Abstract
BackgroundAnticentromere 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.MethodsWe 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.ResultsPositive 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.ConclusionsThe 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.
Highlights
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; the possible mechanism behind this phenomenon remains unknown
Mice immunized with Centromere protein (CENP)-A developed marked antiCENP-A responses After immunization with CENP-A emulsified in complete Freund’s adjuvant (CFA), mouse serum anti-CENP-A antibody was measured by indirect immunofluorescence test (IIFT) for ANA-IgG and enzyme-linked immunosorbent assay (ELISA)
All serum samples from mice immunized with CENP-A were ANA positive compared to controlled mice (Fig. 1a)
Summary
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; the possible mechanism behind this phenomenon remains unknown. In 1999, a study showed that early-stage mouse embryos cultured with purified IgG from ANA positive serum exhibited strong fluorescence and had significant growth impairment [4]. Recent retrospective clinical studies showed that disorders of oocyte maturation and early embryonic development were found in women with positive anticentromere antibody (ACA) in their peripheral blood [6, 7]. We found that embryos cultured with anti-CENP-A (centromere protein-A) antibody had significant growth impairment and/or high mortality [12]. The specific binding between ACA and CENPs is almost completely unrestricted among different species
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