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Journal of Biosciences 2024We have extensively described that the neoplastic process (NP) has deep evolutionary roots and we have made specific predictions about the connection between cancer and... (Review)
Review
We have extensively described that the neoplastic process (NP) has deep evolutionary roots and we have made specific predictions about the connection between cancer and the formation of the first embryo, which allowed for the evolutionary radiation of metazoans. My main hypothesis is that the NP is at the heart of cellular mechanisms responsible for animal morphogenesis, and given its embryological basis, also at the center of cell differentiation-one of the most interesting and relevant aspects of embryogenesis. In this article, I take forward the idea of the role of physics in the modeling of the neoplastic functional module (NFM) and its contribution to morphogenesis to reveal the totipotency of the zygote. In my consideration of these arguments, I examine mechanical and biophysical clues and their intimate connection with cellular differentiation. I expound on how cancer biology is perfectly intertwined with embryonic differentiation and why it is considered a disease of cell differentiation. The neoplasia is controlled by textural gradients that lead to cell differentiation within the embryo. Thus, the embryo would be a benign tumor. Finally, inspired by evolutionary history and by what the nervous system represents for current biology and based on the impressive nervous system of ctenophores as seen in fossil records, I propose a hypothesis with physical foundations (mechanical morphogenesis) for the formation of a preneural pattern of the nervous system of the first animal embryo.
Topics: Animals; Cell Differentiation; Morphogenesis; Neoplasms; Embryonic Development; Phylogeny; Humans; Biological Evolution; Zygote
PubMed: 38864237
DOI: No ID Found -
ELife Jun 2024Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with...
Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However, -knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by an unknown factor(s). Here, we present multiple lines of evidence that the multicopy homeobox gene, , encodes a transcription factor that is highly expressed in mouse two-cell embryos and redundantly drives ZGA. Genome-wide profiling revealed that OBOX4 specifically binds and activates MERVL LTRs as well as a subset of murine endogenous retroviruses with lysine tRNA primer (MERVK) LTRs. Depletion of is tolerated by embryogenesis, whereas concomitant / depletion markedly compromises embryonic development. Our study identified OBOX4 as a transcription factor that provides genetic redundancy to preimplantation development.
Topics: Animals; Homeodomain Proteins; Zygote; Mice; Embryonic Development; Gene Expression Regulation, Developmental; Genome; Mice, Knockout
PubMed: 38856708
DOI: 10.7554/eLife.95856 -
Ecotoxicology and Environmental Safety Jul 2024Air pollution is widely acknowledged as a significant risk factor for human health, especially reproductive health. Nevertheless, many studies have disregarded the...
Air pollution is widely acknowledged as a significant risk factor for human health, especially reproductive health. Nevertheless, many studies have disregarded the potentially mixed effects of air pollutants on reproductive outcomes. We performed a retrospective cohort study involving 8048 women with 9445 cycles undergoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) in China, from 2017 to 2021. A land-use random forest model was applied to estimate daily residential exposure to air pollutants, including sulfur dioxide (SO), nitrogen dioxide (NO), carbon monoxide (CO), ozone (O), and fine particulate matter (PM). Individual and joint associations between air pollutants and oocyte-related outcomes of ART were evaluated. In 90 days prior to oocyte pick-up to oocyte pick-up (period A), NO, O and CO was negatively associated with total oocyte yield. In the 90 days prior to oocyte pick-up to start of gonadotropin medication (Gn start, period B), there was a negative dose-dependent association of exposure to five air pollutants with total oocyte yield and mature oocyte yield. In Qgcomp analysis, increasing the multiple air pollutants mixtures by one quartile was related to reducing the number of oocyte pick-ups by -2.00 % (95 %CI: -2.78 %, -1.22 %) in period A, -2.62 % (95 %CI: -3.40 %, -1.84 %) in period B, and -0.98 % (95 %CI: -1.75 %, -0.21 %) in period C. During period B, a 1-unit increase in the WQS index of multiple air pollutants exposure was associated with fewer number of total oocyte (-1.27 %, 95 %CI: -2.16 %, -0.36 %) and mature oocyte (-1.42 %, 95 %CI: -2.41 %, -0.43 %). O and NO were major contributors with adverse effects on the mixed associations. Additionally, period B appears to be the susceptible window. Our study implies that exposure to air pollution adversely affects oocyte-related outcomes, which raises concerns about the potential adverse impact of air pollution on women's reproductive health.
Topics: Female; Humans; Air Pollutants; Retrospective Studies; Oocytes; Adult; China; Reproductive Techniques, Assisted; Air Pollution; Ozone; Particulate Matter; Environmental Exposure; Fertilization in Vitro; Cohort Studies; Nitrogen Dioxide
PubMed: 38852468
DOI: 10.1016/j.ecoenv.2024.116525 -
Ecotoxicology and Environmental Safety Jul 2024Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that...
Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that BDE-209 has a destructive effect on the reproductive system of mammals. However, the effect of BDE-209 exposure on oocyte quality and whether there is a viable salvage strategy have not been reported. Here, we report that murine oocytes exposed to BDE-209 produce a series of meiostic defects, including increased fragmentation rates and decreased PBE. Furthermore, exposure of oocytes to BDE-209 hinders mitochondrial function and disrupts mitochondrial integrity. Our observations show that supplementation with NMN successfully alleviated the meiosis impairment caused by BDE-209 and averted oocyte apoptosis by suppressing ROS generation. In conclusion, our findings suggest that NMN supplementation may be able to alleviate the oocyte quality impairment induced by BDE-209 exposure, providing a potential strategy for protecting oocytes from environmental pollutant exposure.
Topics: Animals; Halogenated Diphenyl Ethers; Oocytes; Mice; Reactive Oxygen Species; Female; Apoptosis; Mitochondria; Environmental Pollutants; Meiosis; Flame Retardants
PubMed: 38850695
DOI: 10.1016/j.ecoenv.2024.116557 -
BMC Veterinary Research Jun 2024Buffalo spermatozoa have a distinct membrane structure that makes them more vulnerable to cryopreservation, resulting in lower-quality post-thawed sperm. This decreases... (Comparative Study)
Comparative Study
Effect of autologous platelet-rich plasma on the fertility and quality of cryopreserved buffalo bull semen: a comparative study using OptiXcell® and tris egg yolk extenders.
BACKGROUND
Buffalo spermatozoa have a distinct membrane structure that makes them more vulnerable to cryopreservation, resulting in lower-quality post-thawed sperm. This decreases the success rate of artificial insemination in buffaloes. Understanding and addressing these specific vulnerabilities are essential for improving reproductive techniques in buffalo populations. The properties of cryopreserved buffalo bull semen were examined in this study regarding the impact of adding autologous platelet-rich plasma (PRP) to OptiXcell® or Tris egg yolk-based extenders. Ten buffalo bulls were used to collect semen. Each bull's ejaculate was separated into two main equal amounts, each of which was then diluted with either OptiXcell® or Tris egg yolk-based extender, supplemented with various PRP concentrations (5%, 10%, and 15%), and the control (0%), before being cryopreserved according to established protocols. Following equilibration and thawing, the quality and functionality of the sperm were evaluated, along with the antioxidant enzyme activities (GSH and TAC), malondialdehyde (MDA) content, and in vivo fertilization rate of the thawed semen.
RESULTS
All PRP concentrations in both extenders, particularly 10% PRP, improved the quality and functionality of the sperm in both equilibrated and frozen-thawed semen. Additionally, the antioxidant enzyme activities in both extenders were higher in the PRP-supplemented groups compared to the control group in thawed semen (P < 0.05). All post-thaw sperm quality, antioxidant enzyme activities, and functionality aside from DNA integrity were higher (P < 0.05) in the PRP-supplemented OptiXcell® than in the PRP-supplemented Tris egg yolk-based extender. The fertility of cryopreserved semen in the extenders supplemented with 10% and 15% PRP increased (P < 0.05) significantly more than that of the control extenders, with 10% PRP being the optimum concentration in OptiXcell® (80%) compared to that of Tris egg yolk-based extender (66.67%) and control of two extenders (53.33% and 46.67%, respectively).
CONCLUSIONS
Even though autologous PRP-supplemented extenders have a protective impact on equilibrated and cryopreserved semen, 10% PRP-supplemented OptiXcell® extenders are more effective at preserving post-thaw semen quality, functionality, and antioxidant capacity, which increases the in vivo fertility of buffalo bulls.
Topics: Animals; Buffaloes; Male; Cryopreservation; Semen Preservation; Platelet-Rich Plasma; Fertility; Egg Yolk; Semen Analysis; Cryoprotective Agents; Insemination, Artificial; Female; Semen; Spermatozoa
PubMed: 38849855
DOI: 10.1186/s12917-024-04022-x -
Reproductive Biology and Endocrinology... Jun 2024Ovarian stimulation (OS) with high daily gonadotropin doses are commonly offered to patients attempting social/elective egg freezing. However, the optimal daily...
OBJECTIVE
Ovarian stimulation (OS) with high daily gonadotropin doses are commonly offered to patients attempting social/elective egg freezing. However, the optimal daily gonadotropin dose that would allow a higher oocyte yield in the successive IVF cycle attempt was not settled and should be determined.
PATIENTS AND METHODS
Data from all women admitted to our IVF unit for social/EEF, who underwent two consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300IU were analyzed. Patients characteristics and OS variables were used in an attempt to build a logistic model, helping in determining the daily gonadotropin dose that should be offered to patient during their second EEF attempt, aiming to further increase their oocyte yield.
RESULTS
Three hundred and thirteen consecutive women undergoing two successive IVF cycle attempts were evaluated. Using logistic regression model, two equations were developed using individual patient-level data that determine the daily gonadotropin dose needed aiming to increase the oocyte yield in the successive cycle. (a): X=-0.514 + 2.87*A1 + 1.733*A2-0.194* (E2/1000) and (b): P = EXP(X) / [1 + EXP(X)].
CONCLUSIONS
Using the aforementioned equations succeeded in determining the daily gonadotropin dose that might result in increasing oocyte yield, with an AUC of 0.85. Any additional oocyte retrieved to these EEF patients might get them closer to fulfil their desire to parenthood.
Topics: Humans; Female; Adult; Ovulation Induction; Oocytes; Fertilization in Vitro; Pregnancy; Oocyte Retrieval; Cryopreservation; Gonadotropins; Dose-Response Relationship, Drug; Retrospective Studies; Pregnancy Rate; Logistic Models
PubMed: 38844947
DOI: 10.1186/s12958-024-01236-4 -
BMC Pregnancy and Childbirth Jun 2024The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this...
BACKGROUND
The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients.
METHODS
Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4-6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained.
RESULTS
Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94-14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24-14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23-8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4-6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively.
CONCLUSIONS
Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4-6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes' cytoplasm from P-ICSI varied that from R-ICSI.
Topics: Humans; Sperm Injections, Intracytoplasmic; Female; Pregnancy; Adult; Oocytes; Embryonic Development; In Vitro Oocyte Maturation Techniques; Time Factors; Prospective Studies; Prognosis; Pregnancy Rate; Oocyte Retrieval; Embryo Transfer; Blastocyst; Embryo Culture Techniques; Polar Bodies
PubMed: 38844840
DOI: 10.1186/s12884-024-06577-x -
Nature Jun 2024Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs), which influences offspring development and adult phenotypes. Whether...
Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs), which influences offspring development and adult phenotypes. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
Topics: Animals; Male; Spermatozoa; Mice; RNA, Mitochondrial; Female; Epigenesis, Genetic; Diet, High-Fat; Humans; RNA, Transfer; Epididymis; Testis; RNA, Small Untranslated; Mitochondria; Obesity; Oocytes; Embryo, Mammalian; Fertilization; Overweight; Mice, Inbred C57BL; Paternal Inheritance
PubMed: 38839949
DOI: 10.1038/s41586-024-07472-3 -
Fertility and Sterility Jun 2024To demonstrate clinical techniques for in vitro maturation (IVM) treatment, including stimulation recommendations, small follicle pick-up procedures, and compact...
OBJECTIVE
To demonstrate clinical techniques for in vitro maturation (IVM) treatment, including stimulation recommendations, small follicle pick-up procedures, and compact cumulus-oocyte complex (COC) search practice.
DESIGN
This video utilizes live-action footage from surgery and embryology practice for a representative IVM treatment cycle, with step-by-step instructions and recommendations for practice procedures.
SETTING
In vitro fertilization (IVF) clinic.
PATIENT(S)
Patients undergoing IVM treatment. The patient(s) included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites.
INTERVENTION(S)
Identification of treatment cohorts, IVM definitions, and recommendations for stimulation treatments. A visual demonstration of COC extraction techniques from small antral follicles includes tubing, needle types, considerations when using double lumen or sheath needles, needle pressure, ultrasound, needle flushing, and aspiration technique. Visual demonstration of oocyte search and IVM preparation, including filtering follicular aspirate, prevention of COC cooling, identification of compact COCs, and general parameters of different IVM approaches.
MAIN OUTCOME MEASURE(S)
Clinical techniques for small follicle ovum pick up and compact COC identification for IVM treatment.
RESULTS
Successful IVM treatment of patients can be achieved using minimal ovarian stimulation, effective small follicle retrieval, and efficient compact COC identification with flexibility in approach depending on clinical constraints and preference.
CONCLUSION(S)
In vitro maturation treatment is an efficacious and safe treatment for high ovarian reserve and hyper-responding patients undergoing IVF treatment, in which the retrieval of multiple immature COCs and their ex vivo maturation can be achieved with little to no in vivo stimulation. Practice procedures vary between treatment centers and IVM techniques. This video provides practice recommendations paired with a visual demonstration of techniques to assist in standardizing the approach and expanding the practice to more centers.
PubMed: 38838807
DOI: 10.1016/j.fertnstert.2024.05.164 -
Frontiers in Cellular and Infection... 2024The rabies virus enters the nervous system by interacting with several molecular targets on host cells to modify behavior and trigger receptor-mediated endocytosis of...
The rabies virus enters the nervous system by interacting with several molecular targets on host cells to modify behavior and trigger receptor-mediated endocytosis of the virion by poorly understood mechanisms. The rabies virus glycoprotein (RVG) interacts with the muscle acetylcholine receptor and the neuronal α4β2 subtype of the nicotinic acetylcholine receptor (nAChR) family by the putative neurotoxin-like motif. Given that the neurotoxin-like motif is highly homologous to the α7 nAChR subtype selective snake toxin α-bungarotoxin (αBTX), other nAChR subtypes are likely involved. The purpose of this study is to determine the activity of the RVG neurotoxin-like motif on nAChR subtypes that are expressed in brain regions involved in rabid animal behavior. nAChRs were expressed in oocytes, and two-electrode voltage clamp electrophysiology was used to collect concentration-response data to measure the functional effects. The RVG peptide preferentially and completely inhibits α7 nAChR ACh-induced currents by a competitive antagonist mechanism. Tested heteromeric nAChRs are also inhibited, but to a lesser extent than the α7 subtype. Residues of the RVG peptide with high sequence homology to αBTX and other neurotoxins were substituted with alanine. Altered RVG neurotoxin-like peptides showed that residues phenylalanine 192, arginine 196, and arginine 199 are important determinants of RVG peptide apparent potency on α7 nAChRs, while serine 195 is not. The evaluation of the rabies ectodomain reaffirmed the observations made with the RVG peptide, illustrating a significant inhibitory impact on α7 nAChR with potency in the nanomolar range. In a mammalian cell culture model of neurons, we confirm that the RVG peptide binds preferentially to cells expressing the α7 nAChR. Defining the activity of the RVG peptide on nAChRs expands our understanding of basic mechanisms in host-pathogen interactions that result in neurological disorders.
Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Rabies virus; Humans; Xenopus laevis; Glycoproteins; Oocytes; Viral Proteins; Viral Envelope Proteins; Host-Pathogen Interactions; Protein Binding; Rabies; Acetylcholine; Neurotoxins
PubMed: 38836054
DOI: 10.3389/fcimb.2024.1394713