Abstract

BackgroundReproductive disorders and infertility are surprisingly common in the human population as well as in other species. The decrease in fertility is a major cause of cow culling and economic loss in the dairy herd. The conception rate has been declining for the past 30–50 years. Conception rate is the product of fertilization and embryonic survival rates. In a previous study, we have identified associations of several single nucleotide polymorphisms (SNPs) in the signal transducer and activator 5A (STAT5A) with fertilization and survival rates in an in vitro experimental system. The objectives of this study are to fine map the STAT5A region in a search for causative mutations and to investigate the parent of origin expression of this gene.ResultsWe have performed a total of 5,222 fertilizations and produced a total of 3,696 in vitro fertilized embryos using gametes from 440 cows and eight bulls. A total of 37 SNPs were developed in a 63.4-kb region of genomic sequence that includes STAT5A, STAT3, and upstream and downstream sequences of these genes. SNP153137 (G/C) in exon 8 of STAT5A was associated with a significant variability in embryonic survival and fertilization rate compared to all other examined SNPs. Expression analysis revealed that STAT5A is primarily monoallelically expressed in early embryonic stages but biallelically expressed in later fetal stages. Furthermore, the occurrence of monoallelic maternal expression of STAT5A was significantly higher in blastocysts, while paternal expression was more frequent in degenerative embryos.ConclusionOur results imply that STAT5A affects embryonic survival in a manner influenced by developmental stage and allele parent of origin.

Highlights

  • Reproductive disorders and infertility are surprisingly common in the human population as well as in other species

  • In a previous study, using the candidate pathway approach, signal transducer and activator 5A (STAT5A) was chosen as a candidate gene for early embryonic survival because of its roles in embryonic development and in the signal transduction pathway of interferon-tau (IFNT), which has a key role in the initiation and maintenance of pregnancy in ruminants [6]

  • We identified 12 single nucleotide polymorphisms (SNPs) and found that some of them were associated with fertilization and survival rates in a population of 1,500 in vitro fertilized (IVF) embryos produced from three sires and 160 dams [7]

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Summary

Introduction

Reproductive disorders and infertility are surprisingly common in the human population as well as in other species. We have identified associations of several single nucleotide polymorphisms (SNPs) in the signal transducer and activator 5A (STAT5A) with fertilization and survival rates in an in vitro experimental system. We identified 12 single nucleotide polymorphisms (SNPs) and found that some of them were associated with fertilization and survival rates in a population of 1,500 in vitro fertilized (IVF) embryos produced from three sires and 160 dams [7]. It was not clear whether the observed effects were related to SNPs in STAT5A or to other SNPs in linkage disequilibrium with a causative mutation in the STAT5A region. To better understand the mechanisms by which STAT5A affects fertilization and embryo survival, the second objective of this study was to investigate the expression patterns of this gene in blastocysts and degenerative embryos and to analyze its sequence characteristics

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