The effects of follicle stimulating hormone (FSH)-induced controlled ovarian hyperstimulation and nutrition on implantation-related gene expression in caruncular tissues of non-pregnant sheep.

Disturbances at the conceptus-maternal interface can have detrimental effects on pregnancy outcome. Additionally, changes in body condition and exogenously administered gonadotropins could affect ovarian and uterine function, including cell proliferation and ovulation rates, and alter endometrial receptivity. In ruminants, endometrial caruncles maintain placental function via interaction with fetal chorionic cotyledons. Here, the effects of feeding regimens on the expression of selected genes known to be involved in uterine receptivity were investigated in the caruncles of control and FSH-superovulated ewes. Sheep were grouped according to their diet: control fed (CF), overfed (OF) or underfed (UF), and were either superovulated with FSH (SOV) or untreated (CON, naturally cycling) (n = 3-5/group). Caruncular samples for the assessment of the transcript levels of 11 target genes were collected at either the early (day 5) or mid-luteal (day 10) phases of the luteal lifespan, resulting in 12 groups of animals. The day of the estrous cycle affected the expression of ITGAV, ITGB3, FGF10 and IGFBP3 mRNA. There was lower expression of MUC1, and higher expression of FGF10, ITGB3 and FN1, on day 10 in CF_SOV animals. Compared with CF, expression of integrins (ITGB3, ITGA5 and ITGA4) was higher in OF and UF, and higher transcript levels of HGF and IGFBP3 in UF animals on day 10. Expression of ITGA5, ITGB1, -3, -5 and MUC1 was greater in OF_SOV than CF_SOV at day 10. In conclusion, it appears that imbalanced nutrition, by altering the expression of genes responsible for intercellular communication, cell adhesion, and encoding for growth factors, could affect the uterine responsiveness to exogenously applied hormonal stimulation and, likely, uterine receptivity.

Plane of nutrition and FSH-induced superovulation affect the expression of steroid hormone receptors and growth factors in caruncular tissue of non-pregnant sheep.

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.