Actions of progesterone on uterine immunosuppression and endometrial gland development in the uterine gland knockout (UGKO) ewe

Abstract

In ewes, the uterine gland knockout (UGKO) phenotype is caused by neonatal exposure to norgestomet to arrest uterine gland development and produce an adult which has a uterus characterized by the lack of endometrial glands. Since endometrial glands in the sheep produce the lymphocyte-inhibitory protein, ovine uterine serpin (OvUS), an experiment was conducted with ewes of the UGKO phenotype to evaluate whether the inhibitory actions of progesterone on tissue rejection responses in utero are dependent upon the presence of endometrial glands. Control and UGKO ewes were ovariectomized and subsequently treated with either 100 mg/day progesterone or corn oil vehicle for 30 days. An autograft and allograft of skin were then placed in each uterine lumen and treatments were continued for an additional 30 days before grafts were examined for survival. All autografts survived and had a healthy appearance after histological analysis. Allografts were generally rejected in ewes treated with vehicle but were present for hormone-treated ewes, regardless of uterine phenotype. Analysis of the histoarchitecture and protein synthetic capacity of the uterus revealed that progesterone induced differentiation of endometrial glands and synthesis and secretion of OvUS in UGKO ewes. The UGKO ewes had reduced density of CD45R+ lymphocytes in the endometrial epithelium and there was a tendency for progesterone to reduce this effect in luminal epithelium. Taken together, results confirm the actions of progesterone to inhibit graft rejection response in utero. Responses of UGKO ewes to progesterone indicate that the hormone can induce de novo development and differentiation of endometrial glands, at least when skin grafts are in the uterus.

ACP5 (Uteroferrin): Phylogeny of an Ancient and Conserved Gene Expressed in the Endometrium of Mammals1

“…Pregnant endometrium was obtained from cow (Bos taurus; Day 100), mare (Equus cabalus; Day 59), bitch (Canis lupus familiaris; Day 60), rhesus monkey (Days 36 and 37), and rat (Day 10.5). Also, uteroplacental tissue from a pregnant mouse (Day 14) as well as intercaruncular endometrium from an ovariectomized ewe (Ovis aries) treated with 100 mg of progesterone for 60 days [20] were also included in the present study. Quality and concentration of the total RNA collected were determined spectrophotometrically.…”

“…Aliquants of purified pig ACP5 [22] and uterine flushing from an ovariectomized ewe treated with corn oil (the vehicle for progesterone) for 60 days were included as positive and negative controls, respectively. Western blot analysis was performed as described elsewhere [20] with minor modifications. Briefly, the blocking and incubation buffer was TBS-T (10 mM Tris [pH 7.6], 0.9% [w/v] NaCl, and 0.3% [v/v] Tween-20) that contained 5% (w/v) nonfat dry milk.…”

Expression profiles of interferon‐stimulated gene 15 and prostaglandin synthases in the ovine lymph nodes during early pregnancy

“…It has been reported that the interferon‐stimulated gene 15 kDa protein (ISG15) is expressed in the uterus (Johnson et al, ), CL, blood cells (Oliveira et al, ), and bone marrow (Yang, Liu et al, ) during early pregnancy in sheep, which is induced by the IFNT through an endocrine manner in sheep (Bott et al, ). Furthermore, the IFNT modifies the maternal immune system to adapt to the presence of a fetal allograft in sheep and cattle (Padua, Tekin, Spencer, & Hansen, ; Skopets, Li, Thatcher, Roberts, & Hansen, ; Walker et al, ). Lymph nodes spread throughout the lymphatic system and are the sites where the immune reaction or suppression takes place (Buettner & Bode, ).…”

Immunological mechanisms to establish embryo tolerance in early bovine pregnancy

“…A central mechanism to protect the conceptus before implantation is attributed to the immunesuppressive actions of progesterone (P 4 ). For example, P 4 delays rejection of an allograft transplanted in the uterus of ovariectomised P 4 -treated ewes (Padua et al 2005).…”