Conceptus interferon gamma is essential for establishment of pregnancy in the pig

Author:

Johns Destiny N1,Lucas Caroline G1,Pfeiffer Caroline A1,Chen Paula R1,Meyer Ashley E1,Perry Shelbi D1,Spate Lee D1,Cecil Raissa F1,Fudge Melissa A1,Samuel Melissa S1,Spinka Christine M2,Liu Hongyu1,Lucy Matthew C1,Wells Kevin D1,Prather Randall S1,Spencer Thomas E1,Geisert Rodney D1

Affiliation:

1. Division of Animal Sciences, University of Missouri, Columbia, Missouri, USA

2. Division of Plant Sciences, University of Missouri, Columbia, Missouri, USA

Abstract

Abstract Establishment and maintenance of pregnancy in the pig is a complex process that relies on conceptus regulation of the maternal proinflammatory response to endometrial attachment. Following elongation, pig conceptuses secrete interferon gamma (IFNG) during attachment to the endometrial luminal epithelium. The objective here was to determine if conceptus production of IFNG is important for early development and establishment of pregnancy. CRISPR/Cas9 gene editing and somatic cell nuclear transfer technologies were used to create an IFNG loss-of-function study in pigs. Wild-type (IFNG+/+) and null (IFNG−/−) fibroblast cells were used to create embryos through somatic cell nuclear transfer. IFNG expression was not detected in IFNG−/− conceptuses on either day 15 or day 17 of pregnancy. Ablation of conceptus IFNG production resulted in the reduction of stromal CD3+ and mast cells, which localized to the site of conceptus attachment on day 15. The uteri of recipients with IFNG−/− conceptuses were inflamed, hyperemic and there was an abundance of erythrocytes in the uterine lumen associated with the degenerating conceptuses. The endometrial stromal extracellular matrix was altered in the IFNG−/− embryo pregnancies and there was an increased endometrial mRNA levels for collagen XVII (COL17A1), matrilin 1 (MATN1), secreted phosphoprotein 1 (SPP1), and cysteine-rich secretory protein 3 (CRISP3), which are involved with repair and remodeling of the extracellular matrix. These results indicate conceptus IFNG production is essential in modulating the endometrial proinflammatory response for conceptus attachment and survival in pigs.

Funder

Agriculture and Food Research Initiative Competitive

USDA National Institute of Food and Agriculture

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,General Medicine,Reproductive Medicine

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