Developmental exposure of fetal ovaries and fetal germ cells to endometriosis in an endometriosis model causes differential gene expression in the preimplantation embryos of the first-generation and second-generation embryos

Abstract

Objective: To characterize multigenerational gene expression anomalies in eight-cell stage embryos associated with developmental exposure to endometriosis.

Design: Using an endometriosis model in rats (F0 founder generation) to evaluate gene expression in F1 (fetal exposure) and F2 (fetal germ cell exposure) generation eight-cell stage embryos.

Setting: Laboratory.

Animal(s): Endometriosis model in rats (Endo) and controls (Sham).

Intervention(s): F0 Endo and Sham rats were bred; half the pregnant rats were killed on gestational day 3 to collect F1 eight-cell stage embryos and the others gestated to term (F1 females). Adult F1 females bred; F2 eight-cell embryos collected.

Main outcome measure(s): Maintenance of differential gene expression in F1 and F2 generation eight-cell embryos in endometriosis.

Result(s): Developmental exposure to endometriosis altered the gene signaling pathways, with changes found in apoptosis, the cell cycle process, the response to oxidative stress, negative regulation of molecular function, and RNA processing. The apoptotic genes Diablo, Casp3, Parp1, Cad, and Dnaja3 were increased and the Nfkbia transcripts were decreased in F1 Endo versus F1 Sham embryos. In F2 Endo versus Sham embryos, Casp3 and Cad were statistically significantly increased, and Parp1 and Nfkbia tended to be elevated.

Conclusion(s): Fetal and germ cell exposure to endometriosis alters apoptotic gene expression in first- and second-generation eight-cell stage embryos, supporting the hypothesis of multigenerational inheritance resulting from exposure to endometriosis in utero.

Keywords: Apoptosis; embryo; endometriosis; genome analysis; multigenerational.