Abstract
Implantation is a critical step in the establishment of pregnancy and an important part of embryo-maternal contact. Uterine receptivity can be affected by changes in body condition and the maternal endocrine milieu, including those caused by the use of exogenous gonadotropins in controlled ovarian hyperstimulation to induce the development of multiple follicles. This study demonstrates the effects of FSH-mediated ovarian hyperstimulation on the caruncles of ewes under various feeding regimes. Sheep were classified into 3 categories: control fed (CF), overfed (OF), or underfed (UF). In each group, animals were superovulated with FSH or injected with a saline solution (non-treated control). Uterine caruncles were collected at the early (d 5) and mid-luteal phase (d 10) of the estrous cycle. The transcript levels of steroid hormone receptors (ESR1, ESR2, PGR) and growth factors (IGF1, IGF2, VEGFA) were investigated and their expression localized by immunohistochemical staining. As for the main findings, day of the estrous cycle affected expression of ESR1, IGF1 and IGF2, but not of ESR2, PGR and VEGFA; both feeding and superovulation had modulatory effects, with feeding (UF/OF) stimulating expression of all genes studied, and superovulation altering expression of some genes, eg IGF1, PGR and ESR1 and ESR2, in CF animals. Similarly, feeding (UF/OF) altered responsiveness to superovulation for PGR on d 5 and ESR1/ESR2 on d 5 and/or 10. Our data emphasize possible effects of dietary and/or hormonal stimuli on uterine physiology, which may affect pregnancy outcomes by disrupting uterine functionality.
Highlights
In domestic ruminants, including sheep, the endometrium contains a number of aglandular caruncles, which constitute the sites of implantation and superficial placentation during pregnancy [1]
Uterine receptivity can be affected by changes in body condition and the maternal endocrine milieu, including those caused by the use of exogenous gonadotropins in controlled ovarian hyperstimulation to induce the development of multiple follicles
We investigated the effects of FSH-mediated ovarian hyperstimulation under different feeding regimes on the expression of steroid hormone receptors (ESR1/encoding for ERα, ESR2/encoding for ERβ, and PGR) and growth factors (IGF1, IGF2, VEGFA) in caruncular tissues on days 5 and 10 of the estrous cycle, using ewes as a model
Summary
In domestic ruminants, including sheep, the endometrium contains a number of aglandular caruncles, which constitute the sites of implantation and superficial (epitheliochorial) placentation during pregnancy [1]. The attachment of the blastocyst to the uterine wall is an important event during the establishment of pregnancy It is orchestrated and controlled by complex endocrine and molecular mechanisms [3,4], in which sex steroids, intercellular communication molecules including integrins, as well as several locally produced cytokines and growth factors play major roles. The sex steroids, estrogen (E2) and progesterone (P4), are important players regulating uterine function, including cell proliferation, blood vessel formation and secretory activities [4,5,6,7]. Their signals are mediated through nuclear as well as membrane-bound receptors in the reproductive organs [8,9]. In species showing an invasive type of placentation, including the dog, the expression of IGFs is associated with the decidualization process [21,22,23]
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