scholarly journals Cortisol and Interferon Tau Regulation of Endometrial Function and Conceptus Development in Female Sheep

Endocrinology ◽  
2012 ◽  
Vol 154 (2) ◽  
pp. 931-941 ◽  
Author(s):  
Piotr Dorniak ◽  
Thomas H. Welsh ◽  
Fuller W. Bazer ◽  
Thomas E. Spencer
Keyword(s):  
Early Pregnancy ◽  
Reductase Activity ◽  
In Utero ◽  
Selective Inhibitor ◽  
Biological Role ◽  
Interferon Tau ◽  
Uterine Lumen ◽  
Conceptus Development ◽  
Female Sheep ◽  
Expression And Activity

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.

scholarly journals Progesterone and interferon tau-regulated genes in the ovine uterine endometrium: identification of periostin as a potential mediator of conceptus elongation

Reproduction ◽  
2009 ◽  
Vol 138 (5) ◽  
pp. 813-825 ◽  
Author(s):  
Hyo Won Ahn ◽  
Jennifer L Farmer ◽  
Fuller W Bazer ◽  
Thomas E Spencer
Keyword(s):  
Early Pregnancy ◽  
Calcium Binding ◽  
Collagen Type ◽  
Cdna Array ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
S100 Calcium Binding Protein ◽  
Trophectoderm Cells ◽  
Conceptus Development

During early pregnancy in ruminants, progesterone (P4) and interferon tau (IFNT) act on the endometrium to regulate genes hypothesized to be important for conceptus development and implantation. The present study was conducted to verify several candidate genes (actin α-2, smooth muscle, aorta (ACTA2), collagen, type III, α-1 (COL3A1), periostin (POSTN), secreted protein acidic cysteine-rich (SPARC), S100 calcium-binding protein A2 (S100A2),STAT5Aand transgelin (TAGLN)) regulated by pregnancy, P4, and/or IFNT in the endometrium determined using a custom ovine cDNA array.S100A2mRNA was detected primarily in endometrial epithelia and conceptuses.S100A2mRNA increased in endometrial epithelia from days 10 to 16 in cyclic ewes and from days 10 to 14 in pregnant ewes and declined thereafter. The abundance ofS100A2mRNA was less in endometrial luminal epithelium of IFNT-infused ewes receiving P4. Expression ofCOL3A1, SPARC, ACTA2, andTAGLNwas independent of pregnancy, P4, or IFNT.POSTNmRNA was detected primarily in compact stroma of intercaruncular and caruncular endometria, but not in the conceptus. EndometrialPOSTNmRNA increased between days 12 and 14 in pregnant but not cyclic ewes, andPOSTNmRNA was more abundant in uterine stroma of ewes treated with P4. POSTN protein was detected in uterine flushings of pregnant ewes and found to mediate attachment and stimulate migration of ovine trophectoderm cellsin vitro. These results support the ideas that POSTN and S100A2 are regulated by P4and IFNT respectively, and that POSTN is involved in conceptus elongation during early pregnancy.

scholarly journals Analysis of the uterine lumen in fertility-classified heifers: II. Proteins and metabolites†

2019 ◽  
Vol 102 (3) ◽  
pp. 571-587 ◽  
Author(s):  
Joao G N Moraes ◽  
Susanta K Behura ◽  
Jeanette V Bishop ◽  
Thomas R Hansen ◽  
Thomas W Geary ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Uterine Receptivity ◽  
Interferon Tau ◽  
Uterine Lumen ◽  
Interferon Stimulated Genes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Conceptus Development

Abstract Survival and growth of the bovine conceptus is dependent on endometrial secretions or histotroph. Previously, serial blastocyst transfer was used to classify heifers as high fertile (HF), subfertile (SF), or infertile (IF). Here, we investigated specific histotroph components (proteins and metabolites) in the uterine lumen of day 17 fertility-classified heifers. Interferon tau (IFNT) was more abundant in uterine lumenal fluid (ULF) of pregnant HF than SF animals as the conceptus was longer in HF heifers. However, no differences in endometrial expression of selected classical and nonclassical interferon-stimulated genes (ISGs) were observed, suggesting that IFNT signaling in the endometrium of pregnant HF and SF heifers was similar. Pregnancy significantly increased the abundance of several proteins in ULF. Based on functional annotation, the abundance of a number of proteins involved in energy metabolism, oxidative stress, amino acid metabolism, and cell proliferation and differentiation were greater in the ULF of pregnant HF than SF heifers. Metabolomics analysis found that pregnancy only changed the metabolome composition of ULF from HF heifers. The majority of the metabolites that increased in the ULF of pregnant HF as compared to SF heifers were associated with energy and amino acid metabolism. The observed differences in ULF proteome and metabolome are hypothesized to influence uterine receptivity with consequences on conceptus development and survival in fertility-classified heifers.

Production of interferon by red deer (Cervus elaphus) conceptuses and the effects of roIFN-tau on the timing of luteolysis and the success of asynchronous embryo transfer

Reproduction ◽  
2000 ◽  
pp. 387-395 ◽  
Author(s):  
KJ Demmers ◽  
HN Jabbour ◽  
DW Deakin ◽  
AP Flint
Keyword(s):  
Embryo Transfer ◽  
Early Pregnancy ◽  
Cervus Elaphus ◽  
Pregnancy Loss ◽  
Red Deer ◽  
Interferon Tau ◽  
Recombinant Interferon ◽  
Uterine Flushing ◽  
Calving Rate

The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.

scholarly journals Recent Possibilities for the Diagnosis of Early Pregnancy and Embryonic Mortality in Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1666
Author(s):  
Ottó Szenci
Keyword(s):  
Blood Flow ◽  
Dairy Cows ◽  
Early Pregnancy ◽  
Fetal Mortality ◽  
Reproductive Efficiency ◽  
Interferon Tau ◽  
Early Pregnancy Factor ◽  
Pelvic Inlet ◽  
On Farm ◽  
Protein Assays

One of the most recent techniques for the on-farm diagnosis of early pregnancy (EP) in cattle is B-mode ultrasonography. Under field conditions, acceptable results may be achieved with ultrasonography from Days 25 to 30 post-AI. The reliability of the test greatly depends on the frequency of the transducer used, the skill of the examiner, the criterion used for a positive pregnancy diagnosis (PD), and the position of the uterus in the pelvic inlet. Non-pregnant animals can be selected accurately by evaluating blood flow in the corpus luteum around Day 20 after AI, meaning we can substantially improve the reproductive efficiency of our herd. Pregnancy protein assays (PSPB, PAG-1, and PSP60 RIA, commercial ELISA or rapid visual ELISA tests) may provide an alternative method to ultrasonography for determining early pregnancy or late embryonic/early fetal mortality (LEM/EFM) in dairy cows. Although the early pregnancy factor is the earliest specific indicator of fertilization, at present, its detection is entirely dependent on the use of the rosette inhibition test; therefore, its use in the field needs further developments. Recently found biomarkers like interferon-tau stimulated genes or microRNAs may help us diagnose early pregnancy in dairy cows; however, these tests need further developments before their general use in the farms becomes possible.

Vertebral malformation in the mouse foetus caused by X-radiation of the mother during pregnancy

Development ◽  
1964 ◽  
Vol 12 (4) ◽  
pp. 841-850
Author(s):  
Ujihiro Murakami ◽  
Yoshiro Kameyama
Keyword(s):  
Early Pregnancy ◽  
Vertebral Column ◽  
Strain Differences ◽  
In Utero ◽  
Oxygen Deprivation ◽  
Experimental Animals ◽  
Vertebral Malformation ◽  
Pregnant Mice ◽  
Maternal Hypoxia ◽  
In Pregnancy

Maternal hypoxia in early pregnancy can result in malformations of the vertebrae of mouse foetuses, and there is a tendency for more posterior vertebrae to be affected the later in pregnancy the oxygen deprivation occurs (Murakami & Kameyama, 1963). Ingalls et al. (1957) and Degenhardt (1954, 1959) had earlier obtained similar results. We have also exposed pregnant mice to X-radiation and studied the consequent malformations. The effects on the extremities have already been described (Murakami, Kameyama & Nogami, 1963), and in the present paper we shall describe the effects on the vertebral column. Vertebral malformations in animals irradiated in utero have been described by Job, Leibold & Fitzmaurice (1935), Warkany and Schraffenberger (1947), Russell. (1950, 1954), and Russell & Russell (1954). In order to obtain results comparable with those of our experiments with hypoxia, no less than to detect inter-strain differences, we used mice of the ddN and CF1 strains originally supplied by the Central Laboratories for Experimental Animals, Tokyo (Zikkendobutsu Chuo Kenkyujo).

Nutrition and early pregnancy in beef heifers: impacts on CAT2 abundance in utero-placental tissues

2019 ◽  
Author(s):  
A.C.B. Menezes ◽  
T.L. Neville ◽  
M.S. Crouse ◽  
K.J. McLean ◽  
A.K. Ward ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
In Utero ◽  
Beef Heifers

scholarly journals Response to the gonadotropin releasing hormone agonist leuprolide in immature female sheep androgenized in utero

2005 ◽  
Vol 38 (2-3) ◽  
Author(s):  
SERGIO E RECABARREN ◽  
TERESA SIR-PETERMANN ◽  
ALEJANDRO LOBOS ◽  
ETHEL CODNER ◽  
PEDRO P ROJAS-GARCÍA ◽  
...  
Keyword(s):  
In Utero ◽  
Gonadotropin Releasing Hormone ◽  
Immature Female ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Female Sheep

scholarly journals The effect of pregnancy on the expression of uterine oxytocin, oestrogen and progesterone receptors during early pregnancy in the cow

1999 ◽  
Vol 160 (1) ◽  
pp. 21-33 ◽  
Author(s):  
RS Robinson ◽  
GE Mann ◽  
GE Lamming ◽  
DC Wathes
Keyword(s):  
Cross Sections ◽  
Early Pregnancy ◽  
In Situ Hybridisation ◽  
Progesterone Receptors ◽  
Prostaglandin F2alpha ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
Low Concentrations ◽  
Oxytocin Antagonist

The expression of oxytocin receptor (OTR) in the uterine endometrium plays an important role in the initiation of luteolysis. During early pregnancy, the conceptus secretes interferon tau (IFN|gt) which inhibits OTR up-regulation and luteolysis. In this study, uterine horn cross sections were collected on day 16 from 15 pregnant cows (PREG), 9 uninseminated controls and 5 inseminated cows with no embryo present. The latter two groups had similar results and were combined to form a single non-pregnant (NP) group. The animals were given an oxytocin challenge shortly before tissue collection to assess prostaglandin F2alpha (PGF2alpha) release through the measurement of the metabolite 13,14-dihydro-15-keto PGF2alpha (PGFM). The mRNAs for OTR, oestrogen receptor (ER) and progesterone receptor (PR) were localised by in situ hybridisation. The results were quantified by optical density (OD) measurements from autoradiographs using image analysis. OTR protein was measured by autoradiography with iodinated oxytocin antagonist and ER and PR protein was detected by immunocytochemistry. The release of PGFM after the oxytocin challenge was significantly higher in the 14 NP cows (187%+/-15%) compared with the PREG group (131%+/-11%) (P<0.01). Low concentrations of OTR mRNA were localised to the luminal epithelium (LE) in 6 out of the 14 NP cows, of which 2 also expressed OTR protein, while OTR mRNA and protein were undetectable in all the pregnant animals. These results indicated that the sampling time coincided with the onset of the luteolytic mechanism in the NP cows. On day 16 ER mRNA was detectable in both the LE and glands of both PREG and NP animals. There were no differences in either ER mRNA or protein between NP and PREG samples. PR mRNA was moderately expressed in the caruncular stroma, with lower levels in the dense caruncular-like stroma and glands. There were no differences between PREG and NP animals. The expression of PR mRNA and protein in the deep glands was variable between animals. These results suggested that, in cows, the presence of an embryo suppressed the expression of OTR, but had no effect on the expression of the transcriptionally regulated ER on day 16.

scholarly journals In Utero Exposure to 17α-Hydroxyprogesterone Caproate May Contribute to Increasing Incidence Rates of Early-Onset Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A496-A497
Author(s):  
Caitlin C Murphy ◽  
Piera M Cirillo ◽  
Nickilou Y Krigbaum ◽  
Barbara Cohn
Keyword(s):  
Early Pregnancy ◽  
Early Onset ◽  
In Utero ◽  
Incidence Rates ◽  
In Utero Exposure ◽  
Adult Offspring ◽  
Hydroxyprogesterone Caproate ◽  
Threatened Abortion ◽  
Risk Of Cancer ◽  
Early Onset Colorectal Cancer

Abstract Background: 17α-hydroxyprogesterone caproate (17-OHPC) is a synthetic progestogen introduced in the 1950s to treat habitual and threatened abortion in pregnant women. Although 17-OHPC is still available (tradename Makena), little is known about its effects on health of adult offspring, and questions concerning safety and effectiveness remain. For example, progestogens have been implicated in cancer, and trends in the use of 17-OHPC in early pregnancy during the 1950s and 60s parallel increasing incidence rates of certain cancers in young adults, such as early-onset colorectal cancer, born during that time. Methods: We examined the effect of 17-OHPC exposure in utero on risk of cancer in adult offspring in the Child Health and Development Studies, a cohort of women receiving prenatal care between June 1959 and September 1966, with deliveries through June 1967 (n=18,751 live births excluding neonatal deaths among 14,507 mothers). Diagnosed conditions and prescribed medications were abstracted from mothers’ medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received 17-OHPC (tradenames Delalutin and Proluton) in early pregnancy, defined as day 1 - 140 of gestation. Incident cancers diagnosed in offspring through 2018 were ascertained by linkage with the California Cancer Registry. Results: Among 18,751 live births, 954 cancers were diagnosed at ages 18 - 58 years. The most frequent cancers were breast (20.9%), cervical (10.9%), colorectal (7.1%), and prostate (5.9%) cancer and melanoma (9.2%). Although few mothers (n=181, 1.0%) received 17-OHPC in early pregnancy, in utero exposure was more common in offspring diagnosed with cancer (n=18, 1.9%) compared to those without cancer (n=163, 0.9%). Conditions indicating 17-OHPC included threatened abortion (54.0%), amnionitis (9.4%), and incompetent cervix (3.0%). 17-OHPC increased risk of any cancer in offspring (OR 2.08, 95% CI 1.27, 3.40), with particularly striking associations for colorectal (OR 4.78, 95% CI 1.49, 15.41) and prostate (OR 3.83, 95% CI 0.93, 15.83) cancer. There was no association between conditions indicating 17-OHPC and risk of any cancer in offspring (threatened abortion: n=1,891 mothers, OR 1.07, 95% CI 0.87, 1.32), or with use of other progestogens within 6 months prior to pregnancy (medroxyprogesterone acetate: n=50 mothers, OR 0.38, 95% CI 0.05, 2.76). Conclusions: Findings support susceptibility of multiple organ systems to endocrine disruption during early development and risk of cancer decades later - and may partly explain increasing rates of early-onset colorectal cancer. Even before mechanisms of carcinogenesis are elucidated, caution using 17-OHPC and other endocrine-active pharmaceuticals in early pregnancy is warranted, especially in the absence of a clear short-term benefit, and given the possible effect on risk of cancer in adult offspring.

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