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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P007 | DOI: 10.1530/repabs.1.P007

Oestrogen-driven changes in the bovine uterus are associated with activation of the unfolded protein response

Mohammed A Alfattah1, Paul Anthony McGettigan2, John Arthur Browne2, Khalid M Alkhodair1, Katarzyna Pluta1, Mary E Gallagher1, Colm J Reid1, Stephen D Carrington1, Alexander C O Evans2 & Jane Ann Irwin1

1UCD School of Veterinary Medicine, University College Dublin, Belfield, Ireland; 2University College Dublin, Dublin, Ireland.

The endometrium plays a central role in fertility and pregnancy. It undergoes changes in function and histological morphology over the oestrus cycle, driven by dynamic changes in progesterone and oestrogen. To understand the changes resulting from elevated oestrogen levels around oestrus, we profiled the transcriptome of the bovine uterus. Endometrial tissue was collected from synchronized beef heifers in six cohorts: i) 12 h after controlled intravaginal progesterone-releasing device (CIDR) removal; ii) 24 h after CIDR removal, iii) oestrus onset, iv) 12 h after oestrus onset, v) 48 h after oestrus onset, and vii) 7 days after oestrus onset. Gene expression levels were measured using RNA-Seq. Corresponding blood samples were submitted for hormonal analysis. The 200 genes most highly correlated with oestradiol were analysed using the Ingenuity Pathway Analysis (IPA) tool. IPA identified XBP1 (the key transcriptional regulator of the unfolded protein response (UPR)) as the top ranked upstream regulator. The UPR is usually activated in cells in response to endoplasmic reticulum stress, however it is also active in the biogenesis of the secretory machinery in exocrine cells. XBP1 exists as two isoforms XBP1(u) and XBP1(s). XBP1(s) is a potent activator of the UPR. RT-PCR indicated that XBP1(s) decreased 57% from 12 h after CIDR removal until 12 h after oestrus, then rose again in the luteal phase, indicating that XBP1(s) was induced during the progesterone-dominated phase of the cycle. Our results show that the UPR/XBP1 pathway is under hormonal control in the bovine endometrium and influences the secretory activity of the endometrium during the peri-oestrus period.