The Receptive Endometrial Transcriptomic Signature Indicates an Earlier Shift from Proliferation to Metabolism at Early Diestrus in the Cow1

Abstract

This study aimed to characterize the endometrial transcriptome and functional pathways overrepresented in the endometrium of cows treated to ovulate larger (≥13 mm) versus smaller (≤12 mm) follicles. Nelore cows were presynchronized prior to receiving cloprostenol (large follicle [LF] group) or not (small follicle [SF] group), along with a progesterone (P4) device on Day (D) -10. Devices were withdrawn and cloprostenol administered 42-60 h (LF) or 30-36 h (SF) before GnRH agonist treatment (D0). Tissues were collected on D4 (experiment [Exp.] 1; n = 24) or D7 (Exp. 2; n = 60). Endometrial transcriptome was obtained by RNA-Seq, whereas proliferation and apoptosis were assessed by immunohistochemistry. Overall, LF cows developed larger follicles and corpora lutea, and produced greater amounts of estradiol (D-1, Exp. 1, SF: 0.7 ± 0.2; LF: 2.4 ± 0.2 pg/ml; D-1, Exp. 2, SF: 0.5 ± 0.1; LF: 2.3 ± 0.6 pg/ml) and P4 (D4, Exp. 1, SF: 0.8 ± 0.1; LF: 1.4 ± 0.2 ng/ml; D7, Exp. 2, SF: 2.5 ± 0.4; LF: 3.7 ± 0.4 ng/ml). Functional enrichment indicated that biosynthetic and metabolic processes were enriched in LF endometrium, whereas SF endometrium transcriptome was biased toward cell proliferation. Data also suggested reorganization of the extracellular matrix toward a proliferation-permissive phenotype in SF endometrium. LF endometrium showed an earlier onset of proliferative activity, whereas SF endometrium expressed a delayed increase in glandular epithelium proliferation. In conclusion, the periovulatory endocrine milieu regulates bovine endometrial transcriptome and seems to determine the transition from a proliferation-permissive to a biosynthetic and metabolically active endometrial phenotype, which may be associated with the preparation of an optimally receptive uterine environment.

Oviductal transcriptional profiling of a bovine fertility model by next-generation sequencing

“…Animal and reproductive management was performed as described previously [1], [2], [4]. Non-lactating, multiparous, and cyclic Nelore cows were used in this study.…”

Evidence of endometrial amino acid metabolism and transport modulation by peri-ovulatory endocrine profiles driving uterine receptivity

“…Moreover, plasmatic concentrations of P4 on D7 were also greater in cows from the LF-LCL group. More details on ovarian and endocrine responses from the LF-LCL and SF-SCL groups on D4 and D7 were published elsewhere [26, 39]. …”

“…These data can be associated with the major proliferative activity found in the LF-LCL endometrium on D4, which was related to adequate uterus conditioning for receiving the embryo [39]. This proliferative activity may also be responsible for the observation of an increase in transporter abundance without an associated increase in the concentration of the target substrate in the uterine lumen.…”

“…This phenotype is probably associated with the greater AA requirement for the subsequent stages of embryonic development (i.e., hatching and elongation). In terms of sex steroid regulation of such processes, the phenotype on D4 reflects classical actions of estradiol that include stimulation of endometrial cell proliferation, while the phenotype on D7 is associated with actions of progesterone, such as glandular secretory activity and histotroph formation to support embryonic growth [4, 39, 61–63]. A summarized view of the AA transport systems in the endometrium in association with receptivity during early diestrus is presented in Fig.…”

Impact of estradiol cypionate prior to TAI and progesterone supplementation at initial diestrus on ovarian and fertility responses in beef cows

“…For example, consistent fertility gains in TAI protocol have been achieved by extending the proestrus period [8,9] or adding exogenous E2 [5,10,11]. An adequate uterine exposure to E2 affects positively the fertilization process [12], reduces the incidence of early luteolysis [13,14], and provides an uterine environment favourable to the establishment of pregnancy [15,16]. Regarding P4 concentrations during diestrus, the relationship between P4 concentrations and fertility are generally positive [3,6,17].…”