertility prevalence of... (Review)
Review
There has been a global decline in fertility rates, with ovulatory disorders emerging as the leading cause, contributing to a global lifetime infertility prevalence of 17.5%. Formation of the primordial follicle pool during early and further development of oocytes after puberty is crucial in determining female fertility and reproductive quality. However, the increasing exposure to environmental toxins (through occupational exposure and ubiquitous chemicals) in daily life is a growing concern; these toxins have been identified as significant risk factors for oogenesis in women. In light of this concern, this review aims to enhance our understanding of female reproductive system diseases and their implications. Specifically, we summarized and categorized the environmental toxins that can affect oogenesis. Here, we provide an overview of oogenesis, highlighting specific stages that may be susceptible to the influence of environmental toxins. Furthermore, we discuss the genetic and molecular mechanisms by which various environmental toxins, including metals, cigarette smoke, and agricultural and industrial toxins, affect female oogenesis. Raising awareness about the potential risks associated with toxin exposure is crucial. However, further research is needed to fully comprehend the mechanisms underlying these effects, including the identification of biomarkers to assess exposure levels and predict reproductive outcomes. By providing a comprehensive overview, this review aims to contribute to a better understanding of the impact of environmental toxins on female oogenesis and guide future research in this field.
PubMed: 37601637
DOI: 10.3389/fphys.2023.1219045 -
The EMBO Journal Dec 2023Recent studies have reported the differentiation of pluripotent cells into oocytes in vitro. However, the developmental competence of in vitro-generated oocytes remains...
Recent studies have reported the differentiation of pluripotent cells into oocytes in vitro. However, the developmental competence of in vitro-generated oocytes remains low. Here, we perform a comprehensive comparison of mouse germ cell development in vitro over all culture steps versus in vivo with the goal to understand mechanisms underlying poor oocyte quality. We show that the in vitro differentiation of primordial germ cells to growing oocytes and subsequent follicle growth is critical for competence for preimplantation development. Systematic transcriptome analysis of single oocytes that were subjected to different culture steps identifies genes that are normally upregulated during oocyte growth to be susceptible for misregulation during in vitro oogenesis. Many misregulated genes are Polycomb targets. Deregulation of Polycomb repression is therefore a key cause and the earliest defect known in in vitro oocyte differentiation. Conversely, structurally normal in vitro-derived oocytes fail at zygotic genome activation and show abnormal acquisition of 5-hydroxymethylcytosine on maternal chromosomes. Our data identify epigenetic regulation at an early stage of oogenesis limiting developmental competence and suggest opportunities for future improvements.
Topics: Female; Animals; Mice; Epigenesis, Genetic; Oocytes; Ovarian Follicle; Oogenesis; Germ Cells
PubMed: 37850882
DOI: 10.15252/embj.2023113955 -
Veterinary Sciences Jul 2023Cocaine is one of the most widely used drugs that, due to its molecular properties, causes various behavioral alterations, including sexual behavior. In vivo and in... (Review)
Review
Cocaine is one of the most widely used drugs that, due to its molecular properties, causes various behavioral alterations, including sexual behavior. In vivo and in vitro studies conducted mainly in mammals have shown various disorders of sexual activity and morpho-functional dysfunctions of the gonads in both sexes. Although the modalities are still unclear, cocaine has been shown to alter the cell cycle, induce apoptosis, and alter sperm motility. In females, this drug alters the formation of the meiotic spindle as well as may obstruct the ovulation mechanism of mature oocytes. The data provided in this review, in addition to reviewing the current literature on the main effects of cocaine on spermatogenesis and oogenesis mainly in mammals, will hopefully provide a basic overview that may help and support further future studies on the molecular interaction of cocaine and its metabolites with germ cells.
PubMed: 37624271
DOI: 10.3390/vetsci10080484 -
Cellular and Molecular Life Sciences :... Mar 2024Reproduction, a fundamental feature of all known life, closely correlates with energy homeostasis. The control of synthesizing and mobilizing lipids are dynamic and...
Reproduction, a fundamental feature of all known life, closely correlates with energy homeostasis. The control of synthesizing and mobilizing lipids are dynamic and well-organized processes to distribute lipid resources across tissues or generations. However, how lipid homeostasis is precisely coordinated during insect reproductive development is poorly understood. Here we describe the relations between energy metabolism and reproduction in the silkworm, Bombyx mori, a lepidopteran model insect, by using CRISPR/Cas9-mediated mutation analysis and comprehensively functional investigation on two major lipid lipases of Brummer (BmBmm) and hormone-sensitive lipase (BmHsl), and the sterol regulatory element binding protein (BmSrebp). BmBmm is a crucial regulator of lipolysis to maintain female fecundity by regulating the triglyceride (TG) storage among the midgut, the fat body, and the ovary. Lipidomics analysis reveals that defective lipolysis of females influences the composition of TG and other membrane lipids in the BmBmm mutant embryos. In contrast, BmHsl mediates embryonic development by controlling sterol metabolism rather than TG metabolism. Transcriptome analysis unveils that BmBmm deficiency significantly improves the expression of lipid synthesis-related genes including BmSrebp in the fat body. Subsequently, we identify BmSrebp as a key regulator of lipid accumulation in oocytes, which promotes oogenesis and cooperates with BmBmm to support the metabolic requirements of oocyte production. In summary, lipid homeostasis plays a vital role in supporting female reproductive success in silkworms.
Topics: Animals; Female; Bombyx; Oogenesis; Ovary; Embryonic Development; Lipids; Insect Proteins
PubMed: 38472536
DOI: 10.1007/s00018-024-05173-8 -
ELife Dec 2023Changes in the intracellular concentration of free calcium (Ca) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca release...
Changes in the intracellular concentration of free calcium (Ca) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca release is periodical, known as Ca oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IPR1). Another divalent cation, zinc (Zn), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn are indispensable for sperm-initiated Ca oscillations because Zn-deficient conditions induced by cell-permeable chelators abrogated Ca responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically or genetically generated eggs with lower levels of labile Zn displayed reduced IPR1 sensitivity and diminished ER Ca leak despite the stable content of the stores and IPR1 mass. Resupplying Zn restarted Ca oscillations, but excessive Zn prevented and terminated them, hindering IPR1 responsiveness. The findings suggest that a window of Zn concentrations is required for Ca responses and IPR1 function in eggs, ensuring optimal response to fertilization and egg activation.
Topics: Male; Animals; Mice; Oocytes; Semen; Oogenesis; Fertilization; Spermatozoa; Calcium; Calcium Signaling; Mammals
PubMed: 38099643
DOI: 10.7554/eLife.88082 -
ELife Nov 2023An animal's responses to environmental cues are critical for its reproductive program. Thus, a mechanism that allows the animal to sense and adjust to its environment...
An animal's responses to environmental cues are critical for its reproductive program. Thus, a mechanism that allows the animal to sense and adjust to its environment should make for a more efficient reproductive physiology. Here, we demonstrate that in specific sensory neurons influence onset of oogenesis through insulin signaling in response to food-derived cues. The chemosensory neurons ASJ modulate oogenesis onset through the insulin-like peptide (ILP) INS-6. In contrast, other sensory neurons, the olfactory neurons AWA, regulate food type-dependent differences in fertilization rates, but not onset of oogenesis. AWA modulates fertilization rates at least partly in parallel to insulin receptor signaling, since the insulin receptor DAF-2 regulates fertilization independently of food type, which requires ILPs other than INS-6. Together our findings suggest that optimal reproduction requires the integration of diverse food-derived inputs through multiple neuronal signals acting on the germline.
Topics: Animals; Caenorhabditis elegans; Insulin; Receptor, Insulin; Caenorhabditis elegans Proteins; Sensory Receptor Cells; Fertilization
PubMed: 37975568
DOI: 10.7554/eLife.83224 -
BioEssays : News and Reviews in... Oct 2023The ovarian reserve defines female reproductive lifespan, which in humans spans decades. The ovarian reserve consists of oocytes residing in primordial follicles...
The ovarian reserve defines female reproductive lifespan, which in humans spans decades. The ovarian reserve consists of oocytes residing in primordial follicles arrested in meiotic prophase I and is maintained independent of DNA replication and cell proliferation, thereby lacking stem cell-based maintenance. Largely unknown is how cellular states of the ovarian reserve are established and maintained for decades. Our recent study revealed that a distinct chromatin state is established during ovarian reserve formation in mice, uncovering a novel window of epigenetic programming in female germline development. We showed that an epigenetic regulator, Polycomb Repressive Complex 1 (PRC1), establishes a repressive chromatin state in perinatal mouse oocytes that is essential for prophase I-arrested oocytes to form the ovarian reserve. Here we discuss the biological roles and mechanisms underlying epigenetic programming in ovarian reserve formation, highlighting current knowledge gaps and emerging research areas in female reproductive biology.
Topics: Humans; Pregnancy; Female; Mice; Animals; Meiosis; Ovarian Reserve; Oocytes; Chromatin; Epigenesis, Genetic
PubMed: 37417392
DOI: 10.1002/bies.202300069 -
International Journal of Molecular... Dec 2023The oocyte transcriptome follows a tightly controlled dynamic that leads the oocyte to grow and mature. This succession of distinct transcriptional states determines... (Meta-Analysis)
Meta-Analysis Review
The oocyte transcriptome follows a tightly controlled dynamic that leads the oocyte to grow and mature. This succession of distinct transcriptional states determines embryonic development prior to embryonic genome activation. However, these oocyte maternal mRNA regulatory events have yet to be decoded in humans. We reanalyzed human single-oocyte RNA-seq datasets previously published in the literature to decrypt the transcriptomic reshuffles ensuring that the oocyte is fully competent. We applied trajectory analysis (pseudotime) and a meta-analysis and uncovered the fundamental transcriptomic requirements of the oocyte at any moment of oogenesis until reaching the metaphase II stage (MII). We identified a bunch of genes showing significant variation in expression from primordial-to-antral follicle oocyte development and characterized their temporal regulation and their biological relevance. We also revealed the selective regulation of specific transcripts during the germinal vesicle-to-MII transition. Transcripts associated with energy production and mitochondrial functions were extensively downregulated, while those associated with cytoplasmic translation, histone modification, meiotic processes, and RNA processes were conserved. From the genes identified in this study, some appeared as sensitive to environmental factors such as maternal age, polycystic ovary syndrome, cryoconservation, and in vitro maturation. In the future, the atlas of transcriptomic changes described in this study will enable more precise identification of the transcripts responsible for follicular growth and oocyte maturation failures.
Topics: Female; Humans; Pregnancy; Cell Nucleus; Gene Expression Profiling; Oocytes; Oogenesis; Transcriptome
PubMed: 38203203
DOI: 10.3390/ijms25010033 -
Reproductive Sciences (Thousand Oaks,... May 2024This paper will review a remarkable new approach to in vitro maturation "IVM" of oocytes from ovarian tissue, based on our results with in vitro oogenesis from somatic... (Review)
Review
This paper will review a remarkable new approach to in vitro maturation "IVM" of oocytes from ovarian tissue, based on our results with in vitro oogenesis from somatic cells. As an aside benefit we also have derived a better understanding of ovarian longevity from ovary transplant. We have found that primordial follicle recruitment is triggered by tissue pressure gradients. Increased pressure holds the follicle in meiotic arrest and prevents recruitment. Therefore recruitment occurs first in the least dense inner tissue of the cortico-medullary junction. Many oocytes can be obtained from human ovarian tissue and mature to metaphase 2 in vitro with no need for ovarian stimulation. Ovarian stimulation may only be necessary for removing the oocyte from the ovary, but this can also be accomplished by simple dissection at the time of ovary tissue cryopreservation. By using surgical dissection of the removed ovary, rather than a needle stick, we can obtain many oocytes from very small follicles not visible with ultrasound. A clearer understanding of ovarian function has come from in vitro oogenesis experiments, and that explains why IVM has now become so simple and robust. Tissue pressure (and just a few "core genes" in the mouse) direct primordial follicle recruitment and development to mature oocyte, and therefore also control ovarian longevity. There are three distinct phases to oocyte development both in vitro and in vivo: in vitro differentiation "IVD" which is not gonadotropin sensitive (the longest phase), in vitro gonadotropin sensitivity "IVG" which is the phase of gonadotropin stimulation to prepare for meiotic competence, and IVM to metaphase II. On any given day 35% of GVs in ovarian tissue have already undergone "IVD" and "IVG" in vivo, and therefore are ready for IVM.
Topics: Female; Animals; Oogenesis; Humans; Ovary; In Vitro Oocyte Maturation Techniques; Oocytes; Ovarian Follicle; Mice
PubMed: 38160209
DOI: 10.1007/s43032-023-01427-1 -
Cells Jan 2024Oogenesis is a developmental process leading to the formation of an oocyte, a haploid gamete, which upon fertilisation and sperm entry allows the male and the female... (Review)
Review
Oogenesis is a developmental process leading to the formation of an oocyte, a haploid gamete, which upon fertilisation and sperm entry allows the male and the female pronuclei to fuse and give rise to a zygote. In addition to forming a haploid gamete, oogenesis builds up a store of proteins, mRNAs, and organelles in the oocyte needed for the development of the future embryo. In several species, such as , the polarity axes determinants of the future embryo must be asymmetrically distributed prior to fertilisation. In the oocyte, the correct positioning of the nucleus is essential for establishing the dorsoventral polarity axis of the future embryo and allowing the meiotic spindles to be positioned in close vicinity to the unique sperm entry point into the oocyte.
Topics: Animals; Male; Female; Drosophila; Semen; Oogenesis; Oocytes; Cell Nucleus
PubMed: 38275826
DOI: 10.3390/cells13020201