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Article ; Online: Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes.

Sun, Si-Min / Zhao, Bing-Wang / Li, Yuan-Yuan / Liu, Hong-Yang / Xu, Yuan-Hong / Yang, Xue-Mei / Guo, Jia-Ni / Ouyang, Ying-Chun / Weng, Chang-Jiang / Guan, Yi-Chun / Sun, Qing-Yuan / Wang, Zhen-Bo

Development (Cambridge, England)

2024 Volume 151, Issue 6

Abstract: The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin- ... ...

Abstract	The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.
MeSH term(s)	Animals ; Female ; Mice ; Anaphase-Promoting Complex-Cyclosome/genetics ; Anaphase-Promoting Complex-Cyclosome/metabolism ; M Phase Cell Cycle Checkpoints ; Meiosis ; Oocytes/metabolism ; Ubiquitins/metabolism
Chemical Substances	Anaphase-Promoting Complex-Cyclosome (EC 2.3.2.27) ; Ubiquitins ; Ube2s protein, mouse (EC 2.3.2.23)
Language	English
Publishing date	2024-03-28
Publishing country	England
Document type	Journal Article
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.202285
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Article ; Online: Insights into the adverse effects of prepubertal chronic ethanol exposure on adult female reproduction.

Li, Qian-Nan / Hou, Guan-Mei / Sun, Si-Min / Liu, Wen-Bo / Meng, Tie-Gang / Hou, Yi / Schatten, Heide / Sun, Qing-Yuan / Ou, Xiang-Hong

Aging

2023 Volume 15, Issue 13, Page(s) 6292–6301

Abstract: Heavy drinking in women is known to adversely affect pregnancy and fertility. However, pregnancy is a complex process, and the adverse effects of ethanol on pregnancy does not mean that ethanol will have adverse effects on all stages from gamete to fetal ...

Abstract	Heavy drinking in women is known to adversely affect pregnancy and fertility. However, pregnancy is a complex process, and the adverse effects of ethanol on pregnancy does not mean that ethanol will have adverse effects on all stages from gamete to fetal formation. Similarly, the adverse effects of ethanol before and after adolescence cannot be generalized. To focus on the effects of prepubertal ethanol on female reproductive ability, we established a mouse model of prepubertal ethanol exposure by changing drinking water to 20% v/v ethanol. Some routine detections were performed on the model mice, and details such as mating, fertility, reproductive organ and fetal weights were recorded day by day after discontinuation of ethanol exposure. Prepubertal ethanol exposure resulted in decreased ovarian weight and significantly reduced oocyte maturation and ovulation after sexual maturation, however, normal morphology oocytes with discharged polar body showed normal chromosomes and spindle morphology. Strikingly, oocytes with normal morphology from ethanol exposed mice showed reduced fertilization rate, but once fertilized they had the ability to develop to blastocysts. RNA-seq analysis showed that the gene expression of the ethanol exposed oocytes with normal morphology had been altered. These results show the adverse effects of prepubertal alcohol exposure on adult female reproductive health.
MeSH term(s)	Pregnancy ; Female ; Mice ; Animals ; Ethanol/toxicity ; Reproduction ; Oocytes ; Fertility ; Germ Cells
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204851
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Article ; Online: SRSF2 is required for mRNA splicing during spermatogenesis.

Lei, Wen-Long / Du, Zongchang / Meng, Tie-Gang / Su, Ruibao / Li, Yuan-Yuan / Liu, Wenbo / Sun, Si-Min / Liu, Meng-Yu / Hou, Yi / Zhang, Chun-Hui / Gui, Yaoting / Schatten, Heide / Han, Zhiming / Liu, Chenli / Sun, Fei / Wang, Zhen-Bo / Qian, Wei-Ping / Sun, Qing-Yuan

BMC biology

2023 Volume 21, Issue 1, Page(s) 231

Abstract: Background: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited.: Results: Here, we report that Serine/ ... ...

Abstract	Background: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Results: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Conclusions: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.
MeSH term(s)	Male ; Humans ; Spermatogenesis/genetics ; RNA Splicing ; RNA-Binding Proteins/genetics ; Alternative Splicing ; Meiosis/genetics ; RNA, Messenger
Chemical Substances	RNA-Binding Proteins ; RNA, Messenger
Language	English
Publishing date	2023-10-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-023-01736-6
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Article ; Online: Perinatal outcomes of singleton live births after preimplantation genetic testing during single frozen-thawed blastocyst transfer cycles: a propensity score-matched study.

Zheng, Wei / Yang, Shu Heng / Yang, Chen / Ren, Bing Nan / Sun, Si Min / Liu, Yan Li / Yang, Ru Jing / Lou, Hua / Zhang, Lin Lin / Guan, Yi Chun

Fertility and sterility

2022 Volume 117, Issue 3, Page(s) 562–570

Abstract: Objective: To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton ... ...

Abstract	Objective: To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton pregnancy. Design: A retrospective cohort study. Setting: A university-affiliated fertility center. Patient(s): This cohort study included singleton live births resulting from PGT (n = 232) and IVF/ICSI singleton pregnancies (n = 2,829) with single frozen-thawed blastocyst transfer. Multiple baseline covariates were used for propensity score matching, yielding 214 PGT singleton pregnancies matched to 617 IVF/ICSI singleton pregnancies. Intervention(s): Trophectoderm biopsy. Main outcome measure(s): The primary outcome was gestational hypertension, and various clinical perinatal secondary outcomes related to maternal and neonatal health were measured. Result(s): Compared with IVF/ICSI singleton pregnancy, PGT singleton pregnancy was associated with a significantly higher risk of gestational hypertension (adjusted odds ratio, 2.58; 95% confidence interval, 1.32, 5.05). In the matched sample, the risk of gestational hypertension remained higher with PGT singleton pregnancy (odds ratio, 2.33; 95% confidence interval, 1.04, 5.22) than with IVF/ICSI singleton pregnancy. No statistical differences were noted in any other measured outcomes between the groups. Conclusion(s): The perinatal outcomes of PGT and IVF/ICSI singleton pregnancies were similar except for the observed potentially higher risk of gestational hypertension with PGT singleton pregnancy. However, because the data on PGT singleton pregnancies are limited, this conclusion warrants further investigation.
MeSH term(s)	Adult ; Cohort Studies ; Cryopreservation/methods ; Cryopreservation/trends ; Embryo Transfer/methods ; Embryo Transfer/trends ; Female ; Fertilization in Vitro ; Freezing ; Genetic Testing/methods ; Genetic Testing/trends ; Humans ; Hypertension, Pregnancy-Induced/diagnosis ; Hypertension, Pregnancy-Induced/epidemiology ; Infant, Newborn ; Live Birth/epidemiology ; Male ; Pregnancy ; Preimplantation Diagnosis/methods ; Preimplantation Diagnosis/trends ; Propensity Score ; Retrospective Studies
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80133-1
ISSN	1556-5653 ; 0015-0282
ISSN (online)	1556-5653
ISSN	0015-0282
DOI	10.1016/j.fertnstert.2021.12.020
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Article ; Online: MAPRE2 regulates the first meiotic progression in mouse oocytes.

Li, Yuan-Yuan / Lei, Wen-Long / Zhang, Chang-Fa / Sun, Si-Min / Zhao, Bing-Wang / Xu, Ke / Hou, Yi / Ouyang, Ying-Chun / Wang, Zhen-Bo / Guo, Lei / Sun, Qing-Yuan / Han, Zhiming

Experimental cell research

2022 Volume 416, Issue 1, Page(s) 113135

Abstract: Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, cell migration and morphogenesis. Microtubule- ... ...

Abstract	Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, cell migration and morphogenesis. Microtubule-associated RP/EB family member 2 (MAPRE2/EB2) is a highly conserved core component of +TIPs networks, but whether this molecule is required for mammalian meiotic progression is unknown. In this study, we investigated the expression and function of MAPRE2 during oocyte maturation. Our results showed that MAPRE2 was consistently expressed from germinal vesicle (GV) to metaphase II (MII) stages and that MAPRE2 was distributed in the cytoplasm of oocytes at GV stage and along the spindle at metaphase I (MI) and MII stages. Small interfering RNA-mediated knockdown of Mapre2 severely impaired microtubule stability, kinetochore-microtubule attachment, and chromosome alignment and subsequently caused spindle assembly checkpoint (SAC) activation and cyclin B1 nondegradation, leading to failure of chromosome segregation and first polar body extrusion. This study demonstrates for the first time that MAPRE2 plays an important role during mouse oocyte meiosis.
MeSH term(s)	Animals ; Chromosome Segregation ; Mammals ; Meiosis ; Metaphase ; Mice ; Oocytes/metabolism ; Spindle Apparatus/metabolism
Language	English
Publishing date	2022-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2022.113135
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Article: The methylation status in GNAS clusters May Be an epigenetic marker for oocyte quality

Li, Qian-Nan / Li, Ang / Sun, Si-Min / Liu, Wen-Bo / Meng, Tie-Gang / Guo, Xing-Ping / Schatten, Heide / Sun, Qing-Yuan / Ou, Xiang-Hong

Biochemical and biophysical research communications. 2020 Dec. 10, v. 533, no. 3

2020

Abstract: During follicle growth, DNA methylation is gradually established, which is important for oocyte developmental competence. Due to the facts that oocytes from prepubertal individuals show reduced developmental outcomes when compared to those from sexually ... ...

Abstract	During follicle growth, DNA methylation is gradually established, which is important for oocyte developmental competence. Due to the facts that oocytes from prepubertal individuals show reduced developmental outcomes when compared to those from sexually mature individuals, and the fact that oocytes derived from in vitro follicle culture have much lower developmental competence, it is worth exploring whether prepubertal superovulation and in vitro follicle culture will cause changes in DNA methylation imprinting status in oocytes. In this study, we found that the CpG island in maternally imprinted GNAS clusters was hypermethylated in the MII-stage oocytes from sexually mature mice, but was hypomethylated in oocytes from prepuberty individuals. The GNAS clusters in the MII-stage oocytes obtained by in vitro follicle culture showed heterogeneous methylation levels, indicating different qualities of oocytes, however, three other maternally imprinted genes, Peg1, Lot1 and Impact, were all hypermethylated in the MII-stage oocytes derived from both prepubertal superovulation and in vitro follicle culture. Taken together, the findings suggest that the methylation status in GNAS clusters may potentially represent a novel epigenetic marker for oocyte quality detection.
Keywords	DNA methylation ; epigenetics ; genomic islands ; oocytes ; puberty ; research ; superovulation
Language	English
Dates of publication	2020-1210
Size	p. 586-591.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.09.055
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Article ; Online: SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing.

Liu, Wenbo / Lu, Xukun / Zhao, Zheng-Hui / Su, Ruibao / Li, Qian-Nan Li / Xue, Yue / Gao, Zheng / Sun, Si-Min Sun / Lei, Wen-Long / Li, Lei / An, Geng / Liu, Hanyan / Han, Zhiming / Ouyang, Ying-Chun / Hou, Yi / Wang, Zhen-Bo / Sun, Qing-Yuan / Liu, Jianqiao

eLife

2022 Volume 11

Abstract: Alternative splicing expands the transcriptome and proteome complexity and plays essential roles in tissue development and human diseases. However, how alternative splicing regulates spermatogenesis remains largely unknown. Here, using a germ cell- ... ...

Abstract	Alternative splicing expands the transcriptome and proteome complexity and plays essential roles in tissue development and human diseases. However, how alternative splicing regulates spermatogenesis remains largely unknown. Here, using a germ cell-specific knockout mouse model, we demonstrated that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. In the absence of SRSF10, spermatogonial stem cells can be formed, but the expansion of Promyelocytic Leukemia Zinc Finger (PLZF)-positive undifferentiated progenitors was impaired, followed by the failure of spermatogonia differentiation (marked by KIT expression) and meiosis initiation. This was further evidenced by the decreased expression of progenitor cell markers in bulk RNA-seq, and much less progenitor and differentiating spermatogonia in single-cell RNA-seq data. Notably, SRSF10 directly binds thousands of genes in isolated THY<sup>+</sup> spermatogonia, and Srsf10 depletion disturbed the alternative splicing of genes that are preferentially associated with germ cell development, cell cycle, and chromosome segregation, including Nasp, Bclaf1, Rif1, Dazl, Kit, Ret, and Sycp1. These data suggest that SRSF10 is critical for the expansion of undifferentiated progenitors by regulating alternative splicing, expanding our understanding of the mechanism underlying spermatogenesis.
MeSH term(s)	Mice ; Animals ; Male ; Humans ; Spermatogonia ; Alternative Splicing ; Spermatogenesis/genetics ; Cell Differentiation/genetics ; Meiosis ; Mice, Knockout ; Serine-Arginine Splicing Factors/genetics ; Serine-Arginine Splicing Factors/metabolism ; Repressor Proteins/metabolism ; Cell Cycle Proteins/metabolism
Chemical Substances	SRSF10 protein, human ; Serine-Arginine Splicing Factors (170974-22-8) ; Repressor Proteins ; Cell Cycle Proteins ; SRSF10 protein, mouse
Language	English
Publishing date	2022-11-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.78211
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Article: FBXO34 Regulates the G2/M Transition and Anaphase Entry in Meiotic Oocytes.

Zhao, Bing-Wang / Sun, Si-Min / Xu, Ke / Li, Yuan-Yuan / Lei, Wen-Long / Li, Li / Liu, Sai-Li / Ouyang, Ying-Chun / Sun, Qing-Yuan / Wang, Zhen-Bo

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 647103

Abstract: There are two important events in oocyte meiotic maturation, the G2/M transition and metaphase I progression. Thousands of proteins participate in regulating oocyte maturation, which highlights the importance of the ubiquitin proteasome system (UPS) in ... ...

Abstract	There are two important events in oocyte meiotic maturation, the G2/M transition and metaphase I progression. Thousands of proteins participate in regulating oocyte maturation, which highlights the importance of the ubiquitin proteasome system (UPS) in regulating protein synthesis and degradation. Skp1-Cullin-F-box (SCF) complexes, as the best characterized ubiquitin E3 ligases in the UPS, specifically recognize their substrates. F-box proteins, as the variable adaptors of SCF, can bind substrates specifically. Little is known about the functions of the F-box proteins in oocyte maturation. In this study, we found that depletion of FBXO34, an F-box protein, led to failure of oocyte meiotic resumption due to a low activity of MPF, and this phenotype could be rescued by exogenous overexpression of CCNB1. Strikingly, overexpression of FBXO34 promoted germinal vesicle breakdown (GVBD), but caused continuous activation of spindle assembly checkpoint (SAC) and MI arrest of oocytes. Here, we demonstrated that FBXO34 regulated both the G2/M transition and anaphase entry in meiotic oocytes.
Language	English
Publishing date	2021-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.647103
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Article ; Online: Specific deletion of protein phosphatase 6 catalytic subunit in Sertoli cells leads to disruption of spermatogenesis.

Lei, Wen-Long / Li, Yuan-Yuan / Meng, Tie-Gang / Ning, Yan / Sun, Si-Min / Zhang, Chun-Hui / Gui, Yaoting / Wang, Zhen-Bo / Qian, Wei-Ping / Sun, Qing-Yuan

Cell death & disease

2021 Volume 12, Issue 10, Page(s) 883

Abstract: Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the ... ...

Abstract	Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6c
MeSH term(s)	Animals ; Apoptosis ; Catalytic Domain ; Epididymis/metabolism ; Exons/genetics ; Gene Deletion ; Infertility, Male/genetics ; Integrases/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Phosphoprotein Phosphatases/deficiency ; Phosphoprotein Phosphatases/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Proteome/metabolism ; Sertoli Cells/metabolism ; Spermatogenesis ; Spermatozoa/metabolism ; Testis/metabolism ; Testis/pathology ; beta Catenin/metabolism ; Mice
Chemical Substances	Phosphoproteins ; Proteome ; beta Catenin ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; protein phosphatase 6 (EC 3.1.3.16)
Language	English
Publishing date	2021-09-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-021-04172-y
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Article ; Online: NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte-to-Embryo Transition.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2023 Volume 10, Issue 27, Page(s) e2301940

Abstract: Sperm-induced ... ...

Abstract	Sperm-induced Ca
MeSH term(s)	Humans ; Male ; Calcium/metabolism ; Homeostasis/physiology ; Oocytes/metabolism ; Semen/metabolism ; Sodium-Calcium Exchanger/genetics ; Sodium-Calcium Exchanger/metabolism ; Ubiquitination ; Animals ; Mice ; Nucleoside-Triphosphatase/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; Sodium-Calcium Exchanger ; Nucleoside-Triphosphatase (EC 3.6.1.15)
Language	English
Publishing date	2023-07-26
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202301940
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