Novel variants in <scp><i>ACTL7A</i></scp> and <scp><i>PLCZ1</i></scp> are associated with male infertility and total fertilization failure

Zhao, Shuai; Cui, Ying; Shunli, Guo; Liu, Boyang; Bian, Yuehong; Zhao, Shigang; Chen, Zi‐Jiang; Zhao, Han

doi:10.1111/cge.14293

Cited by 9 publications

(2 citation statements)

References 10 publications

(19 reference statements)

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“…Those results are consistent with our study, couples with OAT can benefit from ICSI-AOA in terms of higher fertilization rate, which in turn increases the number of available embryos and may improve the implantation and pregnancy rates. Recent researches found novel sperm-related oocyte activators, which showed that the ACTL7A/PLCZ1 mutation and DPY19 deletion decreased the expression of functional PLCζ, resulting in acrosomal detachment and oocyte activation failure associated with male infertility, and ICSI-AOA could rescue TFF in individuals with the ACTL7A/PLCZ1/DPY19 pathogenic variants ( 9 , 25 , 26 ). However, ICSI-AOA is not always beneficial for patients with previous LFR and a suspected oocyte-related activation deficiency ( 27 ), except Vanden Meerschaut F et al.…”

Section: Discussionmentioning

confidence: 99%

“…Neonatal characteristics in the AOA group. decreased the expression of functional PLCz, resulting in acrosomal detachment and oocyte activation failure associated with male infertility, and ICSI-AOA could rescue TFF in individuals with the ACTL7A/PLCZ1/DPY19 pathogenic variants(9,25,26). However, ICSI-AOA is not always beneficial for patients with previous LFR and a suspected oocyte-related activation deficiency(27), except Vanden Meerschaut F et al reported that ICSI-AOA was very efficient in patients with a suspected oocyte-related activation deficiency and previous TFF after conventional ICSI.…”

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Artificial oocyte activation with Ca2+ ionophore improves reproductive outcomes in patients with fertilization failure and poor embryo development in previous ICSI cycles

Ruan,

Liang,

Pan

et al. 2023

Front. Endocrinol.

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Research questionDoes artificial oocyte activation (AOA) by a calcium ionophore (ionomycin) improve the previous fertilization failure or poor embryo development of intracytoplasmic sperm injection (ICSI) account for male factor infertility or other infertility causes?DesignThis retrospective study involved 114 patients receiving ICSI-AOA in Shanghai First Maternity and Infant Hospital with previous ICSI fertilization failure or poor embryo development. The previous ICSI cycles of the same patients without AOA served as the control group. The fertilization rates, cleavage rates, transferable embryo rates and blastocyst formation rates of the two groups were compared. Additionally, the clinical pregnancy, implantation rate and live birth rates were also compared to assess the efficiency and safety of AOA. Furthermore, two subgroup analyses were performed in this study based on the cause of infertility and the reason for AOA. The fertilization rate, embryonic development potential and clinical outcome were compared among groups.ResultsAmong 114 ICSI-AOA cycles, the fertilization rate, top-quality embryo rate, implantation rate, clinical pregnancy per patient and live birth rate per patient were improved significantly compared with previous ICSI cycles (p<0.05 to P< 0.001), and the miscarriage rate in the AOA group was significantly lower than that of the control group (p<0.001). In the AOA subgroups based on the cause of infertility, the fertilization rates of each subgroup were significantly improved compared with previous control cycles except for the mixed factor infertility subgroup (p<0.05 to p<0.001). In the AOA subgroups based on the reason for AOA, the fertilization rates of each subgroup were significantly increased compared with those in their previous ICSI cycle without AOA (p<0.001); however, there was no significant difference in the top-quality embryo rate. No significant improvement was found in the implantation rates and the clinical pregnancy rate in each subgroup except for the poor embryo development subgroup. In the 114 AOA cycles, 35 healthy infants (21 singletons and 7 twins) were delivered without major congenital birth defects or malformations.ConclusionThis study showed that AOA with the calcium ionophore ionomycin can improve the reproductive outcomes of patients with previous fertilization failure and poor embryo development after ICSI.

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Artificial oocyte activation with Ca2+ ionophore improves reproductive outcomes in patients with fertilization failure and poor embryo development in previous ICSI cycles

Ruan,

Liang,

Pan

et al. 2023

Front. Endocrinol.

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Deficiency of MFSD6L, an acrosome membrane protein, causes oligoasthenoteratozoospermia in humans and mice

Zhou,

Wu,

Wang

et al. 2024

Journal of Genetics and Genomics

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Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review

Wei,

Wang,

et al. 2023

Human Reproduction Update

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BACKGROUND Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments. OBJECTIVE AND RATIONALE The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment. SEARCH METHODS PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed. OUTCOMES A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment. WIDER IMPLICATIONS The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1), actin-like7A (ACTL7A), actin-like 9 (ACTL9), and IQ motif-containing N (IQCN), ICSI may also fail to fertilize. We can consider artificial oocyte activation technology with ICSI to improve fertilization rate and reduce monetary and time costs. In the future, fertility is expected to be improved or restored by interfering with or supplementing the relevant genes.

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Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure

Cited by 9 publications

References 10 publications

Artificial oocyte activation with Ca2+ ionophore improves reproductive outcomes in patients with fertilization failure and poor embryo development in previous ICSI cycles

Artificial oocyte activation with Ca2+ ionophore improves reproductive outcomes in patients with fertilization failure and poor embryo development in previous ICSI cycles

Deficiency of MFSD6L, an acrosome membrane protein, causes oligoasthenoteratozoospermia in humans and mice

Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review

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