scholarly journals 003.Uterine and placental factors regulating conceptus growth: insights from the ewe

2004 ◽  
Vol 16 (9) ◽  
pp. 3
Author(s):  
T. E. Spencer

Uterine adenogenesis is the process whereby endometrial glands differentiate and develop and is primarily a postnatal event in all mammals. In domestic animals and humans, adenogenesis involves initial differentiation and budding of glandular epithelium followed by invagination and extensive tubular coiling and branching morphogenesis through the endometrial stroma to the myometrium. Transient exposure of the neonatal ewe to a progestin from birth to postnatal Day 56 resulted in a uterine gland knock out (UGKO) phenotype in the adult. UGKO ewes exhibit a peri-implantation defect in conceptus (embryo/fetus and associated extraembryonic membranes) survival, indicating the functional importance of uterine glands and their secretions. Genomic and proteomic analysis of uterine endometrium from UGKO ewes has identified many candidate genes that regulate conceptus development and implantation, including endogenous Jaagsiekte sheep retroviruses (enJSRVs), glycosylated cell adhesion molecule one (GlyCAM-1), osteopontin and galectin-15. Galectin-15, also known as OVGAL11, and a previously uncharacterised member of the galectin family of secreted β-galactoside lectins, was discovered in the endometrium of sheep. In endometria of cyclic and pregnant sheep, galectin-15 mRNA was expressed specifically in the endometrial luminal epithelium but not in the conceptus. In pregnant sheep, galectin-15 mRNA expression appeared in the epithelia between Days 10 and 12 and increased between Days 12 and 16. Progesterone induced and interferon tau stimulated galectin-15 mRNA in the endometrial epithelium. Galectin-15 protein was concentrated near and on the apical surface of the endometrial luminal epithelia and localised within discrete cytoplasmic crystalline structures of conceptus trophectoderm. Galectin-15 is hypothesised to function extracellularly to regulate trophectoderm migration and adhesion to the endometrial epithelium and intracellularly to regulate cell survival, growth and differentiation. In sheep, the sequential actions of ovarian steroid hormones (oestrogen and progesterone), interferon tau, placental lactogen and placental growth hormone constitute a servomechanism that directly regulates endometrial gland morphogenesis and terminal differentiated function to provide increasing histotrophic nutrition for conceptus growth and development. Knowledge gained from this research will be used to prevent or treat infertility, fetal growth retardation and disease in domestic animals and humans.

2021 ◽  
Author(s):  
◽  
Eleanore V. O'Neil

In sheep, pregnancy establishment encompasses conceptus elongation, implantation, and placentation. These events are regulated by factors present within the uterine luminal fluid (ULF) from the endometrial epithelium and the conceptus itself that affect proliferation, migration, attachment, and adhesion of the conceptus trophectoderm. As the peri-implantation period is especially susceptible to pregnancy loss, it is essential to understand the various components and functional roles of substances within the ULF. The central hypothesis of this dissertation is that lipids and lipid associated macromolecules are components of the ULF and mediate endometrial-embryonic crosstalk and regulate conceptus development. This work sought to identify, characterize, and/or determine the roles of: (1) extracellular vesicles (EVs); (2) lipids and metabolites; (3) prostaglandins (PGs); and (4) apolipoproteins present within the ULF of ewes during early gestation. Collectively, the present studies established that: (1) EVs increase within the ULF during the estrous cycle but are depleted in the uterine lumen of pregnant ewes due to uptake by the elongating conceptus; (2) the lipid and protein cargo of uterine EVs is diverse and altered by pregnancy; (3) uterine EVs regulate cellular processes in the conceptus trophectoderm and endometrium including cell proliferation and secretions; (4) various lipids (specifically phospholipids, ceramides, and triglycerides) and metabolites are elevated in the ULF of pregnant ewes; (5) the conceptus lipidome and metabolome is distinct from the ULF and endometrium suggesting selective uptake of ULF substances; (6) the production of PGs by PTGS2 in the conceptus is not required for conceptus elongation; (7) the secretion of APOA1 by the conceptus does not mobilize endometrial lipids into the ULF and is not required for early pregnancy development or survival. Collectively, these studies highlight the complex and dynamic composition of the ULF and support the overall hypothesis that lipids and lipid-associated macromolecules are critical components of the ULF that mediate conceptus-endometrial crosstalk and regulate important developmental processes in the conceptus. Future investigation and expansion of these findings will fill crucial gaps in our knowledge of early pregnancy events and may provide biomarkers or help develop therapies to improve pregnancy outcomes and reproductive efficiency in agricultural species.


2020 ◽  
Author(s):  
Haidee Tinning ◽  
Alysha Taylor ◽  
Dapeng Wang ◽  
Bede Constantinides ◽  
Ruth Sutton ◽  
...  

ABSTRACTDuring the pre-implantation period of pregnancy in eutherian mammals, changes to the uterine endometrium are required (both at the transcriptional and protein level) to facilitate the endometrium becoming receptive to an implanting embryo. We know that the developing conceptus (embryo and extraembryonic membranes) produces proteins during this developmental stage. We hypothesised that this common process in early pregnancy in eutheria may be facilitated by highly conserved conceptus-derived proteins such as macrophage capping protein CAPG. More specifically, we propose that CAPG may share functionality in modifying the transcriptome of the endometrial epithelial cells to facilitate receptivity to implantation in species with different implantation strategies, such as human and bovine. A recombinant bovine form of CAPG (91% sequence identity between bovine and human) was produced and bovine endometrial epithelial (bEECs) and stromal (bESCs) cells and human endometrial epithelial cells (hEECs) were cultured for 24 h with or without rbCAPG. RNA sequencing and quantitative real-time PCR analysis was used to assess the transcriptional response to rbCAPG (Control, vehicle, CAPG 10, 100, 1000 ng/ml: n=3 biological replicates per treatment per species). Treatment of bEECs with CAPG resulted in changes to 1052 transcripts (629 increased and 423 decreased) compared to vehicle controls, including those previously only identified as regulated by interferon-tau, the pregnancy recognition signal in cattle. Treatment of hEECs with bovine CAPG increased expression of transcripts previously known to interact with CAPG in different systems (CAPZB, CAPZA2, ADD1 and ADK) compared with vehicle controls (P<0.05). In conclusion, we have demonstrated that CAPG, a highly conserved protein in eutherian mammals elicits a transcriptional response in the endometrial epithelium in two species with different implantation strategies that may facilitate uterine receptivity.


2013 ◽  
Vol 25 (1) ◽  
pp. 202
Author(s):  
L. O'Hara ◽  
N. Forde ◽  
D. Rizos ◽  
V. Maillo ◽  
A. D. Ealy ◽  
...  

The aim of this study was to investigate the effect of short term progesterone (P4) supplementation on circulating P4 concentrations, corpus luteum (CL) size, and conceptus development in cattle. The oestrous cycles of crossbred beef heifers were synchronised using a 7-day PRID® Delta (1.55 g P4) treatment with administration of a PGF2α analog (Enzaprost®) the day before PRID® Delta removal. Only those recorded in standing oestrus (Day 0) were used. In Experiment 1, heifers were randomly assigned to 1 of 5 groups: (1) control: no treatment, (2) placebo: insertion of a blank device (no P4) from Day 3 to 7, (3) insertion of a PRID® Delta from Day 3 to 7, (4) insertion of a PRID® Delta from Day 3 to 5, or (v5) insertion of a PRID® Delta from Day 5 to 7. In vitro produced blastocysts were transferred to each heifer on Day 7 (10 blastocysts per heifer) and conceptuses were recovered at slaughter on Day 14. In Experiment 2 heifers were artificially inseminated at oestrus and randomly assigned to 1 of 3 treatment groups (1) placebo, (2) PRID® Delta from Day 3 to 5, or (3) PRID® Delta from Day 3 to 7. All heifers were slaughtered on Day 16, and recovered conceptuses were incubated in synthetic oviduct fluid medium for 24 h; spent media and uterine flushes were analysed for interferon-tau (IFNT). In both experiments, daily blood samples were taken to measure serum P4 concentration. Data were analysed using the PROC MIXED procedure of SAS (SAS Institute Inc., Cary, NC, USA). Insertion of a PRID® Delta resulted in an increase (P < 0.05) in serum P4, which declined following removal. In Experiment 1, serum P4 concentration was significantly lower from Day 9 to 14 (P < 0.05) and Day 14 CL weight was lower in the PRID® Delta Day 3 to 7 group than the placebo or control groups. P4 supplementation from Day 3 to 5 (17.0 ± 1.4 mm) or Day 3 to 7 (11.3 ± 2.3 mm) increased conceptus length compared to the placebo (2.1 ± 1.8 mm). In Experiment 2, serum P4 was significantly lower in the two supplemented groups following PRID® Delta removal compared with the placebo (P < 0.05) and was associated with a lower CL weight in the Day 3 to 7 group. Supplementation from Day 3 to 5 (94.0 ± 18.8 mm) or Day 3 to 7 (143.6 ± 20.6 mm) increased conceptus length on Day 16 compared to the placebo (50.3 ± 17.4 mm). Conceptus length was strongly correlated with the concentration of IFNT in the uterine flush (r = 0.58; P = 0.011) and spent culture medium (r = 0.68; P < 0.002). These findings highlight the somewhat paradoxical effects of P4 supplementation when given in the early metoestrus period in terms of its positive effect on conceptus development and its potentially negative effects on CL lifespan. Supported by CEVA Sante Animale and Science Foundation Ireland (07/SRC/B1156).


1986 ◽  
Vol 251 (3) ◽  
pp. E328-E333 ◽  
Author(s):  
M. Freemark ◽  
M. Comer ◽  
S. Handwerger

To determine whether changes in the relative biological potencies of ovine placental lactogen (oPL) and ovine growth hormone (oGH) during development derive from ontogenetic changes in the binding of these hormones to hepatic receptors, we have compared the binding of 125I-oPL and 125I-oGH to hepatic membranes from fetal lambs and pregnant sheep at mid- and late gestation and from postnatal sheep at 1 day to 7 mo of age. Specific high-affinity 125I-oPL binding sites in ovine fetal liver were detected as early as day 70 of gestation (term = 145 days), and the number of fetal 125I-oPL binding sites increased progressively throughout the latter half of gestation, reaching a maximum (11.2 fmol/mg protein) at 3-7 days before parturition. The potency of oPL (Kd 0.27 nM) in competing for 125I-oPL binding sites was 90 and 1,300 times greater than that of oGH and ovine prolactin, respectively. Although the number of fetal 125I-oPL binding sites increased throughout pregnancy, there was little or no specific binding of 125I-oGH noted in the fetus. Treatment of fetal liver membranes with 4 M MgCl2 did not enhance the subsequent specific binding of 125I-oGH, suggesting that the low specific binding of oGH did not result from occupation of hepatic receptors by endogenous circulating oPL or oGH. In contrast, MgCL2 treatment markedly increased the apparent number of fetal 125I-oPL binding sites, suggesting that oPL receptors in fetal liver are partly saturated in vivo by oPL.(ABSTRACT TRUNCATED AT 250 WORDS)


Endocrinology ◽  
2012 ◽  
Vol 154 (2) ◽  
pp. 931-941 ◽  
Author(s):  
Piotr Dorniak ◽  
Thomas H. Welsh ◽  
Fuller W. Bazer ◽  
Thomas E. Spencer

During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto-reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation. The primary aim of these studies was to test the hypothesis that HSD11B1-derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep. In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Some effects of cortisol and IFNT were mediated by PTGS2-derived PG. In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating. Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF-infused ewes. These results suggest that HSD11B1-derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.


1987 ◽  
Vol 113 (2) ◽  
pp. 277-283 ◽  
Author(s):  
G. Thordarson ◽  
G. H. McDowell ◽  
S. V. Smith ◽  
S. Iley ◽  
I. A. Forsyth

ABSTRACT Continuous intravenous infusions of saline or of a placental extract containing ovine placental lactogen were given to three non-pregnant, non-lactating ewes over periods of 36 h, 1 week apart. During saline infusion no placental lactogen was detected in jugular vein plasma, but infusion of the placental extract raised the placental lactogen concentration from undetectable to 40-50 μg/l, similar to concentrations in ewes with one fetus on day 90 of pregnancy. By comparison with the saline control period, infusion of the placental extract consistently increased both plasma concentrations and irreversible loss of non-esterified fatty acids. Plasma concentrations of glucose and urea, but not irreversible loss of these metabolites, were consistently increased. Although the placental extract was not subjected to extensive purification, it was enriched in placental lactogen and contained no detectable contamination with insulin, prolactin or growth hormone. The results are suggestive of a role for placental lactogen in modifying metabolism and acting during pregnancy to provide nutrients for fetal metabolism. J. Endocr. (1987) 113, 277–283


2018 ◽  
Author(s):  
◽  
Joao Gabriel Nascimento Moraes

Infertility and subfertility represent pervasive problems in domestic animals and humans, and embryonic mortality is a major factor influencing reproductive efficiency. In cattle, the majority of embryonic loss occurs during the first month of gestation that involves the period of blastocyst formation, conceptus elongation, maternal recognition of pregnancy, implantation and beginning of placentation. Pregnancy success and embryonic mortality are affected by paternal, maternal, embryonic, and environmental factors, and the establishment and maintenance of pregnancy are a result of complex conceptus-endometrium interactions that results in adequate conceptuses (embryo/fetus and associated extraembryonic membranes) development, implantation and placentation. Our central hypothesis is that the uterus directly influences embryonic and conceptus development, and we proposed that heifers with consistently high or low fertility have distinct uterine capacity to support pregnancy. To test this hypothesis, serial embryo transfer (3-4 rounds) was used to classify heifers based on pregnancy success on day 28 as high fertile (HF; 100%), subfertile (SF; 25%), or infertile (IF; 0%). Next, a series of experiments were conducted using the fertility-classified heifers to investigate conceptus development and uterine biology in two time points: (1) day 14, to investigate conceptus development prior to the period when pregnancy induce changes are detected in the endometrium transcriptome; (2) at day 17, to evaluate conceptus-endometrial cross talk during the period of maternal recognition of pregnancy. Results from the studies conducted on day 14 supports the idea that: (1) circulating progesterone concentrations are not different among fertility-classified heifers; (2) conceptus development and survival by day 14 is not affected by fertility classification; (3) only minimal differences in endometrium transcriptome are detected among pregnant fertility-classified heifers. Collectively, these results indicated that the biological mechanisms underlying subfertility and infertility manifests between days 14 and 28, when pregnancy recognition signaling and conceptus elongation and implantation must occur for the establishment of pregnancy. Moreover, results from the subsequent experiments conducted at day 17 indicated that: (1) the mechanism of pregnancy loss in fertility-classified heifers start to manifest around the time of maternal recognition of pregnancy; (2) conceptus survival by day 17 is compromised in IF heifers; (3) conceptus development is advanced in HF than SF heifers; (4) conceptus transcriptome is directly influenced by the uterine environment; (5) dysregulated conceptus-endometrial interactions in SF heifers seems to be the major cause of pregnancy loss. Analysis of the uterine luminal fluid (ULF) from fertility classified heifers on day 17 established that: (1) ULF composition is affected by conceptus-endometrium interactions; (2) glucose concentrations in ULF are not different among fertility-classified heifers; (3) pregnancy induced changes in the metabolites found in ULF was diminished in SF heifers, and the majority of the metabolites that increased in the ULF of pregnant HF than SF heifers were associated with energy and amino acid metabolism; (4) increased abundance of proteins involved with energy metabolism, oxidative stress, amino acid metabolism, and cell proliferation and differentiation were detected in ULF of pregnant HF than SF heifers; (5) The lipid content of the ULF is altered by pregnancy and fertility classification; (6) overall concentrations prostaglandins and interferon tau were increased in the uterine lumen of pregnant HF than SF heifers, likely due to differences in conceptus size. Collectively, results from these studies supports the idea that the dysregulated conceptus-endometrium interactions in SF heifers affects the uterine luminal contents and impairs conceptus survival and elongation. Furthermore, knowledge gained from these studies enhances our understanding of the mechanisms regulating pregnancy loss in cattle and provides new information on uterine and conceptus biology during early pregnancy in ruminants.


2018 ◽  
Vol 1 (4) ◽  
pp. 301-309
Author(s):  
Mariana Rojas ◽  
Ángel Rodríguez

In vertebrates, depending on the environment in which an embryo develops, different types of extraembryonic membranes are formed. In placental mammals the following extraembryonic membranes are formed: amnion, yolk sac, allantois, chorion and placenta. Extraembryonic membranes perform functions vital to the embryo. The amnion protects the embryo from drying, the mechanical trauma, temperature changes and adhesions which can distort it. The yolk sac is present in all vertebrates. In mammals allows the formation of the first blood vessels and the first blood, home to the primordial germ cells for some time; however, in fish and birds these have nutritional importance. In birds and mammals such as cattle, sheep and pig the allantois receives urinary wastes; this structure also contributes part of the bladder and at the time of birth becomes the suspensory ligament, urachus. The chorion form chorionic villus, which can produce hormones such as chorionic gonadotropin and human placental lactogen. A portion of the chorionic sac helps form the placenta.


2009 ◽  
Vol 21 (1) ◽  
pp. 152
Author(s):  
N. V. Hanh ◽  
Q. X. Huu ◽  
N. T. Uoc ◽  
J. Sulon ◽  
N. M. Sausa ◽  
...  

Ruminant placental lactogens (PL) are members of the growth factor/prolactin (GH/PRL) family. They are synthesized by trophectodermal binucleate cells. There is evidence to suggest that PL is involved in control of fetal growth, through actions in both the maternal and fetal compartments, as well as in influencing mammary growth during pregnancy (Byatt JC et al. 1992 J. Anim. Sci. 70, 2911–2923). The structure and biology of PL have been studied in the cow, sheep, goat, human, and mice. The maternal concentration of PL is 100- to 1 000-fold greater in pregnant sheep and goats than in cows but no information exists about PL concentration in buffalo. The aim of the present study was to evaluate the ability to detect PL in buffalo fluids by using bovine PL antibody. Samples were collected in the slaughterhouse immediately after animal slaughter. The fetuses were measured after heart blood collection. A bPL RIA system was used to determine the bPL concentrations in the buffalo samples (Alvarez-Oxiley AV et al. 2007 Reprod. Fertil. Dev. 19, 877–885). The rbPL molecules were radio-iodinated with [125]I-Na by using the lactoperoxidase method (Thorell JI and Johansson BG 1971 Biochim. Biophys. Acta 251, 363–369). Concentrations of buffalo PL are presented in Table 1. In this RIA system, the minimum detected value was 0.068 ng mL–1, and the binding competition curves of bovine PL standard and buffalo fluids dilution using bovine PL antibody were paralleled in all kinds of samples. The lowest concentration was detected in allantoid fluid and the greatest concentration in fetal plasma (P < 0.05). Study of the biology of PL in buffalo has proved difficult because the concentration of PL in all buffalo fluids is very low. Furthermore, the research concerning buffalo PL function required in vivo experiments. Existing data suggest that at least the concentration of buffalo PL is different from cattle and other smaller domestic ruminants. In conclusion, our results provide preliminary information about concentrations of PL in buffalo fluids. Table 1.Concentration of placental lactogen in buffalo fluids This work was supported by a grant from the Belgian Technical Cooperation.


Placenta ◽  
2002 ◽  
Vol 23 (8-9) ◽  
pp. 613-630 ◽  
Author(s):  
H. Miyazaki ◽  
M. Imai ◽  
T. Hirayama ◽  
S. Saburi ◽  
M. Tanaka ◽  
...  

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