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Monoallelic maternal expression of STAT5A affects embryonic survival in cattle.

Khatib H, Maltecca C, Monson RL, Schutzkus V, Rutledge JJ - BMC Genet. (2009)

Bottom Line: 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.Furthermore, the occurrence of monoallelic maternal expression of STAT5A was significantly higher in blastocysts, while paternal expression was more frequent in degenerative embryos.Our results imply that STAT5A affects embryonic survival in a manner influenced by developmental stage and allele parent of origin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dairy Science, University of Wisconsin-Madison, Madison, WI 53706, USA. hkhatib@wisc.edu

ABSTRACT

Background: Reproductive 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.

Results: We 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.

Conclusion: Our results imply that STAT5A affects embryonic survival in a manner influenced by developmental stage and allele parent of origin.

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Related in: MedlinePlus

Association analysis of 37 SNPs in selective genotyping of high and low embryo survival rate groups. SNP153137 in exon 8 of STAT5A showed the highest significant effect on early embryonic survival. Significance thresholds for the association determined via permutation with 250 iterations.
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Figure 2: Association analysis of 37 SNPs in selective genotyping of high and low embryo survival rate groups. SNP153137 in exon 8 of STAT5A showed the highest significant effect on early embryonic survival. Significance thresholds for the association determined via permutation with 250 iterations.

Mentions: First, the whole "ovary" population (n = 440) was genotyped for 14 SNPs – seven upstream of STAT5A, five within STAT5A, and two within STAT3 – and analyzed for embryonic survival and fertilization rate. The SNP153137 (G/C) in exon 8 of STAT5A (SNP12195 in our previous study) was associated with the highest significant effect (P = 0.0105) for survival rate (Figure 1A). The survival rate of embryos produced from CC dams was 12.8% higher than embryos produced from GG dams (P = 0.0027) (Table 2). Figure 1B shows that SNP153137 and SNP138337 (2.6 kb upstream of STAT5A) had the highest significant associations (P = 0.0466 and P = 0.0482, respectively) with fertilization rate. For SNP153137, the fertilization rate of oocytes obtained from CC dams was 7.7% higher than those from GG dams (P = 0.0258) (Table 2). For SNP138337, the fertilization rate of oocytes from AA dams was 5.7% lower than AG dams (P = 0.0213). Second, to fine-map the STAT5A region, we genotyped the other 23 SNPs identified in STAT5A, STAT3, and in their upstream and downstream sequences in the 100 dams with the highest embryonic survival rate and the 84 dams with the lowest survival rate. SNP153137 again showed the highest significant effect (P = 0.0014) on survival rate (Figure 2). The estimate of the effect of CC dams was 52.7% survival rate vs. 25.9% for GG dams.


Monoallelic maternal expression of STAT5A affects embryonic survival in cattle.

Khatib H, Maltecca C, Monson RL, Schutzkus V, Rutledge JJ - BMC Genet. (2009)

Association analysis of 37 SNPs in selective genotyping of high and low embryo survival rate groups. SNP153137 in exon 8 of STAT5A showed the highest significant effect on early embryonic survival. Significance thresholds for the association determined via permutation with 250 iterations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2662876&req=5

Figure 2: Association analysis of 37 SNPs in selective genotyping of high and low embryo survival rate groups. SNP153137 in exon 8 of STAT5A showed the highest significant effect on early embryonic survival. Significance thresholds for the association determined via permutation with 250 iterations.
Mentions: First, the whole "ovary" population (n = 440) was genotyped for 14 SNPs – seven upstream of STAT5A, five within STAT5A, and two within STAT3 – and analyzed for embryonic survival and fertilization rate. The SNP153137 (G/C) in exon 8 of STAT5A (SNP12195 in our previous study) was associated with the highest significant effect (P = 0.0105) for survival rate (Figure 1A). The survival rate of embryos produced from CC dams was 12.8% higher than embryos produced from GG dams (P = 0.0027) (Table 2). Figure 1B shows that SNP153137 and SNP138337 (2.6 kb upstream of STAT5A) had the highest significant associations (P = 0.0466 and P = 0.0482, respectively) with fertilization rate. For SNP153137, the fertilization rate of oocytes obtained from CC dams was 7.7% higher than those from GG dams (P = 0.0258) (Table 2). For SNP138337, the fertilization rate of oocytes from AA dams was 5.7% lower than AG dams (P = 0.0213). Second, to fine-map the STAT5A region, we genotyped the other 23 SNPs identified in STAT5A, STAT3, and in their upstream and downstream sequences in the 100 dams with the highest embryonic survival rate and the 84 dams with the lowest survival rate. SNP153137 again showed the highest significant effect (P = 0.0014) on survival rate (Figure 2). The estimate of the effect of CC dams was 52.7% survival rate vs. 25.9% for GG dams.

Bottom Line: 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.Furthermore, the occurrence of monoallelic maternal expression of STAT5A was significantly higher in blastocysts, while paternal expression was more frequent in degenerative embryos.Our results imply that STAT5A affects embryonic survival in a manner influenced by developmental stage and allele parent of origin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dairy Science, University of Wisconsin-Madison, Madison, WI 53706, USA. hkhatib@wisc.edu

ABSTRACT

Background: Reproductive 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.

Results: We 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.

Conclusion: Our results imply that STAT5A affects embryonic survival in a manner influenced by developmental stage and allele parent of origin.

Show MeSH
Related in: MedlinePlus