The TRPV3 channel is a mediator of zinc influx and homeostasis in murine oocytes

Zinc (Zn²⁺) homeostasis is essential for gametogenesis and reproduction, and its deficiency causes infertility. Oocytes contain higher Zn²⁺ levels than somatic cells, and Zn²⁺ concentrations in oocytes are far higher than those of other transition metals and increase even more during maturation in preparation for fertilization. Remarkably, it is unknown what transporter(s) or channel(s) mediate Zn²⁺ influx in oocytes and whether they are expressed uniformly throughout folliculogenesis. Here, we showed that the functional expression of a member of the <u>t</u>ransient <u>r</u>eceptor <u>p</u>otential family, vanilloid 3, TRPV3, closely follows the dynamics of intracellular Zn²⁺ during oocyte maturation, raising the prospect that these events may be functionally linked. Using microfluorometry, we monitored in oocytes of <i>Trpv3</i> null females the expected rise in Zn²⁺ concentrations during maturation. Surprisingly, Zn²⁺ levels did not climb, and the overall FluoZin3 signal in <i>Trpv3</i> null eggs was lower than in control eggs. Electrophysiological recordings showed a large TRPV3 current induced by the agonist 2-APB in WT eggs supplemented with extracellular Zn²⁺ that was absent in <i>Trpv3</i> null eggs; TRPV3 showed a clear preference for Zn²⁺ over Ca²⁺. <i>Trpv3</i> null eggs displayed features associated with Zn²⁺ deficient conditions, such as lower IP₃R1 function, abnormal cortical granule distribution, and disturbed cytoskeletal organization with distinct actin nucleation disorders. Notably, <i>Trpv3</i> null eggs demonstrated undisturbed Zn²⁺ sparks. Our results suggest that TRPV3 is a pivotal member of the Zn²⁺ toolkit, mediating Zn²⁺ intake during maturation. They also indicate that distinct transporters or channels mediate Zn²⁺ influx throughout folliculogenesis.