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

doi:10.1101/2024.10.15.618561

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

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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 and Sabrina Marie Scroggins

bioRxiv

Cold Spring Harbor Laboratory

10/18/2024

DOI: 10.1101/2024.10.15.618561

PMCID: PMC11507868

PMID: 39464145

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https://doi.org/10.1101/2024.10.15.618561View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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.ObjectiveTo 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.Laboratory based experiments with female mice.DesignLaboratory based experiments with female mice.Female congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout.AnimalsFemale congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout.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.ExposureFour-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.Oocyte numbers, lymphocyte populations in the ovary and uterus, and serum estradiol and progesterone concentrations.Main Outcome MeasuresOocyte numbers, lymphocyte populations in the ovary and uterus, and serum estradiol and progesterone concentrations.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.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 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.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.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.

Details

Title: Subtitle: Regulator of G-Protein Signaling 2 Knockout in CD4+ T Cells Promotes Anti-Inflammatory T Cells, Enhancing Ovulation, and Oocyte Yield
Creators: Marika Raff - University of Iowa, Obstetrics and Gynecology
Trinity Benton - College of St. Scholastica
Daniel Brummond - University of Minnesota, Duluth
Denali Kovach - University of Minnesota, Duluth
Olivia Bunton - University of Minnesota, Duluth
Ella Janky - University of Minnesota, Duluth
Eyup Hakan Duran - University of Iowa
Douglas G Scroggins - University of Minnesota, Duluth
Gabrielle Gray - University of Iowa
Sabrina Marie Scroggins - University of Minnesota, Duluth
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2024.10.15.618561
PMID: 39464145
PMCID: PMC11507868
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 10/18/2024
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984739539902771

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