Regulator of G-Protein Signaling 2 Knockout in CD4+ T Cells Promotes Anti-Inflammatory T Cells, Enhancing Ovulation, and Oocyte Yield

Abstract

Structured AbstractO_ST_ABSObjectiveC_ST_ABSTo determine the downstream effects on ovarian function and immune cell differentiation in the ovary and uterus using a model in which RGS2 was knocked out specifically in CD4+ T cells. DesignLaboratory based experiments with female mice. AnimalsFemale congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout. ExposureFour-week-old female CD4 RGS2 knockout (CD4 RGS2KO) mice and their littermate controls (CD4 RGS2CTL) were subjected to superovulation using pregnant mare serum gonadotropins. Main Outcome MeasuresOocyte numbers, lymphocyte populations in the ovary and uterus, and serum estradiol and progesterone concentrations. ResultIn non-congenic (mixed strain) mice, CD4 RGS2 knockout (KO) promoted higher oocyte ovulation and increased uterine total leukocyte numbers. Similarly, congenic (fully backcrossed strain) mice showed higher oocyte numbers and increased uterine total leukocytes in the CD4 RGS2KO mice compared to CD4 RGS2CTL mice. Pro-inflammatory CD4+ T helper (TH) 1 and TH17 cell frequencies in the ovary and uterus were unchanged, while Treg and TH2 cell frequencies were elevated, along with increased concentrations of estradiol and progesterone in the serum of CD4 RGS2KO mice. ConclusionOur study highlights the important role of RGS2 in CD4+ T cells within the context of reproduction. The dysregulation of immune responses due to RGS2 knockout in CD4+ T cells appears to enhance oocyte production. Further research is warranted to elucidate the precise mechanisms by which RGS2 influences reproductive outcomes, including its impact on fecundability, endometrial receptivity, and successful implantation.