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[Preprint]. 2024 Oct 18:2024.10.15.618561. [Version 1] doi: 10.1101/2024.10.15.618561

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

Marika Raff, Trinity Benton, Daniel Brummond, Denali Kovach, Olivia Bunton, Ella Janky, Eyup Hakan Duran, Douglas G Scroggins, Gabrielle Gray, Sabrina Marie Scroggins
PMCID: PMC11507868  PMID: 39464145

Structured Abstract

Objective

To 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.

Design

Laboratory based experiments with female mice.

Animals

Female congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout.

Exposure

Four-week-old female CD4 RGS2 knockout (CD4 RGS2 KO ) mice and their littermate controls (CD4 RGS2 CTL ) were subjected to superovulation using pregnant mare serum gonadotropins.

Main Outcome Measures

Oocyte numbers, lymphocyte populations in the ovary and uterus, and serum estradiol and progesterone concentrations.

Result

In 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 RGS2 KO mice compared to CD4 RGS2 CTL mice. Pro-inflammatory CD4+ T helper (T H ) 1 and T H 17 cell frequencies in the ovary and uterus were unchanged, while Treg and T H 2 cell frequencies were elevated, along with increased concentrations of estradiol and progesterone in the serum of CD4 RGS2 KO mice.

Conclusion

Our 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.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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