title: The Receptive Endometrial Transcriptomic Signature Indicates an Earlier Shift from Proliferation to Metabolism at Early Diestrus in the Cow.
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 Devices were withdrawn and cloprostenol administered 42-60 h (LF) or 30-36 h (SF) before GnRH agonist treatment (D0).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.
authors.affiliation: Universidade Federal do Pampa, Curso de Medicina Veterinária, Uruguaiana, Rio Grande do Sul, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Mesquita
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: Ramos
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Pugliesi
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil Universidade de São Paulo, Escola Superior de Agricultura "Luiz de Queiroz", Departamento de Zootecnia, Piracicaba, São Paulo, Brazil.
authors.forename: S C S
authors.initials: SC
authors.lastname: Andrade
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Van Hoeck
authors.affiliation: University of Antwerp, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Wilrijk, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Langbeen
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil.
authors.forename: M L
authors.initials: ML
authors.lastname: Oliveira
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Gonella-Diaza
authors.affiliation: Universidade de São Paulo, Escola Superior de Agricultura "Luiz de Queiroz", Departamento de Zootecnia, Piracicaba, São Paulo, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Gasparin
authors.affiliation: Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Pirassununga, São Paulo, Brazil.
authors.forename: H
authors.initials: H
authors.lastname: Fukumasu
authors.affiliation: Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Pirassununga, São Paulo, Brazil.
authors.forename: L H
authors.initials: LH
authors.lastname: Pulz
authors.affiliation: Universidade Estadual Paulista "Júlio de Mesquita Filho", Campus Experimental de Dracena, Dracena, São Paulo, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Membrive
authors.affiliation: Universidade de São Paulo, Escola Superior de Agricultura "Luiz de Queiroz", Departamento de Zootecnia, Piracicaba, São Paulo, Brazil.
authors.forename: L L
authors.initials: LL
authors.lastname: Coutinho
authors.affiliation: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Reprodução Animal, Pirassununga, São Paulo, Brazil binelli@usp.br.
authors.forename: M
authors.initials: M
authors.lastname: Binelli
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000502:physiology; D002417:Cattle; D049109:Cell Proliferation; D003008:Cloprostenol / Q000494:pharmacology; D019295:Computational Biology; D004031:Diestrus / Q000502:physiology*; D004717:Endometrium / Q000254:growth & development / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D008186:Luteolytic Agents / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects / Q000648:ultrastructure; D011247:Pregnancy; D059467:Transcriptome / Q000235:genetics*
chemical_list: D008186:Luteolytic Agents; D003008:Cloprostenol; D053148:Caspase 3
keywords: camel); endometrium; fertility; genomics; gonadal steroids; llama; ruminants (cows; sheep