BCAS2 is involved in alternative splicing and mouse oocyte development

Zhang, Jiaqi; Liu, Wenbo; Li, Guangyue; Xu, Chengpeng; Nie, Xiaoqing; Qin, Dandan; Wang, Qizhi; Lu, Xukun; Liu, Jianqiao; Li, Lei

doi:10.1096/fj.202101279r

Cited by 7 publications

(8 citation statements)

References 56 publications

(156 reference statements)

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“…To acquire a sufficient number of oocytes, 7.5 IU of pregnant mare’s serum gonadotropin (PMSG, Ningbo Pharmacy Factory, China) was injected into a 6-week-old female, and the cumulus-oocyte-complexes (COCs) were obtained after 44–46 h by puncturing ovarian antral follicles as described in a previous study [ 50 ]. Finally, GV-stage COCs were cultured in an M16 medium (Sigma Chemical Co., St. Louis, MO, USA) in a humidified atmosphere of 5% CO 2 at 37.5 °C for 5 and 12 h to count GVBD- and MII-stage oocytes, respectively.…”

Section: Methodsmentioning

confidence: 99%

Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes

Xiong

Zhang

Yang

et al. 2022

IJMS

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The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of Kdm2a, the zona pellucida 3-Cre (Zp3-Cre)/LoxP system was used to generate an oocyte Kdm2a conditional knockout (Zp3-Cre; Kdm2aflox/flox, termed Kdm2a cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult Kdm2a cKO female mice mating with wildtype males than that of the control (Kdm2aflox/flox) group. To analyze the potential causes, the ovaries of Kdm2a cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between Kdm2a cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout Kdm2a, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of Kdm2a cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of Kdm2a, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in Kdm2a cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout Kdm2a gene led to female subfertility, suggesting the crucial role of Kdm2a in epigenetic modification and follicular and oocyte development.

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Section: Methodsmentioning

confidence: 99%

Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes

Xiong

Zhang

Yang

et al. 2022

IJMS

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“…According to previous reports, BCAS2 is involved in mRNA splicing through the PRP19 complex [ 14 , 26 ]. To further explore how BCAS2 participates in RNA processing in granulosa cells, we performed Co-IP and revealed that BCAS2 interacts with PRP19 complex core proteins (Fig.…”

Section: Bcas2 Regulated the Cellular Senescence Of Functional Genesmentioning

confidence: 99%

“…Specific disruption of Bcas2 in male germ cells affected mouse spermatogenesis and male fertility by regulating AS, which decreases the full-length formation of deleted azoospermia-like ( Dazl ) [ 25 ]. Vasa-Cre mediated deletion of Bcas2 caused poor oocyte quality, abnormal oogenesis, and follicular development, possibly by regulating the AS of functional genes through the PRP19 complex [ 26 ]. Maternal depletion of Bcas2 by Zp3-Cre mice destroyed the genomic integrity of early embryos and resulted in female infertility [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

BCAS2 regulates granulosa cell survival by participating in mRNA alternative splicing

et al. 2023

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Background Granulosa cell proliferation and differentiation are essential for follicle development. Breast cancer amplified sequence 2 (BCAS2) is necessary for spermatogenesis, oocyte development, and maintaining the genome integrity of early embryos in mice. However, the function of BCAS2 in granulosa cells is still unknown. Results We show that conditional disruption of Bcas2 in granulosa cells caused follicle development failure; the ratio of the positive cells of the cell proliferation markers PCNA and Ki67 were unchanged in granulosa cells. Specific deletion of Bcas2 caused a decrease in the BrdU-positive cell ratio, cell cycle arrest, DNA damage, and an increase in apoptosis in granulosa cells, and RPA1 was abnormally stained in granulosa cells. RNA-seq results revealed that knockout of Bcas2 results in unusual expression of cellular senescence genes. BCAS2 participated in the PRP19 complex to mediate alternative splicing (AS) of E2f3 and Flt3l mRNA to inhibit the cell cycle. Knockout of Bcas2 resulted in a significant decrease in the ratio of BrdU-positive cells in the human granulosa-like tumour (KGN) cell line. Conclusions Our results suggest that BCAS2 may influence the proliferation and survival of granulosa cells through regulating pre-mRNA splicing of E2f3 and Flt3l by forming the splicing complex with CDC5L and PRP19.

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“…Previous studies have reported that loss of BCAS2 in oocytes leads to poor oocyte quality, abnormal oogenesis, and disrupted follicular development. Further studies have found that the destruction of BCAS2 leads to the degradation of the PRP19 core protein in mouse oocytes, which affects AS 21 . BCAS2 is essential for female mouse fertility as it maintains genome integrity in early embryos via modulation of DNA repair modulation 22 .…”

Section: Introductionmentioning

confidence: 99%

“…Further studies have found that the destruction of BCAS2 leads to the degradation of the PRP19 core protein in mouse oocytes, which affects AS. 21 BCAS2 is essential for female mouse fertility as it maintains genome integrity in early embryos via modulation of DNA repair modulation. 22 However, the role of BCAS2 in oocyte meiosis has not been reported.…”

Section: Introductionmentioning

confidence: 99%

BCAS2 regulates oocyte meiotic prophase I by participating in mRNA alternative splicing

Yao,

Wang,

et al. 2023

The FASEB Journal

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Oocyte meiotic prophase I (MI) is an important event in female reproduction. Breast cancer amplified sequence 2 (BCAS2) is a component of the spliceosome. Previous reports have shown that BCAS2 is critical in male germ cell meiosis, oocyte development, and early embryo genome integrity. However, the role of BCAS2 in oocyte meiosis has not been reported. We used Stra8‐GFPCre mice to knock out Bcas2 in oocytes during the pachytene phase. The results of fertility tests showed that Bcas2 conditional knockout (cKO) in oocytes results in infertility in female mice. Morphological analysis showed that the number of primordial follicles in the ovaries of 2‐month‐old (M) mice was significantly reduced and that follicle development was blocked. Further analysis showed that the number of primordial follicles decreased and that follicle development was slowed in 7‐day postpartum (dpp) ovaries. Moreover, primordial follicles undergo apoptosis, and DNA damage cannot be repaired in primary follicle oocytes. Meiosis was abnormal; some oocytes could not reach the diplotene stage, and more oocytes could not develop to the dictyotene stage. Alternative splicing (AS) analysis revealed abnormal AS of deleted in azoospermia like (Dazl) and diaphanous related formin 2 (Diaph2) oogenesis‐related genes in cKO mouse ovaries, and the process of AS was involved by CDC5L and PRP19.

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BCAS2 is involved in alternative splicing and mouse oocyte development

Cited by 7 publications

References 56 publications

Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes

Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes

BCAS2 regulates granulosa cell survival by participating in mRNA alternative splicing

BCAS2 regulates oocyte meiotic prophase I by participating in mRNA alternative splicing

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