Dataset Information

Uterine injury during diestrus leads to embryo spacing defects and perturbations in the Cox-2 pathway in subsequent pregnancies

ABSTRACT: Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at approximately 30% of deliveries in the US that are projected to continue to climb, an understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are sorely needed. However, there are currently no animal models to date that comprehensively assess the consequences of uterine injury. Here we describe the first rodent model of uterine injury on subsequent in utero outcomes. We observed four distinct phenotypes: reduced implantation events, increased rates of resorption, embryo misspacing, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We also show that the appearance of embryo misspacing depends entirely on the phase of estrous cycle at the time of injury, leading us to identify differences in uterine wound healing as a function of estrous. Using RNA-seq, we identified perturbations in the expression of components of the COX-2 pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in our novel mouse model engenders many uterine changes, most notably perturbed expression of COX-2 pathway-related genes, that ultimately lead to numerous placental and embryonic developmental defects with parallels to human pregnancy disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE198799 | GEO | 2024/04/01

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:The aberrant gene expression in the uterine endometrium and embryo has been the major causes of pregnancy failure in cattle. Therefore, selecting cows having adequate endometrial receptivity and embryos of better developmental competence based on the gene expression could increase the number of calves produced by in each cow during its productive life time. We used endometrial and embryo biopsy technology in conjunction with the pregnancy outcome information to establish a direct link between the pre-transfer endometrial or in vivo derived embryo gene expression and pregnancy outcome after embryo transfer. Endometrial samples were collected from Simmental heifers at day 7 and 14 of the estrous cycle, one cycle prior to embryo transfer. In the next cycle, embryo biopsies consisting of 60-70% of inner cell mass and trophectoderm were transferred to the recipients at day 7 of the estrous cycle. The remaining 30-40% parts of the embryos were retained for analysis.Pregnancy diagnosis was performed at days 28 and 42 by ultrasonography and at day 56 by rectal palpation. Those heifers returned to heat at day 21 were considered as non pregnant or non receptive endometrium (NP) while those heifers ended up with successful pregnancy and calf delivery was considered as the calf delivery group or receptive endometrium (CD). Following this, the endometrial samples collected during the pre-transfer period and the embryo biopsies retained during embryo transfer were categorized based on the pregnancy outcome. Those endometrial biopsies collected at days 7 and 14 of the estrous cycle from heifers resulted in successful calf delivery were designated as CDd7 and CDd14, respectively and endometrial biopsies taken at days 7 and 14 of the estrous cycle from those subsequently resulted in no pregnancy were designated as NPd7 and NPd14, respectively. Similarly, the embryo biopsies were classified as those embryo biopsies resulted in successful calf delivery and those resulted in no pregnancy

Project description:The aberrant gene expression in the uterine endometrium and embryo has been the major causes of pregnancy failure in cattle. Therefore, selecting cows having adequate endometrial receptivity and embryos of better developmental competence based on the gene expression could increase the number of calves produced by each cow during its productive life time. We used endometrial and embryo biopsy technology in conjunction with the pregnancy outcome information to establish a direct link between the pre-transfer endometrial or in vivo derived embryo gene expression and pregnancy outcome after embryo transfer. Endometrial samples were collected from Simmental heifers at day 7 and 14 of the estrous cycle, one cycle prior to embryo transfer. In the next cycle, embryo biopsies consisting of 60-70% of inner cell mass and trophectoderm were transferred to the recipients at day 7 of the estrous cycle. The remaining 30-40% parts of the embryos were retained for analysis.Pregnancy diagnosis was performed at days 28 and 42 by ultrasonography and at day 56 by rectal palpation. Those heifers returned to heat at day 21 were considered as non pregnant or non receptive endometrium (NP) while those heifers ended up with successful pregnancy and calf delivery was considered as the calf delivery group or receptive endometrium (CD). Following this, the endometrial samples collected during the pre-transfer period and the embryo biopsies retained during embryo transfer were categorized based on the pregnancy outcome. Those endometrial biopsies collected at days 7 and 14 of the estrous cycle from heifers resulted in successful calf delivery were designated as CDd7 and CDd14, respectively and endometrial biopsies taken at days 7 and 14 of the estrous cycle from those subsequently resulted in no pregnancy were designated as NPd7 and NPd14, respectively. Similarly, the embryo biopsies were classified as those embryo biopsies resulted in successful calf delivery and those resulted in no pregnancy

Dataset Information

Uterine injury during diestrus leads to embryo spacing defects and perturbations in the Cox-2 pathway in subsequent pregnancies

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure