Evidence that absence of endometrial gland secretions in uterine gland knockout ewes compromises conceptus survival and elongation

Abstract

Endometrial glands are necessary for conceptus implantation and growth. In the ovine uterine gland knockout (UGKO) model, blastocysts hatch normally but fail to survive or elongate. This peri-implantation defect in UGKO ewes may be due to the absence of endometrial glands or, alternatively, to the lack of certain epithelial adhesion molecules or the inability of the endometrium to respond to signals from the conceptus. Two studies were performed to examine these hypotheses. In study one, normal (n = 8) and UGKO (n = 12) ewes were mated at oestrus (day 0) with intact rams and their uteri were flushed 14 days after oestrus. Normal ewes (n = 4) were also flushed on 14 days after oestrus. Uterine flushes from bred normal ewes contained filamentous conceptuses (n = 7 of 8), whereas those from UGKO ewes contained no conceptus (n = 5 of 12), a growth-retarded, tubular conceptus (n = 6 of 12), or a fragmented, filamentous conceptus (n = 1 of 12). In all groups, expression of mucin 1 and integrin alpha(v), alpha(5), beta(3) and beta(5) was localized at the apical surface of the endometrial luminal epithelium with no detectable differences between normal and UGKO ewes. Uterine flushes from pregnant ewes, but not cyclic or UGKO ewes, contained abundant immunoreactive interferon tau and the cell adhesion proteins, osteopontin and glycosylation-dependent cell adhesion molecule one. In study two, UGKO ewes were fitted with uterine catheters 5 days after oestrus, infused with recombinant ovine interferon tau or control proteins from 11 to 15 days after oestrus, and underwent hysterectomy 16 days after oestrus. Expression of several interferon tau-stimulated genes (ISG17, STAT1, STAT2 and IRF-1) was increased in the endometrium from interferon tau-infused UGKO ewes. These results support the hypothesis that the defects in conceptus elongation and survival in UGKO ewes are due to the absence of endometrial glands and their secretions rather than to alterations in expression of anti-adhesive or adhesive molecules on the endometrial luminal epithelium or to the responsiveness of the endometrium to the conceptus pregnancy recognition signal.

Expression and regulation of secreted phosphoprotein 1 in the bovine corpus luteum and effects on T lymphocyte chemotaxis

“…In addition, P 4 stimulated SPP1 expression in the developing ovine uterine glandular epithelium during the peri-implantation period (Johnson et al 2000). P 4 stimulates hypertrophy and hyperplasia of the glandular epithelium and development of the uterine glands to produce numerous growth factors, in addition to SPP1, to provide hematotrophic nutrition to the conceptus (Gray et al 2002). Johnson et al (2000) suggested that P 4 upregulation of SPP1 expression within the uterus may be mediated through additional paracrine factors, such as placental lactogen.…”

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

“…Variation in proteins contained in the histotroph, which can lead to detrimental effects on conceptus growth (Gray et al 2002), may be specific to individual animals. Progesterone is one of the main regulators of the genes expressed in the endometrium that are involved in the preparation of the uterus during early pregnancy (Bazer et al 1979;Robinson et al 2008;Spencer et al 2008).…”

Uterine secretome and its modulation in rat (Rattus norvegicus)

“…Restriction of embryos to the oviduct, by ligation of the tubo-uterine junction, led to a halt in their development at the early blastocyst stage (Kirby 1962). Embryos remained unattached or became degenerated in the uterine cavity of pregnant ewes, whose uteri lacked endometrial epithelial glands and their secretions (Gray et al 2002). In humans also, infertility in some cases was found to be associated with altered levels of proteins such as leukemia inhibitory factor, proprotein convertase, and mucin-1 in the UF (Aplin et al 1996, Mikolajczyk et al 2006, Heng et al 2011.…”