Endocrine Delivery of Interferon-tau into the Uterine or Jugular Veins at Different Concentrations Protects the Corpus Luteum from Prostaglandin F2 Alpha Induced Luteolysis.

Abstract The corpus luteum (CL) is essential for maintenance of pregnancy in all mammals and luteal rescue, which occurs around day 16–19 in the cow, is necessary to maintain luteal progesterone production. Transcriptomic and proteomic profiling were performed to compare the day 17 bovine CL of the estrous cycle and pregnancy. Among mRNA and proteins measured, 140 differentially abundant mRNA and 24 differentially abundant proteins were identified. Pathway analysis was performed using four programs. Modulated pathways included T cell receptor signaling, vascular stability, cytokine signaling, and extracellular matrix remodeling. Two mRNA that were less in pregnancy were regulated by prostaglandin F2A in culture, while two mRNA that were greater in pregnancy were regulated by interferon tau. To identify mRNA that could be critical regulators of luteal fate, the mRNA that were differentially abundant during early pregnancy were compared to mRNA that were differentially abundant during luteal regression. Eight mRNA were common to both datasets, including mRNA related to regulation of steroidogenesis and gene transcription. A subset of differentially abundant mRNA and proteins, including those associated with extracellular matrix functions, were predicted targets of differentially abundant microRNA (miRNA). Integration of miRNA and protein data, using miRPath, revealed pathways such as extracellular matrix–receptor interactions, abundance of glutathione, and cellular metabolism and energy balance. Overall, this study has provided a comprehensive profile of molecular changes in the corpus luteum during maternal recognition of pregnancy and has indicated that some of these functions may be miRNA-regulated.

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Oxytocin-induced prostaglandin F2-alpha release is low in early bovine pregnancy but increases during the second month of pregnancy†

Biology of Reproduction ◽

10.1093/biolre/ioz169 ◽

2019 ◽

Author(s):

Jéssica N Drum ◽

Milo C Wiltbank ◽

Pedro L J Monteiro ◽

Alexandre B Prata ◽

Rodrigo S Gennari ◽

...

Keyword(s):

Corpus Luteum ◽

Early Pregnancy ◽

Artificial Insemination ◽

Peripheral Blood ◽

Prostaglandin F2α ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Interferon Stimulated Genes ◽

Prostaglandin F2 Alpha ◽

Oxytocin Receptors

Abstract Circulating prostaglandin F2α metabolite (PGFM) after an oxytocin challenge was evaluated throughout the first 2 months of pregnancy in lactating Holstein cows. On day 11, 18, and 25 after artificial insemination (AI), and on days 32, 39, 46, 53, and 60 of pregnancy, cows were challenged with 50 IU oxytocin, i.m. Blood was collected before (0 min), 30, 60, 90, and 120 min after oxytocin for plasma PGFM concentrations. Ultrasound evaluations were performed for pregnancy diagnosis on day 32–60 post-AI. Nonpregnant (NP) cows on day 18 were designated by a lack of interferon-stimulated genes in peripheral blood leukocytes and Pregnant (P) based on day 32 ultrasound. On day 11, P and NP were similar with low PGFM and no effect of oxytocin on PGFM. On day 18, oxytocin increased PGFM (3-fold) in NP with little change in P cows. Comparing only P cows from day 11 to 60, basal circulating PGFM increased as pregnancy progressed, with day 11 and 18, lower than all days from day 25 to 60 of pregnancy. Oxytocin-induced PGFM in P cows on day 25 was greater than P cows on day 18 (2.9-fold). However, oxytocin-induced PGFM was lower on day 25 compared to day 53 and 60, with intermediate values on day 32, 39, and 46 of pregnancy. Thus, the corpus luteum (CL) of early pregnancy (day 11, 18) is maintained by suppression of PGF, as reflected by suppressed PGFM in this study. However, during the second month of pregnancy, uterine PGF secretion was not suppressed since basal PGFM and oxytocin-induced PGFM secretion were elevated. Apparently, mechanisms other than suppression of oxytocin receptors maintain CL after day 25 of pregnancy.

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Hormonal regulation of prostaglandin F2 alpha receptor gene expression in mouse ovary

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.4.e686 ◽

1996 ◽

Vol 271 (4) ◽

pp. E686-E693

Author(s):

J. Sugatani ◽

Y. Masu ◽

M. Nishizawa ◽

K. Sakamoto ◽

T. Houtani ◽

...

Keyword(s):

Gene Expression ◽

Corpus Luteum ◽

Hormonal Regulation ◽

Receptor Gene ◽

Mrna Level ◽

Dependent Manner ◽

Mouse Ovary ◽

Receptor Mrna ◽

Prostaglandin F2 Alpha ◽

Receptor Gene Expression

In this study we examined regulation by pituitary gonadotropins of the prostaglandin F2 alpha (PGF2 alpha) receptor gene expression in the mouse ovary. Administration of pregnant mare serum gonadotropin (PMSG) to 35-day-old mice in the diestrus phase stimulated the ovary and enhanced the production of progesterone at 1 h PMSG also increased the ovarian PGF2 alpha receptor mRNA level in a time-dependent manner, reaching a sixfold maximum at 1 h. These actions of PMSG were mimicked by human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), and cholera toxin, all of which elevate intracellular adenosine 3',5'-cyclic monophosphate (cAMP). In situ hybridization revealed that PGF2 alpha receptor mRNA was localized to the corpus luteum, but the intensity of staining varied among corpora lutea in the same ovary. Exogenous PGF2 alpha inhibited the PMSG-stimulated progesterone production. These results demonstrate that gonadotropins may induce the expression of the PGF2 alpha receptor gene in luteal cells of the corpus luteum, probably by acting through a cAMP-mediated pathway, and that expression of the PGF2 alpha receptor may be functionally associated with the decrease in serum progesterone level.

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Possible role of interferon tau on the bovine corpus luteum and neutrophils during the early pregnancy

Reproduction ◽

10.1530/rep-15-0085 ◽

2015 ◽

Vol 150 (3) ◽

pp. 217-225 ◽

Cited By ~ 35

Author(s):

Koumei Shirasuna ◽

Haruka Matsumoto ◽

Shuichi Matsuyama ◽

Koji Kimura ◽

Heinrich Bollwein ◽

...

Keyword(s):

Corpus Luteum ◽

Neutrophil Migration ◽

Peripheral Circulation ◽

Interferon Tau ◽

Bovine Corpus Luteum ◽

Activated Neutrophils ◽

Endocrine Factor ◽

Uterine Environment ◽

And Function

When pregnancy is established, interferon tau (IFNT), a well-known pregnancy recognition signal in ruminants, is secreted by embryonic trophoblast cells and acts within the uterus to prepare for pregnancy. IFNT acts as an endocrine factor on the corpus luteum (CL) to induce refractory ability against the luteolytic action of PGF2α. Hypothesising that IFNT may influence not only the uterine environment but also the CL in cows via local or peripheral circulation, we investigated qualitative changes in the CL of pregnant cows during the maternal recognition period (day 16) and the CL of non-pregnant cows. The CL of pregnant animals had a higher number of neutrophils, and the expression of interleukin 8 (IL8) mRNA and its protein was higher as well as compared with the CL of non-pregnant animals. Although IFNT did not affect progesterone (P4) secretion and neutrophil migration directly, it stimulated IL8 mRNA expression on luteal cells (LCs), influencing the neutrophils, resulting in the increased migration of IFNT-activated neutrophils. Moreover, both IFNT-activated neutrophils and IL8 increased P4 secretion from LCs in vitro. Our novel finding was the increase in neutrophils and IL8 within the CL of pregnant cows, suggesting the involvement of IFNT function within the CL toward establishment of pregnancy in cows. The present results suggest that IFNT upregulates neutrophil numbers and function via IL8 on LCs in the CL of early pregnant cows and that both neutrophils and IL8, stimulated by IFNT, are associated with an increase in P4 concentrations during the maternal recognition period in cows.

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109 EFFECT OF SHORT TERM PROGESTERONE SUPPLEMENTATION ON CIRCULATING PROGESTERONE CONCENTRATION, CORPUS LUTEUM SIZE, AND EARLY EMBRYO DEVELOPMENT IN CATTLE

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab109 ◽

2013 ◽

Vol 25 (1) ◽

pp. 202

Author(s):

L. O'Hara ◽

N. Forde ◽

D. Rizos ◽

V. Maillo ◽

A. D. Ealy ◽

...

Keyword(s):

Corpus Luteum ◽

Early Embryo ◽

Negative Effects ◽

Short Term ◽

Concentration Data ◽

Interferon Tau ◽

Fluid Medium ◽

Conceptus Development ◽

Oviduct Fluid

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).

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