Bovine FRAS1: mRNA Expression Profile, Genetic Variations, and Significant Correlations with Ovarian Morphological Traits, Mature Follicle, and Corpus Luteum.

Abstract

The amelioration of bovine fertility caused by a multi-factorial problem has always been a hot topic, among which the detection of available target genes is the most crucial. It was hypothesized that the Fraser extracellular matrix complex subunit 1 (FRAS1) gene detected by GWAS is involved in physiological activities such as ovarian development. Herein, unilateral ovaries from 2111 cows were used to examine the mRNA expression profile and polymorphisms of bovine FRAS1 and their associations with fertility-related characteristics. Firstly, it was confirmed that FRAS1 gene transcripts are expressed in various bovine tissues. Then, among five potential insertion-deletion (indel) loci, the 20 bp (named P3-D20-bp) and 15 bp (P4-D15-bp) deletion mutations were confirmed to be polymorphic with linkage equilibrium. Secondly, the P3-D20-bp polymorphism was significantly associated with ovarian weight and corpus luteum diameter in the metaestrus phase and ovarian length in the dioestrum stage. Additionally, both ovarian length and mature follicle diameter in metaestrus are significantly correlated with different genotypes of P4-D15-bp. Thirdly, the transcriptional expression of the FRAS1 gene in groups with a minimum value of ovarian weight or volume was significantly higher than the expression in groups with a maximum value. Instead of that, the more corpus luteum and mature follicles there are, the higher the transcription expression of the FRAS1 gene is. Furthermore, FRAS1 expression in cows with a heterozygous genotype (ID) of P3-D20-bp was significantly higher than others. Eventually, P3-D20-bp deletion could disturb the binding efficiency of WT1-I and Sox2 to FRAS1 sequence according to binding prediction, indicating that mutation may affect gene expression and traits by influencing the binding of transcription factors. Overall, the polymorphisms of P3-D20-bp and P4-D15-bp of the bovine FRAS1 gene significantly correlated to follicle or ovarian traits that could be applied in optimizing female fertility in cow MAS breeding programs.