Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2α by the uterine endometrium

Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography-tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF 1a (stable metabolite of PGI 2 ) was predominant followed by PGF 2a OPGE 2 OPGD 2 zTXB 2 (stable metabolite of TXA 2 ). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF 2a /PGE 2 ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF 1a (6.4 ng/ml) followed by PGF 2a (1.1 ng/ml) and PGE 2 (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI 2 and PGF 2a receptors were abundantly expressed by the trophoblast, abundant amounts of PGI 2 and PGF 2a in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE 2 in the preimplantation uterus may be essential rather than detrimental for successful reproduction.

Section: Discussionmentioning

confidence: 99%

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Ulbrich¹,

Schülke²,

Groebner³

et al. 2009

“…PGs have pleiotrophic effects in pregnancy and have the potential to influence maternal immune responses , embryo development (Claus et al 1987) and ovarian function (Armstrong 1981, Christenson et al 1994. Most notable is the role of PGF 2a and PGE 2 in the maternal recognition of pregnancy, particularly in view of studies indicating the importance of PGF 2a synthesised by the uterine endometrium (Bazer & Thatcher 1977) and potentially transferred to the ovary by a counter-current mechanism facilitated by close apposition of the uterine venous net to the ovarian artery (Krzymowski et al 1989). In non-mated gilts PGF 2a is the major eicosanoid but in mated gilts peak PG secretion occurs earlier and PGE 2 predominates, antagonising the luteolytic effects of PGF 2a (Christenson et al 1994).…”

Section: Pbs Spmentioning

confidence: 99%

Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig

O’Leary¹,

Jasper²,

Warnes³

et al. 2004

212

179

In pigs, uterine exposure to the constituents of semen is known to increase litter size but the underlying physiological mechanisms remain undefined. Studies in rodents and humans implicate immune modulating moieties in seminal plasma as likely candidates, acting through enhancing the receptivity of the female tract. In this study, the acute and longer term effects of seminal plasma on cytokine expression and leukocyte abundance in the pig endometrium during early pregnancy have been characterised. The reproductive tracts of gonadotrophin-primed pre-pubertal gilts treated with intrauterine infusions of either pooled seminal plasma or phosphate-buffered saline (PBS) were retrieved at 34 h, or on day 5 and day 9 after treatment. Seminal plasma elicited an endometrial inflammatory infiltrate comprised of predominantly macrophages and major histocompatibility complex class II 1 -activated macrophages and dendritic cells. The abundance of these cells was greatest at the pre-ovulatory (34 h) time-point and their increase relative to PBS-treated tissues was maintained until day 9 after seminal plasma treatment. Seminal plasma induced the expression of the cytokines, granulocyte macrophage colony-stimulating factor, interleukin-6 and monocyte chemoattractant protein-1, and the eicosanoid-synthesising enzyme cyclo-oxygenase-2. Expression was maximal 34 h after treatment but altered expression patterns as a consequence of seminal plasma induction persisted through early pregnancy. These changes were accompanied by altered dynamics in pre-implantation embryo development with an increase in the number of embryos and in their viability after seminal plasma treatment. Together, these findings implicate factors in seminal plasma in programming the trajectory of uterine cytokine expression and leukocyte trafficking during early pregnancy and in regulating pre-implantation embryo development in the pig.

“…Pregnancy recognition in the pig results from secretion of estrogens by conceptus trophectoderm between days 11 and 15 of pregnancy, which induces a mechanism to redirect PGF secretion from the uterine vasculature to the uterine lumen (see Bazer & Thatcher 1977). These estrogens also modulate expression of uterine genes considered essential for implantation, and inappropriate exposure of the pregnant uterus to estrogen on days 9 and 10 results in degeneration of pig conceptuses by day 15 (Ross et al 2007).…”

Section: Ifns Estrogens and Uterine Receptivity To Implantation In mentioning

confidence: 99%

“…IFNT silences expression of ESR1 (estrogen receptor a) that precludes estrogen stimulation of expression of oxytocin receptors (OXTR) and, therefore, OXT-induced release of luteolytic pulses of PGF to prevent CL regression (see Bazer et al 2008). In pigs, E 2 , acting in concert with PRL, exerts antiluteolytic effect on uterine epithelia to prevent endocrine release of luteolytic PGF by directing secretion of PGF into the uterine lumen (exocrine release) where it is metabolized (Bazer & Thatcher 1977). Pig conceptus trophectoderm expresses both a type I (IFN d, IFND) and type II (IFN g, IFNG) IFN during the period of conceptus elongation between days 14 and 20 of pregnancy, but neither of these IFNs has been shown to be antiluteolytic (Cencič et al 2003).…”

Section: Maternal Recognition Of Pregnancymentioning

confidence: 99%

Comparative aspects of implantation

Bazer

Spencer²,

Johnson³

et al. 2009

345

285

Uterine receptivity to implantation of blastocysts in mammals includes hatching from zona pellucida, precontact with uterine luminal (LE) and superficial glandular (sGE) epithelia and orientation of blastocyst, apposition between trophectoderm and uterine LE and sGE, adhesion of trophectoderm to uterine LE/sGE, and, in some species, limited or extensive invasion into the endometrial stroma and induction of decidualization of stromal cells. These peri-implantation events are prerequisites for pregnancy recognition signaling, implantation, and placentation required for fetal-placental growth and development through the remainder of pregnancy. Although there is a range of strategies for implantation in mammals, a common feature is the requirement for progesterone (P 4 ) to downregulate expression of its receptors in uterine epithelia and P 4 prior to implantation events. P 4 then mediates its effects via growth factors expressed by stromal cells in most species; however, uterine luminal epithelium may express a growth factor in response to P 4 and/or estrogens in species with a true epitheliochorial placenta. There is also compelling evidence that uterine receptivity to implantation involves temporal and cell-specific expression of interferon (IFN)-stimulated genes that may be induced directly by an IFN or induced by P 4 and stimulated by an IFN. These genes have many roles including nutrient transport, cellular remodeling, angiogenesis and relaxation of vascular tissues, cell proliferation and migration, establishment of an antiviral state, and protection of conceptus tissues from challenges by the maternal immune cells.