Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows

Abstract

BackgroundRepeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis.MethodsThe caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium.ResultsMicroarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins were localized in luminal and glandular epithelial cells and stroma of the endometrium.ConclusionThe present study showed that endometrial gene expression profiles are different between RB and non-RB cows. The identified candidate endometrial genes and functions in each endometrial compartment may contribute to bovine reproductive performance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-017-0237-6) contains supplementary material, which is available to authorized users.

Mating to Intact, but Not Vasectomized, Males Elicits Changes in the Endometrial Transcriptome: Insights From the Bovine Model

“…Additionally, serine protease 2 (PRSS2), which also participates in tissue remodeling by type 1 collagen degradation, was down-regulated by exposure to SP and sperm at mating. Interestingly, this gene is up-regulated in the endometrium of repeat breeder cows, those that are cycling normally and without clinical abnormalities but that fail to conceive after at least two successive inseminations (Hayashi et al, 2017). Mating to an intact bull also affected genes involved in cell proliferation, such as CCAAT enhancer binding protein delta (CEBPD), which was found to be down-regulated in the endometrium of heifers mated with intact bulls.…”

“…Moreover, expression of some genes (PLA2G10, CX3CL1, C4BPA, PRSS2, BLA-DQB, and CEBPD) found differentially expressed in RNA-sequencing analysis of endometrium samples was also interrogated. The selection of these genes as interesting targets was based on literature searching (Wedel and Lömsziegler-Heitbrock, 1995;Blom et al, 2004;Hannan et al, 2004;Tapia et al, 2008;Hayashi et al, 2017;Neupane et al, 2017;Pinto De Melo et al, 2017;Tríbulo et al, 2018) and GO term analysis.…”

Adhesion molecules in gamete transport, fertilization, early embryonic development, and implantation—role in establishing a pregnancy in cattle: A review

“…For example, SNPs in the l ‐selectin gene cluster were associated with fertility and longevity in Holstein Friesian cows (X. Chen et al, 2017). In a recent study in female Brahman and Nellore cattle (de Melo, Fortes, Hayes, de Albuquerque, & Carvalheiro, 2019), SNPs associated with fertility were linked with blastocyst development (genes GCGN , ATF6B ; Gad et al, 2011), embryonic development (genes NF1B , NAPA , ZPR1 , TAF8 , HEX1M1 , HEX1M2 ; Mamo et al, 2011; Al Naib, Mamo, & Lonergan, 2012), uterine function (genes C11H2orf49 , CCND3 ; Hayashi et al, 2017), and general cell proliferation and morphogenesis (gene CHSY1 ; Becker‐Santos, Lonergan, Gronostajski, & Lam, 2017). While the study of de Melo et al (2019) did not specifically address adhesion molecules it did illustrates the importance of early reproductive events in determining reproductive outcome.…”

Across‐breed validation study confirms and identifies new loci associated with sexual precocity in Brahman and Nellore cattle

“…Some of the genes presented in Table (SNP validated for SC) were related to reproductive events. On BTA11, the gene C11H2orf49 , homologue of C2orf49 , was down‐regulated in uterus of repeat breeder cows compared with non‐repeat breeder cows (Hayashi et al, ). On BTA12, the gene NEK3 is associated with prolactin receptor in humans (Miller, DeMaria, Freier, Riegel, & Clevenger, ).…”