Ca²⁺ influx and the store-operated Ca²⁺ entry pathway undergo regulation during mouse oocyte maturation

In preparation for fertilization, mammalian oocytes undergo optimization of the mechanisms that regulate calcium homeostasis. Among these changes is the increase in the content of the Ca²⁺ stores ([Ca²⁺] _ER), a process that requires Ca²⁺ influx. Nevertheless, the mechanism(s) that mediates this influx remains obscure, although is known that [Ca₂₊]_ER can regulate Ca²⁺ influx via store-operated Ca²⁺ entry (SOCE). We find that during maturation, as [Ca²⁺]_ER increases, Ca²⁺ influx decreases. We demonstrate that mouse oocytes/eggs express the two molecular components of SOCE - stromal interaction molecule 1 (Stim1) and Orai1 - and expression of human (h) Stim1 increases Ca²⁺ influx in a manner that recapitulates endogenous SOCE. We observe that the cellular distribution of hStim1 and hOrai1 during maturation undergoes sweeping changes that curtail their colocalization during the later stages of maturation. Coexpression of hStim1 and hOrai1 enhances influx throughout maturation but increases basal Ca²⁺ levels only in GV oocytes. Further, expression of a constitutive active form of hStim1 plus Orai1, which increases basal Ca²⁺ throughout maturation, disturbs resumption of meiosis. Taken together, our results demonstrate that Ca²⁺ influx and SOCE are regulated during maturation and that alteration of Ca²⁺ homeostasis undermines maturation in mouse oocytes.