Age-Dependent Alterations of Chromosomal Passenger Complex Members During Implantation and Decidualization in the Mouse Uterus.

Abstract

Successful embryo development, acquisition of uterine receptivity, implantation, and decidualization during the peri-implantation window are essential events that ensure a healthy pregnancy. While ovarian aging has long been considered the primary cause of age-related decline in fertility, emerging evidence demonstrates that uterine aging also compromises the ability to support pregnancy. The chromosomal passenger complex, composed of pIncenp, Aurora B, Survivin, and Borealin, is a critical regulator of cell cycle progression, particularly in chromosome condensation, mitotic spindle organization, and cytokinesis. We investigated age-associated changes in the expression and localization of those members, as well as the proliferation marker Ki-67, at implantation sites in mice during the peri-implantation period. Female mice aged 12, 20, and 26-32 weeks were used, and uterine tissues were collected on Days 5, 6, and 8 of pregnancy. Immunohistochemistry was performed to determine the localization of those proteins and Ki-67, while Western blotting was used to quantify protein expression levels. Our results revealed dynamic and age-dependent alterations in protein expression throughout pregnancy. Ki-67 expression decreased with advancing age in the luminal and glandular epithelium on Day 5, whereas pIncenp and Survivin levels were elevated in the stromal compartment of older mice. On Day 6, pIncenp, Borealin, and Survivin expression increased in the luminal epithelium of aging groups, and Aurora B expression was higher in older mice on Day 8. These findings highlight a potential role for complex dysregulation in impaired implantation/decidualization with maternal aging and may provide insight into mechanisms underlying implantation failure and recurrent pregnancy loss.