Retinol-binding protein (RBP), retinol and β-carotene in the bovine uterus and plasma during the oestrous cycle and the relationship between systemic progesteroneand RBP on Day 7

Abstract

In the dairy cow, low systemic concentrations of progesterone are known to be a major factor associated with early embryo loss. Endometrial expression of the gene encoding retinol-binding protein (RBP) is sensitive to small changes in progesterone on day 7 of the oestrous cycle. The objectives of the present study were to measure RBP concentrations in bovine uterine flushings and plasma across different days of the oestrous cycle and to examine the relationship between uterine RBP and systemic concentrations of progesterone. Uterine flushings and plasma were collected from cows on days 3, 7, 11 and 15 of the oestrous cycle. Uterine RBP concentrations were five- to 15-fold higher (P < 0.001) on day 15 compared with the other days and twofold higher (P < 0.001) in the uterine horn ipsilateral to the corpus luteum on day 15. RBP concentrations were similar in flushings and plasma across days 3-11; however, day 15 RBP concentrations were six- to 15-fold higher (P < 0.001) in uterine flushings. No significant relationship was found between the concentration of systemic progesterone and RBP concentrations on day 7. Overall, the results of the present study indicate a local controlling mechanism operating at the level of the endometrium to regulate RBP secretion, most likely progesterone.

Paradoxical effect of supplementary progesterone between Day 3 and Day 7 on corpus luteum function and conceptus development in cattle

“…These findings highlight the somewhat paradoxical actions of P4. On the one hand, increased P4 concentrations stimulate conceptus elongation (Garrett et al 1988a;Satterfield et al 2006;Carter et al 2008) via well-characterised changes induced in the endometrial transcriptome (Forde et al , 2011b and associated changes in the histotroph (Costello et al 2010;Hugentobler et al 2010). Conversely, there is convincing evidence in the literature that administration of P4 early in the cycle may compromise CL function, ultimately leading to luteolysis and embryo loss (Ginther 1970;Garrett et al 1988a;Burke et al 1994;Pope et al 1995;Van Cleeff et al 1996).…”

Maternal-embryo interaction leading up to the initiation of implantation of pregnancy in cattle

“…Coordinate with this event is an alteration in the overall transcriptional profile of the endometrium (Forde et al, 2012a and allowing the switching on of genes (and their protein products) that have been shown to drive conceptus elongation in cattle or other species. This includes the increased expression and or secretion of the proteins IGFBP1 (Simmons et al, 2009), GRP, APOA1, ARSA, LCAT, NCDN, PLIN , Legumin, TIMP2 (Ledgard et al, 2009) and RBP4 (Costello et al, 2010;Mullen et al, 2012) into the uterine lumen where they are available to help promote conceptus elongation.…”

“…First, supplementation with exogenous P4 advances the down-regulation of the PGR (Okumu et al, 2010) while delaying the output of P4 from the CL, delays the down-regulation of the PGR (Forde et al, 2011a). This has consequences for the expression of genes that contribute to the histotroph; elevating P4 advances or increases the expression of genes while low P4 delays or decreases the expression of genes known to be important for histotroph composition including ANPEP, APOA1, DGAT2, FABP3, IGFBP1, IHH, LCAT, LPL, LTF, MEP1B, NID2, NMN, NPNT, NXPH3, PENK, PLIN2, PRSS23, RBP4, SCG5, SERPINA14, TINGAL1 and TFF3 (Costello et al, 2010;Forde et al, 2011a and2012a;Mullen et al, 2012). The P4 modification of the expression of these genes, and in some cases their protein products, results in a change in the capacity of the uterus to support conceptus elongation.…”

Transcriptomic Analysis of the Bovine Endometrium: What is Required to Establish Uterine Receptivity to Implantation in Cattle ?

“…Gene expression is given in italics and protein abundance is given in normal font. Data compiled from references [20,27,34,35,49,64,65,67,[74][75][76][77]. FORDE and LONERGAN 192 in both beef and dairy cattle have identified a correlation between concentrations of progesterone up to Day 7 following insemination and subsequent pregnancy rates [44,45].…”

“…One could hypothesise that this would hold true for cattle; however, there are very limited data available to test this hypothesis. The presence of both retinol and retinol binding protein (RBP) have been detected in uterine luminal fluid on Day 15 in cyclic animals [74] and the use of 2-D gel electorphoresis identified increased protein abundance of carbonic anhydrase, ezrin, heat shock protein 70, isocitrate dehydrogenase, nucleoside diphosphate kinase, peroxiredoxin 1, purine nucleoside phosphorylase, thioredoxin and triosephosphate isomerise with a coordinate decrease in cystatin E/M, legumain, RBP and tissue inhibitor of matrix metalloproteinase 2 [75]. In addition to these proteins, the concentration of 6-keto PGF1alpha, PEF2a, PGE2, PGD2 and TXB2 are higher in the uterine fluid from pregnant heifers on Day 15 and 18 compared to their cyclic counterparts [76] as well as increased concentrations of both essential and non-essential proteinogenic amino acids in the gravid uterine horn on Day 18 [77].…”