Anticentromere antibody induced by immunization with centromere protein a and Freund’s complete adjuvant may interfere with mouse oocyte meiosis

Abstract Background Anticentromere antibody (ACA) is a member of the antinuclear antibody (ANA) family, and recent studies have found that ACA may be associated with oocyte maturation disorders; however, the possible mechanism behind this phenomenon remains unknown. We conducted this study to investigate whether ACA could penetrate into the living oocytes and interfere with oocyte meiosis in a mouse model. Methods We divided mice into three groups: human recombinant centromere protein-A (human CENP-A, HA) and complete Freund’s adjuvant (CFA) were used to immunize mice for the study group (HA + CFA), and mice injected with CFA (CFA group) or saline (Saline group), respectively, served as controls. After immunization, serum anti-CENP-A antibody was detected by indirect immunofluorescence assay (IIFT) and enzyme-linked immunosorbent assay (ELISA). Chromosome alignment and intracellular IgG localization in MI- and MII-stage oocytes were investigated by immunofluorescence analysis. Results Positive ACAs were successfully induced by immunization with CENP-A and CFA, and results showed that the serum level of anti-CENP-A antibody was significantly higher in the HA + CFA group compared with the control groups. There was marked increase of chromosome misalignments in MI and MII oocytes in the HA + CFA group compared to the control groups. However, no oocytes from any of the three groups showed intracellular antibody immunofluorescence. Conclusions The development and maturation of oocytes were impaired in peripheral ACA positive mice, which exhibited severe chromosomal misalignments in metaphase meiosis; however, no evidence of ACAs entering the oocytes was observed, thus the underlying mechanism needs further exploration.

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Anticentromere antibody induced by immunization with centromere protein and Freund’s complete adjuvant may interfere with mouse early-stage embryo

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00813-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Hanyan Liu ◽

Yufen Zhang ◽

Haiying Liu ◽

Qing Huang ◽

Ying Ying

Keyword(s):

Early Stage ◽

Protein A ◽

Immunofluorescence Assay ◽

Immunofluorescence Test ◽

Anticentromere Antibody ◽

Indirect Immunofluorescence Test ◽

Centromere Protein ◽

Centromere Protein A ◽

Stage Embryo ◽

Early Stage Embryo

Abstract Background Anticentromere antibody (ACA) is a member of the antinuclear antibody spectrum (ANAs) which has been speculated to be associated with subfertility. Thus, the present study aimed to investigate the induction of ACA production and its potential interference with early-stage embryos. Methods Recombinant centromere protein-A (CENP-A) or centromere protein-B (CENP-B) and complete Freund’s adjuvant (CFA) were used to immunize mice. Serum ACA level was then evaluated by using an indirect immunofluorescence test. Immunofluorescence assay was performed to detect IgG in follicles in ovarian tissues and early-stage embryos. Results Following treatment, serum positive ACA was observed in mice treated with CENP and CFA. Furthermore, IgG were detected in follicular fluid and early-stage embryos from mice treated with CENP and CFA. Conclusions This study preliminarily indicated that ACA induced by CENP and CFA may penetrate into the living embryos of early-stage in mice.

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Centromere assembly and non-random sister chromatid segregation in stem cells

Essays in Biochemistry ◽

10.1042/ebc20190066 ◽

2020 ◽

Vol 64 (2) ◽

pp. 223-232 ◽

Cited By ~ 1

Author(s):

Ben L. Carty ◽

Elaine M. Dunleavy

Keyword(s):

Stem Cells ◽

Cell Division ◽

Cell Fate ◽

Sister Chromatid ◽

Asymmetric Cell Division ◽

Protein A ◽

Germline Stem Cells ◽

Sister Chromatids ◽

Centromere Protein A ◽

Oocyte Meiosis

Abstract Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.

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998 CENTROMERE PROTEIN A IS OVEREXPRESSED IN HEPATOCELLULAR CARCINOMA AND INVOLVED IN CELL CYCLE REGULATION

Journal of Hepatology ◽

10.1016/s0168-8278(10)60999-3 ◽

2010 ◽

Vol 52 ◽

pp. S385

Author(s):

Y. Li ◽

Z. Zhu ◽

S. Zhang ◽

D. Yu ◽

H. Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Cell Cycle Regulation ◽

Protein A ◽

Centromere Protein ◽

Centromere Protein A ◽

Cycle Regulation

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Anti-centromere protein A antibodies in systemic sclerosis: Significance and origin

Autoimmunity Reviews ◽

10.1016/j.autrev.2015.10.001 ◽

2016 ◽

Vol 15 (1) ◽

pp. 102-109 ◽

Cited By ~ 11

Author(s):

Federico Perosa ◽

Marcella Prete ◽

Giuseppe Di Lernia ◽

Carmela Ostuni ◽

Elvira Favoino ◽

...

Keyword(s):

Systemic Sclerosis ◽

Protein A ◽

Centromere Protein ◽

Centromere Protein A

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Functional Complementation of Human Centromere Protein A (CENP-A) by Cse4p from Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.24.15.6620-6630.2004 ◽

2004 ◽

Vol 24 (15) ◽

pp. 6620-6630 ◽

Cited By ~ 93

Author(s):

Gerhard Wieland ◽

Sandra Orthaus ◽

Sabine Ohndorf ◽

Stephan Diekmann ◽

Peter Hemmerich

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Budding Yeast ◽

Protein A ◽

Human Cells ◽

Cycle Arrest ◽

Centromere Protein ◽

Centromere Protein A

ABSTRACT We have employed a novel in vivo approach to study the structure and function of the eukaryotic kinetochore multiprotein complex. RNA interference (RNAi) was used to block the synthesis of centromere protein A (CENP-A) and Clip-170 in human cells. By coexpression, homologous kinetochore proteins from Saccharomyces cerevisiae were then tested for the ability to complement the RNAi-induced phenotypes. Cse4p, the budding yeast CENP-A homolog, was specifically incorporated into kinetochore nucleosomes and was able to complement RNAi-induced cell cycle arrest in CENP-A-depleted human cells. Thus, Cse4p can structurally and functionally substitute for CENP-A, strongly suggesting that the basic features of centromeric chromatin are conserved between yeast and mammals. Bik1p, the budding yeast homolog of human CLIP-170, also specifically localized to kinetochores during mitosis, but Bik1p did not rescue CLIP-170 depletion-induced cell cycle arrest. Generally, the newly developed in vivo complementation assay provides a powerful new tool for studying the function and evolutionary conservation of multiprotein complexes from yeast to humans.

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