The length of the post-partum anoestrous interval affects reproductive efficiency in many tropical beef cattle herds. In this study, results from genome-wide association studies (Experiment 1: GWAS) and gene expression (Experiment 2: microarray) were combined in a systems approach to reveal genetic markers, genes and pathways underlying the physiology of post-partum anoestrus in tropically adapted cattle. The microarray study measured the expression of 13,964 genes in the hypothalamus of Brahman cows. A total of 366 genes were differentially expressed (DE) in the post-partum period, when acyclic cows were compared to cows that had resumed ovarian cycles. Associated markers (P < 0.05) from a high density GWAS pointed to 2,829 genes that were associated with post-partum anoestrous interval we found genes with changed expression in the brain that were also associated with anoestrus traits these 63 genes could have biological significance in post-partum anoestrus in cows these genes could also help select cattle with genetic potential for shorter post-partum anoestrus
The aim was to characterise gene expression in the hypothalamus of suckled and weaned postpartum beef cows. The hypothalamus was obtained at slaughter from 12 primiparous Brahman cows (Zebu, Bos indicus) at 27 and 34 days postpartum. Six cows were weaned 7 days or 14 days before slaughter. Hypothalamic regions used for gene expression were: H1 (SC-POA, APVN, anterior hypothalamic nucleus, anterior portion of the arcuate nucleus, nearby areas of the diagonal band of Broca, and medial septum); H2 (basal hypothalamus-median eminence, ventromedial hypothalamus, posterior portion of the arcuate nucleus, and anterior part of the mammillary body). Gene expression was determined using the Agilent bovine 44k DNA microarray and differential expression (DE) was ascertained by mixed model analysis. A total of 122 genes were DE in H1 and 84 genes were DE in H2; 41 DE genes were common to H1 and H2. Functional clustering of DE genes using DAVID (www.david.abcc.ncifcrf.gov) revealed DE gene clusters in H1 associated with signalling events and ion binding, and DE gene clusters in H2 associated with hormone activity and ligand-receptor interactions. Of the DE genes, ~25% were linked with oestrogen signalling. This included oestrogen receptor-α (ESR1) that showed lower DE in H2 for weaned cows. Two modulators of steroid receptor signalling, proline-rich nuclear receptor coactivator-2 (PNRC2)1 and peptidylprolyl isomerase D (PPID)2, showed altered expression. In weaned cows, expression level of PNRC2 was lower in H1 and H2, while that of PPID was decreased in H1. The overlapped hypothalamic regions H1 and H2 are known to contain GnRH neuron terminals and kisspeptin neurons. Weaning promotes the resumption of cyclic ovarian function in postpartum cows, and the similar shifts in DE of ESR1, PNRC2 and PPID provided further evidence of a role for oestradiol at the hypothalamus in regulating postpartum reproduction.
(1) Zhou D et al. 2006 Nucleic Acids Res 34:5974–86
(2) Kumar P et al. 2001 Biochem Biophys Res Commun 284:219–25
The aim was to identify hypothalamic genes associated with transition from acyclic to cyclic ovarian function in postpartum cows. Ovarian status was recorded at slaughter for primiparous Brahman cows (Zebu, Bos indicus) at 27–34 days postpartum and hypothalamic tissue was obtained at the same time. Ovaries were classified as: Ov1 (n = 4), follicles 4–5 mm; Ov2 (n = 4), follicles equal or larger 10 mm without ovulation; Ov3 (n = 4), corpus haemorrhagicum or corpus luteum. Hypothalamic regions were: H1 (SC-POA, APVN, anterior hypothalamic nucleus, anterior portion of the arcuate nucleus, nearby areas of the diagonal band of Broca, and medial septum); H2 (basal hypothalamus-median eminence, ventromedial hypothalamus, posterior portion of the arcuate nucleus, and anterior part of the mammillary body). Gene expression was determined using the Agilent bovine 44k DNA microarray and differential expression (DE) was ascertained by mixed model analysis. Functional clustering of DE genes using DAVID (www.david.abcc.ncifcrf.gov) revealed an enrichment of genes linked with synaptic transmission in H1 and H3 comparing Ov1 and Ov3. Three members of the major histocompatibility complex (MHC) class II gene family (BOLA-DQA1, BOLA-DQA2 and BOLA-DQB) showed a higher expression level in Ov2 than Ov1 in H1 and H2. BOLA-DGA2 and BOLA-DQB were downregulated in Ov3 when comparing Ov2 and Ov3. MHC family members have been associated with plasticity in the brain1. Functional clusters of genes involved in cell-cell adhesion were differentially expressed when comparing Ov1 and Ov2 (H2), and Neutropilin-2 which promotes GnRH neuronal migration2 was upregulated in Ov1. The findings provide preliminary evidence that gene expression related to cellular plasticity within the basal hypothalamus-median eminence is associated with the transition from acyclic to cyclic ovarian function in the postpartum cow.
(1) Håvik B et al. 2007 Neuroscience 148:925–36
(2) Cariboni A et al. 2007 TRENDS in Neurosciences 30:638–44
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