Progesterone and Placental Hormone Actions on the Uterus: Insights from Domestic Animals1

Abstract

Progesterone is unequivocally required for maternal support of conceptus (embryo/fetus and associated extraembryonic membranes) survival and development. In cyclic sheep, progesterone is paradoxically involved in suppressing and then initiating development of the endometrial luteolytic mechanism. In cyclic and pregnant sheep, progesterone negatively autoregulates progesterone receptor (PR) gene expression in the endometrial luminal (LE) and superficial glandular epithelium (GE). In cyclic sheep, PR loss is closely followed by increases in epithelial estrogen receptor (ERalpha) and then oxytocin receptor (OTR), allowing oxytocin to induce uterine release of luteolytic prostaglandin F2alpha pulses. In pregnant sheep, the conceptus produces interferon tau (IFNtau) that acts on the endometrium to inhibit transcription of the ERalpha gene and thus development of the endometrial luteolytic mechanism. After Day 13 of pregnancy, the endometrial epithelia do not express the PR, whereas the stroma and myometrium remain PR positive. The absence of PR in the endometrial GE is required for onset of differentiated function of the glands during pregnancy. The sequential, overlapping actions of progesterone, IFNtau, placental lactogen (PL), and growth hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function during gestation. In pigs, estrogen, the pregnancy-recognition signal, increases fibroblast growth factor 7 (FGF-7) expression in the endometrial LE that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the receptor for FGF-7. Strategic manipulation of these physiological mechanisms may offer therapeutic schemes to improve uterine capacity, conceptus survival, and reproductive health of domestic animals and humans.

Correlation of Oxytocin (OTR) and Estrogen Receptor (ER) mRNA in the Canine Placenta with the Detected Circulating Levels of Oxytocin and Estrogen during Pregnancy and Parturition

“…While the increasing concentration of estrogen stimulates the rise in uterine oxytocin receptors towards the initiation of labor in women and other animal species (Blanks et al, 2003;Spencer et al, 2004), we could not find a correlation between estrogen concentration and the expression of placental OTR mRNA. The placenta is considered to be one of the OT-synthesizing organs responsible for stimulating endometrial PGF2α production, resulting in luteolysis at the beginning of labor (Iliodromiti et al, 2012).…”

Suppressor of cytokine signalling (SOCS) genes are expressed in the endometrium and regulated by conceptus signals during early pregnancy in the ewe

“…Ovine PL begins to be secreted by the trophectoderm at days 15-16 and ovine GH at day 27. Ovine PL binds to a prolactin (PRL) receptor homodimer or a PRL/GH receptor heterodimer whereas GH binds to a GH receptor homodimer, both subunits being expressed in the pregnant ovine endometrium (Spencer et al 2004). Ovine uterus is a rich source of IGF-I and IGF-I receptor is clearly present throughout the first trimester of pregnancy (Wathes et al 1998).…”

Comparative aspects of implantation

“…Endometrial expression of ESR1, PGR, and OXTR is not affected by either ovine PRL3D1 or ovine GH; however, expression of serine protease inhibitor, kunitztype, 1 (SPINT1 or uterine milk proteins) by GE increases in response to both PRL3D1 and GH only if ewes are treated first with intrauterine IFNT between days 11 and 21, and then either PRL3D1 or GH and P 4 daily from days 16 to 29 after onset of estrus (see Spencer et al 2004). However, the mechanism whereby IFNT permits GE to be responsive to PRL3D1 and GH during gestation is not known.…”