Exploration of Global Gene Expression Changes During the Estrous Cycle in Equine Endometrium1

Abstract

The equine endometrium exhibits characteristic morphological and functional changes during the estrous cycle controlled by the interplay of progesterone and estradiol. A microarray analysis of endometrial tissue samples derived from five time points of the estrous cycle (Day [D] 0, D3, D8, D12, and D16) was performed to study the dynamics of equine endometrial gene expression. Statistical analysis revealed 4996 genes differentially expressed during the estrous cycle. Clustering of similar expression profiles was performed to find groups of coregulated genes. This revealed eight major profiles: highest mRNA concentrations on D0, from D0 to D3, on D3, from D3 to D8, on D8, from D8 to D12, from D12 to D16, and on D16. Bioinformatics analysis revealed distinct molecular functions and biological processes for the individual expression profiles characterizing the different phases of the estrous cycle (e.g., extracellular matrix and inflammatory response during the estrus phase, cell division and cell cycle during early luteal phase, and endoplasmic reticulum, protein transport, and lipid metabolism in the luteal phase). A comparison to dynamic gene expression changes in bovine endometrium identified common and species-specific gene regulations in cyclic endometrium. Analysis of expression changes during the estrous cycle for genes previously found to be differentially expressed on D12 of pregnancy provided new evidence for possible regulation of these genes. This study provides new insights regarding global changes of equine endometrial gene expression as molecular reflections of physiological changes in the cyclic equine endometrium with regard to the crucial role of this tissue for successful reproduction.

Proteomes of the Female Genital Tract During the Oestrous Cycle

“…The comparison of previously published transcriptomes (14,20,21,33,34) and tissue proteomes (23,25) in other models with the sheep luminal proteomes from this study provided some information about the possible secretory origin of many proteins, suggesting that the regulation of the protein abundance along the cycle may be associated to a significant extent with endocrine control of the expression of several genes.…”

“…The regulation of the uterine transcriptome during the preimplantation phase has been intensively studied in several species (sheep (73), bovine (74,75), horse (21,76), and pig (77)(78)(79)) and the proteome of uterine fluid during the early stages of pregnancy was analyzed in cattle and sheep (80 -82). Several proteins we found more abundant in the uterine luminal fluid during the luteal phase were also described as uterine markers of early pregnancy with an increased production in the presence of an embryo.…”

“…But few studies investigated the uterus activity along the cycle, including at oestrous when the uterus is putatively interacting with spermatozoa. The expression of the transcriptome of the endometrium along the oestrous cycle was investigated in bovine (20), equine (21) and mouse (22). In human, the proteome of the uterus along the menstrual cycle was studied either on endometrium epithelium (23)(24)(25)(26) or on uterine fluid (27)(28)(29).…”

Expression of receptors for ovarian steroids and prostaglandin E2 in the endometrium and myometrium of mares during estrus, diestrus and early pregnancy

“…Increased endometrial transcripts for ESR1 during estrus and decreased during late diestrus have been reported in ruminants (Kimmins and MacLaren, 2001;Martin et al, 2008;Spencer and Bazer, 2002) and in the horse (Gebhardt et al, 2012;Hartt et al, 2005). In E.S.M.…”

Dual effect of hormones on mare reproductive physiology and dysfunction

“…The main ovarian steroids that rule reproductive physiological events in the mare are estrogens (E2) synthetized by ovarian follicles in the follicular phase, and progesterone (P4) produced by the corpus luteum (CL) in the luteal phase. In fact, in the mare endometrium, during estrus, high levels of ovarian steroid receptors, such as ER , ER and PR mRNA and protein have been detected in luminal and glandular epithelia, as well as in stromal cells (Watson et al 1992, Gebhardt et al 2012, Silva et al 2014. In addition, a positive correlation between mRNA expression of ER and ER has been reported in mare endometrium (Honnens et al 2011).…”