scholarly journals Sperm-oocyte interplay: an overview of spermatozoon’s role in oocyte activation and current perspectives in diagnosis and fertility treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Ishraq Zafar ◽  
Shi Lu ◽  
Honggang Li
Keyword(s):  
Diagnostic Tests ◽  
Scientific Information ◽  
Male Gamete ◽  
Fertility Treatment ◽  
Normal Embryo ◽  
Oocyte Activation ◽  
Fertilization Failure ◽  
Sperm Selection ◽  
Reproductive Techniques

AbstractThe fertilizing spermatozoon is a highly specialized cell that selects from millions along the female tract until the oocyte. The paternal components influence the oocyte activation during fertilization and are fundamental for normal embryo development; however, the sperm-oocyte interplay is in a continuous debate. This review aims to analyze the available scientific information related to the role of the male gamete in the oocyte activation during fertilization, the process of the interaction of sperm factors with oocyte machinery, and the implications of any alterations in this interplay, as well as the advances and limitations of the reproductive techniques and diagnostic tests. At present, both PLCζ and PAWP are the main candidates as oocyte activated factors during fertilization. While PLCζ mechanism is via IP3, how PAWP activates the oocyte still no clear, and these findings are important to study and treat fertilization failure due to oocyte activation, especially when one of the causes is the deficiency of PLCζ in the sperm. However, no diagnostic test has been developed to establish the amount of PLCζ, the protocol to treat this type of pathologies is broad, including treatment with ionophores, sperm selection improvement, and microinjection with PLCζ protein or RNA.

scholarly journals A novel homozygous mutation of phospholipase C zeta leading to defective human oocyte activation and fertilization failure

2020 ◽  
Vol 35 (4) ◽  
pp. 977-985 ◽  
Author(s):  
Peng Yuan ◽  
Cen Yang ◽  
Yixin Ren ◽  
Jie Yan ◽  
Yanli Nie ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Human Oocyte ◽  
Homozygous Mutation ◽  
Whole Genome ◽  
C2 Domain ◽  
Oocyte Activation ◽  
Fertilization Failure ◽  
Human Fertilization

Abstract STUDY QUESTION Is a novel homozygous phospholipase C zeta (PLCζ), c.1658 G>C; p. R553P mutation in the C2 domain associated with the outcomes of recurrent fertilization failure after ICSI? SUMMARY ANSWER PLCζ, c.1658 G>C led to defective human oocyte activation and fertilization failure, while this mutation in the C2 domain of PLCζ did not compromise concentration, motility and chromosome ploidy of sperm. WHAT IS KNOWN ALREADY Sperm-specific PLCζ is now widely considered to be the physiological stimulus that evokes intracellular calcium (Ca2+) oscillations, which are essential for egg activation during mammalian fertilization. Thus far, few genetic studies have shown that different point mutations in the PLCζ gene are associated with male infertility. STUDY DESIGN, SIZE, DURATION This was a basic medical research to assess pathogenicity for novel mutation in the C2 domain of PLCζ during human fertilization. PARTICIPANTS/MATERIALS, SETTING, METHODS Single-cell omics were applied to analyze the DNA methylation state of the fertilization failure oocytes and the ploidy of the patient’s sperm. Whole genome sequencing data for the patient were analyzed for mutations in PLCζ. Sanger sequencing confirmed the presence of a rare variant, and then the mutant and wild-type PLCζ mRNA were injected to observe oocyte activation. MAIN RESULTS AND THE ROLE OF CHANCE The fertilization failure oocytes (n = 4) were triploid and lacking proper DNA demethylation. The whole genome sequencing analysis revealed a novel missense homozygous mutation in PLCζ, c.1658 G>C; p. R553P, which leads to the conversion of arginine 553 to proline. This point mutation does not affect the production of the corresponding protein in sperm. However, microinjection of the mRNA transcribed from the PLCζ R553P mutation gene failed to trigger oocyte activation and the subsequent embryo development. LIMITATIONS, REASONS FOR CAUTION Only one patient with PLCζ mutations was available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS Notably, we discovered a novel homozygous mutation in PLCζ, which results in an abnormal conformation at the C2 domain of the PLCζ protein. Our findings indicate an essential role of PLCζ in human fertilization and the requirement of a normal structure of C2 domain in PLCζ-mediated physiological function. STUDY FUNDING/COMPETING INTEREST(S) This project is funded by the National Natural Science Foundation of China (31571544, 31871482, 31871447) and National Key Research and Development Program (2018YFC1004000, 2017YFA0103801). All authors declared no competing interests. TRIAL REGISTRATION NUMBER Not applicable.

Novel mutations in PLCZ1 cause male infertility due to fertilization failure or poor fertilization

2020 ◽  
Vol 35 (2) ◽  
pp. 472-481 ◽  
Author(s):  
Zheng Yan ◽  
Yong Fan ◽  
Fei Wang ◽  
Zhiguang Yan ◽  
Menghui Li ◽  
...  
Keyword(s):  
Male Infertility ◽  
Conflicts Of Interest ◽  
Missense Mutations ◽  
Oocyte Activation ◽  
Fertilization Failure ◽  
Novel Mutations ◽  
Primary Infertility ◽  
Human Fertilization ◽  
Poor Fertilization

Abstract STUDY QUESTION Do sperm-specific phospholipase C zeta (PLCZ1) mutations account for male infertility due to fertilization failure? SUMMARY ANSWER Six novel mutations and one reported mutation in PLCZ1 were identified in five of 14 independent families characterized by fertilization failure or poor fertilization, suggesting that these mutations may be responsible for fertilization failure in men exhibiting primary infertility. WHAT IS KNOWN ALREADY PLCZ1 is essential for the induction of intracellular calcium (Ca2+) oscillations and the initiation of oocyte activation during mammalian fertilization. However, genetic evidence linking PLCZ1 mutations with male infertility remains limited. STUDY DESIGN, SIZE, DURATION Fourteen unrelated primary infertility patients were recruited into this study from January 2016 to December 2018; the patients exhibited total fertilization failure or poor fertilization, as evidenced by ICSI and sperm-related oocyte activation deficiencies identified in mouse oocyte activation assays. PARTICIPANTS/MATERIALS, SETTING, METHODS Genomic DNA samples were extracted from the peripheral blood of patients. The whole exons of PLCZ1 were sequenced by Sanger sequencing. The PLCZ1 sequences were aligned by CodonCode software to identify rare variants. The ExAC database was used to search for the frequency of corresponding mutations. The pathogenicity of identified variants and their possible effects on the protein were assessed in silico. PLCZ1 protein levels in semen samples were evaluated by western blotting. Oocyte activation ability was assessed by the injection of wild-type and mutant PLCZ1 cRNAs into human mature metaphase II (MII) oocytes in vitro. MAIN RESULTS AND THE ROLE OF CHANCE We identified six novel mutations and one reported mutation in PLCZ1 among five affected individuals. In addition to four novel missense mutations, two new types of genetic variants were identified, including one in-frame deletion and one splicing mutation. Western blot analysis revealed that PLCZ1 protein expression was not observed in the semen samples from the five affected patients. Microinjection with the PLCZ1 cRNA variants was performed, and a significant decrease in the percentage of pronuclei was observed for four novel missense mutations and one novel in-frame deletion mutation, suggesting that these mutations have a deleterious influence on protein function. By artificial oocyte activation treatment, the fertilization failure phenotypes of four affected patients were successfully rescued and three healthy babies were delivered. LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION We screened only the whole exons of PLCZ1. Additional possible mutations in the non-coding region of PLCZ1 should be further studied. WIDER IMPLICATIONS OF THE FINDINGS Our study not only further confirms the important role of PLCZ1 in human fertilization but also expands the mutational spectrum of PLCZ1 associated with male infertility, which provides a basis for assessing genetic variation in PLCZ1 as a potential diagnostic marker for infertile men suffering from fertilization failure. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the National Natural Foundation of China (81 571 486 and 81 771 649). All authors have no conflicts of interest to declare.

scholarly journals Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape

2021 ◽  
Vol 9 (5) ◽  
pp. 899
Author(s):  
Anthony Torres-Ruesta ◽  
Rhonda Sin-Ling Chee ◽  
Lisa F.P. Ng
Keyword(s):  
Diagnostic Tests ◽  
Inflammatory Arthritis ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Chikv Infection ◽  
Wide Range ◽  
Susceptible Populations ◽  
Humoral Responses

Alphaviruses are mosquito-borne pathogens distributed worldwide in tropical and temperate areas causing a wide range of symptoms ranging from inflammatory arthritis-like manifestations to the induction of encephalitis in humans. Historically, large outbreaks in susceptible populations have been recorded followed by the development of protective long-lasting antibody responses suggesting a potential advantageous role for a vaccine. Although the current understanding of alphavirus antibody-mediated immunity has been mainly gathered in natural and experimental settings of chikungunya virus (CHIKV) infection, little is known about the humoral responses triggered by other emerging alphaviruses. This knowledge is needed to improve serology-based diagnostic tests and the development of highly effective cross-protective vaccines. Here, we review the role of antibody-mediated immunity upon arthritogenic and neurotropic alphavirus infections, and the current research efforts for the development of vaccines as a tool to control future alphavirus outbreaks.

Sperm Selection Technology in ART

2021 ◽  
Author(s):  
Catherine Martin ◽  
Emma Woodland
Keyword(s):  
Hyaluronic Acid ◽  
Live Birth ◽  
Plasma Membranes ◽  
Controlled Trial ◽  
Cochrane Review ◽  
Fertility Treatment ◽  
Future Research ◽  
Sperm Selection ◽  
Multicenter Randomized Controlled Trial

AbstractIntracytoplasmic sperm injection (ICSI) is a commonly used in vitro fertilization technique. Selection of sperm for injection is currently done using subjective assessment of morphology, which may not accurately identify the best-quality sperm. Hyaluronic acid receptors on sperm plasma membranes are a marker of maturity, and sperms which are capable of binding immobilized hyaluronic acid in vitro are of higher quality. This can be used as an advanced sperm selection technique to choose sperm for ICSI, termed physiological ICSI (PICSI). Several studies reported improved fertility treatment outcomes when using PICSI compared with conventional ICSI; however, the majority of studies are underpowered. Recently, a large, multicenter, randomized controlled trial, known as the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial, found a significant reduction in miscarriage rates with PICSI, but no significant effect on live birth rate. There are still many avenues through which PICSI may provide an advantage, subject to confirmation by future research, such as improved long-term health of offspring. Other advanced sperm selection techniques include intracytoplasmic morphologically selected sperm injection, magnetic-activated cell sorting, and Zeta potential sperm selection; however, the most recent Cochrane review concluded that there is currently insufficient evidence to ascertain whether these techniques improve clinical outcomes, such as live birth rates.

Evidence Based Medical Prevention: International Experience

2016 ◽  
pp. 34-37
Author(s):  
Olha Puzanovа
Keyword(s):  
Health Care ◽  
Preventive Medicine ◽  
Scientific Information ◽  
International Experience ◽  
Evidence Based ◽  
Task Forces ◽  
Cochrane Reviews ◽  
The Us ◽  
Based Medicine

The objective: was to study the international experience of evidence based preventive medicine development as well as to estimate its perspectives in Ukraine. Patients and methods. Main principles and methods of scientific knowledge and research have been used including universal ones, methods of systemic approach, quantitative and qualitative information analysis, classification and systematization of theoretical and empirical data, hystorical and logical methods, health statistics as well). In total 529 scientific information sources have been studied, particularly a number of evidence based medicine (EBM) computer databases, special task forces recommendations and Cochrane reviews on prevention, Register of medical and technological documents for health care standards in Ukraine et al. Results. The contribution of foreign scientific schools in the development of EBM has been determined, as well as the crucial role of scientific works carried out in the US and Great Britain in 1930–80s as to the development of evidence based preventive medicine. The international experience of the development and functioning of evidence based practice centers’ and special task forces on prevention has been summarized, as the experience of the development and implementation of recommendations on prevention in primary health care (PHC) in high income countries acceptable for Ukraine. The concept of evidence based prevention has been first proposed. It is revealed, that EBM implementation in Europe has been prioritized in both the field of infectious diseases prevention and PHC, while there are both the development of differentiated evidence based prevention and early evidence based diagnosis in PHC in the US. Conclusion. The results proved importance of taking into consideration of international experience while evidence based PHC is being developed as a priority in Ukraine.

Organization of school excursions in biology

2020 ◽  
Vol 04 (05) ◽  
pp. 39-32
Author(s):  
Gunay Isfandiyar Sadigov ◽  
Keyword(s):  
Teaching Methods ◽  
Scientific Information ◽  
Learning Technologies ◽  
Quality Of Education ◽  
Educational Work ◽  
Important Place ◽  
Methods Development ◽  
New Learning

The purpose of this article is to highlight the role of excursions in the lives of students and schoolchildren. The excursion is one of the main forms of educational work. The excursion is one of the main forms of educational work. The tour is conducted according to the school program. The tour is conducted in a group to make it more interesting. Excursions also contribute to the development of polytechnic education, as they give students the opportunity to get acquainted with production, use scientific information in industry and agriculture. From this it can be concluded that excursions occupy a very important place in the life of both schoolchildren and students. Key words: the process of teaching the method of excursion, the principle of vitality, teaching process, introduction of new learning technologies, quality of education, form of training, teaching methods, development and dissemination of the method

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