Pitfalls in establishing mouse model of female infertility by immunization with human centromere protein

IntroductionAnticentromere autoantibodies are associated with refractory IVF/ET failure, but causality is unclear. Experimental models are needed.MethodsImmature oocytes collected from 23‐day‐old mice were matured in vitro for 18 h in a culture medium containing an anti‐human centromere protein A (CENP‐A) polyclonal antibody, and those oocytes’ maturity and chromosome/spindle structure were assessed.ResultsAntibody exposure did not affect the germinal vesicle breakdown ratio but reduced the first polar body formation ratio by 13% at the highest concentration (70.0 µg/mL). Metaphase II (MII) oocytes were stained for chromosomes/spindles and grouped into aligned/barrel‐like (AB), scattered/weakly‐stained (SW), and condensed/absent (CA). Antibody exposure decreased AB and increased SW and CA in a dose‐dependent manner. The AB/SW/CA percentages were 86/14/0, 86/14/0, 35/65/0, and 0/0/100 in the 0, 17.5, 35.0, and 70.0 µg/mL antibody groups, respectively (underlined values represent p < 0.05 compared with 0 µg/mL). Next, metaphase II oocytes were subjected to intracytoplasmic sperm injection, and the number of pronucleus/pronuclei (PN) was counted 6 h later. Antibody exposure decreased two pronuclei oocytes and increased non‐two pronuclei oocytes dose‐dependently. The percentages of 0/1/2/3 pronuclei oocytes were 43/0/57/0, 37/0/21/42, 16/28/48/8, and 91/4/4/0 in the 0, 17.5, 35.0, and 70.0 µg/mL groups, respectively.ConclusionsAnti‐CENP‐A antibody impaired a linear alignment of chromosomes at metaphase II and enhanced one or three PN formation after ICSI, which are similar to findings reported for infertile women with anticentromere autoantibodies.

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Pitfalls in establishing mouse model of female infertility by immunization with human centromere protein

Cited by 2 publications

References 42 publications

Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI

Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI

Anti‐Centromere Protein A Antibody Disrupts the Competence of Mouse Oocytes Matured In Vitro

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