Cyclical hormonal changes during an ovarian cycle may affect immune responses, which is crucial for the embryonic implantation. We aim to investigate whether the levels and activity of T, B, and NK cells change during a menstrual cycle. Twenty-two normally cycling women were enrolled and peripheral blood was drawn serially during a menstrual cycle. Intracellular cytokine expression of CD3+CD4+ and CD3+CD8+ cells, and Th1/Th2 cytokine-producing T cell ratios were determined using flow cytometric analysis. NK cell cytotoxicity was measured by flow cytometric analysis at E:T ratios of 50:1, 25:1, and 12.5:1 and also using LU at 20%. Proportions (percentage) of CD3+ (p = 0.046) and CD3+CD4+ (p = 0.002) T cells were increased in the follicular phase compared with the luteal phase. The levels of CD3−CD56+ (p = 0.010) and CD3−CD56dim (p = 0.012) NK cells and NK cytotoxicity at E:T ratio of 50:1, 25:1, and 12.5:1 and LU at 20% were significantly increased in the luteal phase compared with the follicular phase. Even though IL-10–producing CD3+CD4+ T cells were significantly lower in the midluteal phase as compared with the early follicular phase, proportions of CD19+ B cells, CD3+CD56+ NKT cells, Th1 cytokine-producing T cell subsets, and ratios of Th1/Th2 cytokine-producing T cells were not significantly changed during a menstrual cycle. We conclude that peripheral blood NK and T cell levels as well as NK cytotoxicity are changed during a menstrual cycle. Neuroendocrine regulation on immune responses is suggested during an ovarian cycle, which may be critical for embryonic implantation and pregnancy.

Ca(2+) is the universal signal for egg activation at fertilization in all sexually reproducing species. The Ca(2+) signal at fertilization is necessary for egg activation and exhibits specialized spatial and temporal dynamics. Eggs acquire the ability to produce the fertilization-specific Ca(2+) signal during oocyte maturation. However, the mechanisms regulating Ca(2+) signaling differentiation during oocyte maturation remain largely unknown. At fertilization, Xenopus eggs produce a cytoplasmic Ca(2+) (Ca(2+)(cyt)) rise that lasts for several minutes, and is required for egg activation. Here, we show that during oocyte maturation Ca(2+) transport effectors are tightly modulated. The plasma membrane Ca(2+) ATPase (PMCA) is completely internalized during maturation, and is therefore unable to extrude Ca(2+) out of the cell. Furthermore, IP(3)-dependent Ca(2+) release is required for the sustained Ca(2+)(cyt) rise in eggs, showing that Ca(2+) that is pumped into the ER leaks back out through IP(3) receptors. This apparent futile cycle allows eggs to maintain elevated cytoplasmic Ca(2+) despite the limited available Ca(2+) in intracellular stores. Therefore, Ca(2+) signaling differentiates in a highly orchestrated fashion during Xenopus oocyte maturation endowing the egg with the capacity to produce a sustained Ca(2+)(cyt) transient at fertilization, which defines the egg's competence to activate and initiate embryonic development.