Fetal-maternal interactions during the establishment of pregnancy in ruminants.
ABSTRACT This review integrates established information with new insights into molecular and physiological mechanisms responsible for events leading to pregnancy recognition, endometrial receptivity, and implantation with emphasis on sheep. After formation of the corpus luteum, progesterone acts on the endometrium and stimulates blastocyst growth and elongation to form a filamentous conceptus (embryo/fetus and associated extraembryonic membranes). Recurrent early pregnancy loss in the uterine gland knockout ewe model indicates that endometrial epithelial secretions are essential for peri-implantation blastocyst survival and growth. The elongating sheep conceptus secretes interferon tau (IFNT) that acts on the endometrium to inhibit development of the luteolytic mechanism by inhibiting transcription of the estrogen receptor alpha (ESR1) gene in the luminal (LE) and superficial ductal glandular (sGE) epithelia, which prevents estrogen-induction of oxytocin receptors (OXTR) and production of luteolytic prostaglandin F2-alpha pulses. Progesterone downregulates its receptors (PGR) in LE and then GE, correlating with a reduction of anti-adhesive MUC1 (mucin glycoprotein one) and induction of secreted LGALS15 (galectin 15) and SPP1 (secreted phosphoprotein one), that are proposed to regulate trophectoderm growth and adhesion. IFNT acts on the LE to induce WNT7A (wingless-type MMTV integration site family member 7A) and to stimulate LGALS15, CTSL (cathepsin L), and CST3 (cystatin C), which may regulate conceptus development and implantation. During the peri-implantation period, trophoblast giant binucleate cells (BNC) begin to differentiate from mononuclear trophectoderm cells, migrate and then fuse with the uterine LE as well as each other to form multinucleated syncytial plaques. Trophoblast giant BNC secrete chorionic somatomammotropin (CSH1 or placental lactogen) that acts on the endometrial glands to stimulate their morphogenesis and differentiated function. The interactive, coordinated and stage-specific effects of ovarian and placental hormones regulate endometrial events necessary for fetal-maternal interactions and successful establishment of pregnancy.
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ABSTRACT: The maternal recognition of pregnancy is the period when the conceptus signals its presence to the mother. This is an important moment of pregnancy, which can be decisive for the progress of pregnancy. During gestation, there is a series of events involving progesterone and prostaglandins produced by corpus luteum, a temporary gland formed from a single ovulation follicle. The progesterone produced by corpus luteum is a steroid involved in both ovarian cyclicity and the establishment and maintenance of pregnancy in most mammals. Some peculiarities of the events involved in the maternal-fetal relationship during pregnancy recognition among domestic species have been discussed in this review, one of them is the key role of interferon-tau protein (INF-T) protein that has proven antiluteolytic function and that is associated with maternal recognition of pregnancy in ruminants; the movement of the equine embryo in order to maintain its signaling; the estrogens produced by the pig fetuses, which have luteotrophic function for this species, but also has luteolytic function in others species. O reconhecimento materno da gestação é o período em que o concepto sinaliza a sua presença para a mãe. Esse é um importante momento da gestação, que pode ser decisivo para o progresso da prenhez. Durante a gestação, ocorre uma série de eventos hormonais, envolvendo progesterona e prostaglandinas, sendo fundamental a função do corpo lúteo, uma glândula temporária formada a partir da ovulação de um folículo. O corpo lúteo produz a progesterona, esteroide envolvido tanto na ciclicidade ovariana quanto no estabelecimento e manutenção da gestação, na maioria dos mamíferos. Algumas particularidades dos eventos envolvidos na relação materno-fetal durante o reconhecimento da gestação em espécies domésticas foram abordadas nesta revisão; entre estas, foi descrito o papel fundamental da proteína interferon-tau (INF-T) com ação antiluteolítica comprovada e que está associada ao reconhecimento materno da gestação em ruminantes; a movimentação do embrião equino, mantendo a sua sinalização; os estrogênios produzidos pelos conceptos suínos com função luteotrófica para a espécie, mas que também possui função luteolítica em outras espécies.
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ABSTRACT: The majority of pregnancy loss in ruminants occurs during the first three weeks after conception, particularly during the period of conceptus elongation that occurs prior to pregnancy recognition and implantation. This review integrates established and new information on the biological role of ovarian progesterone (P4), prostaglandins (PGs), interferon tau (IFNT) and cortisol in endometrial function and conceptus elongation. Progesterone is secreted by the ovarian corpus luteum (CL) and is the unequivocal hormone of pregnancy. Prostaglandins (PGs) and cortisol are produced by both the epithelial cells of the endometrium and the trophectoderm of the elongating conceptus. In contrast, IFNT is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signal that inhibits production of luteolytic pulses of PGF2α by the endometrium to maintain the CL and thus production of P4. Available results in sheep support the idea that the individual, interactive, and coordinated actions of P4, PGs, IFNT and cortisol regulate conceptus elongation and implantation by controlling expression of genes in the endometrium and/or trophectoderm. An increased knowledge of conceptus-endometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent early pregnancy loss and provide new strategies to improve fertility and thus reproductive efficiency.01/2014; 5(1):53. DOI:10.1186/2049-1891-5-53
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ABSTRACT: The ovine blastocyst hatches from the zona pellucida by Day 8 and develops into an ovoid or tubular conceptus (embryo and associated extraembryonic membranes) that grows and elongates into a filamentous form between Days 12 and 16. The trophectoderm of the elongating conceptus synthesizes and secretes interferon tau (IFNT) as well as prostaglandins (PGs) via prostaglandin synthase two (PTGS2). Intrauterine infusion of a PTGS2 inhibitor prevents conceptus elongation in sheep. Although many PGs are secreted, PGI2 and PGJ2 can activate nuclear peroxisome proliferator activator receptors (PPARs) that heterodimerize with retinoic X receptors (RXRs) to regulate gene expression and cellular function. Expression of PPARD, PPARG, RXRA, RXRB and RXRG is detected in the elongating ovine conceptus, and nuclear PPARD and PPARG are present in the trophectoderm. Consequently, PPARD and PPARG are hypothesized to have essential roles in conceptus elongation in ruminants. In utero loss-of-function studies of PPARD and PPARG in the ovine conceptus trophectoderm were conducted using morpholino antisense oligonucleotides (MAO) that inhibit mRNA translation. Elongating, filamentous type conceptuses were recovered from ewes infused with a control morpholino or PPARD MAO. In contrast, PPARG MAO resulted in severely growth-retarded conceptuses or conceptus fragments with apoptotic trophectoderm. In order to identify PPARG regulated genes, PPARG ChIP-Seq and RNA-Seq were conducted using Day 14 ovine conceptuses. These analyses revealed candidate PPARG-regulated genes involved in biological pathways including lipid and glucose uptake, transport, and metabolism. Collectively, results support the hypothesis that PTGS2-derived PGs and PPARG are essential regulators of conceptus elongation with specific roles in trophectoderm survival and proliferation. Copyright 2014 by The Society for the Study of Reproduction.Biology of Reproduction 12/2014; 92(2). DOI:10.1095/biolreprod.114.123877 · 3.45 Impact Factor