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PubMed1988

Effect of RU 486 on luteal function in the early pregnant rat.

A dose of 30 mg RU 486/kg, an antiprogesterone, was administered to pregnant rats on Day 2 (Group 1) or Day 4 (Group 2) of pregnancy. RU 486 significantly changed serum progesterone and oestradiol concentrations and luteal 3 beta-HSD and 20 alpha-HSD activities in Group 1, and implantation was significantly inhibited. The luteal 3 beta-HSD activity in Group 2 rats on Day 6 was significantly (P less than 0.01) lower than the control value (7.5 +/- 0.6 and 10.1 +/- 0.6 mU/mg protein respectively). This decline in the 3 beta-HSD activity was followed by a marked decrease in the serum progesterone concentration, resulting in a significant decrease of the progesterone/oestradiol ratio and implantation was completely inhibited. The 20 alpha-HSD activity, which could not be detected on Day 6 in the control rats, was twice as great in Group 2 than in Group 1 rats (17.5 +/- 1.2 and 7.4 +/- 3.1 mU/mg protein respectively). Ultrastructural examination of corpora lutea of Group 2 rats confirmed luteolysis. These results suggest that RU 486 has a luteolytic effect and its anti-implantation effect is concomitant with luteolysis of the corpora lutea of pregnancy.

20-Hydroxysteroid Dehydrogenases↗
PubMed1985

Release of progesterone by porcine luteal cells from different days of estrous cycle: effect of LH, PRL and PGF2 alpha.

The secretion of progesterone (P4) by porcine luteal cells from 5th, 8th, 14-16th and 17th day of estrous cycle was estimated under basal conditions and after stimulation with LH (0.1 and 1 microgram ml-1), PRL (2 micrograms ml-1) and PGF2 alpha (0.1 and 5 micrograms ml-1). P4 in the medium was estimated by radio-immunological method after 30 min and then after 3, 6, 9 and 15 h of incubation. Luteal cells from 5th, 8th, 13th, 14-16th and 17th day of estrous cycle released on average 140.9 +/- 14.4, 138.9 +/- 12.7, 224.4 +/- 21.3, 62.3 +/- 4.2 ng and 6.4 +/- 0.6 ng P4 per ml-1 medium, respectively. Luteal cells from 5th day of the estrous cycle significantly increased (P less than 0.05) P4 release during first 30 min of incubation in the presence both doses of LH, but the dose of 1 microgram LH significantly stimulated P4 secretion during next 3 h, too. Only the luteal cells from 13th day of the estrous cycle increased (P less than 0.05) P4 production in the presence of 1 microgram LH, and prolactin exerted luteolytic effect also only on luteal cells from 13th day of the estrous cycle. The release of P4 by luteal cells from 5th day of the estrous cycle increased (P less than 0.05) during first 30 min of incubation in the presence of PGF2 alpha. However, PGF2 alpha (5 micrograms) exerted inhibitory effect (P less than 0.05) on P4 release by luteal cells from only 13th day of the estrous cycle. The results showed that the effect of these hormones on P4 secretion by luteal cells depended on the period of estrous cycle and doses used.

Animals↗
PubMed1988

Effects of gonadotrophin-releasing hormone and prostaglandin F-2 alpha on corpus luteum function and timing of the subsequent ovulation in the mare.

Standard bred mares that were cycling normally were treated beginning on Days 9 or 10 of the oestrous cycle with repeated pulses of GnRH (20 micrograms/h) and/or a single injection of prostaglandin (PG)F-2 alpha (alfaprostol, 3 mg), and were subsequently bled and palpated daily until the next ovulation. GnRH treatment increased serum concentrations of LH and progesterone at 4 days after the start of treatment compared to controls. The combination of PGF-2 alpha + GnRH treatment resulted in an immediate decline in serum progesterone values, and subsequently decreased the interval to next ovulation by 4.5 days compared to controls. Mean serum concentrations of FSH were not different among treatment groups 4 days after the start of treatment, and there was a consistent trend among all treatment groups for decreasing concentrations of FSH within the 6 days before ovulation. We conclude that, under our experimental conditions, pulsatile administration of GnRH provides a short-term luteotrophic stimulus, probably by the elevation in serum LH, but that this stimulus cannot indefinitely prevent the luteolytic effects of exogenously administered PGF-2 alpha. Although GnRH treatment combined with PGF-2 alpha injection hastened the impending ovulation, this regimen was no more effective than PGF-2 alpha treatment alone.

Animals↗
PubMed1987

Indomethacin treatment prevents prolactin-induced luteolysis in the rat.

Adult female rats were hypophysectomized and their pituitary glands autotransplanted beneath the left kidney capsule on day 2 (day 1 was the day of ovulation). In such rats the pituitary secretes prolactin fairly constantly and the corpora lutea secrete progesterone for several months. To induce the luteolytic effect of prolactin the rats were first injected s.c. with 2-bromo-alpha-ergocryptine (CB-154) on cycle days 12, 13 and 14 (i.e. 10, 11 and 12 days after operation) to depress prolactin secretion, and then with CB-154 vehicle (70% ethanol) daily until cycle day 21, to allow prolactin secretion to resume. One ovary was removed from each rat on day 15 and the remaining one on day 22. The mean (+/- S.E.M.) weight of the corpora lutea on day 15 was 1.46 +/- 0.06 mg and 0.98 +/- 0.07 mg on day 22 (n = 17). In contrast, rats in which the CB-154 treatment was maintained to day 21 had corpora lutea which weighed 1.31 +/- 0.09 on day 15 and 1.47 +/- 0.08 mg on day 22 (n = 15). To investigate whether indomethacin, a prostaglandin synthesis inhibitor, affected the luteolytic action of prolactin, the experiment was repeated, but on day 15 (after the removal of one ovary) the groups in which CB-154 treatment was stopped, as well as the group in which CB-154 treatment was maintained, were each divided into two groups. In one, indomethacin-containing silicone elastomer wafers and, in the other, blank silicone elastomer wafers, were placed within the bursa of the remaining ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Localization of prostaglandin F2 alpha inhibition of lipoprotein use by bovine luteal cells.

Prostaglandin F2 alpha (PGF2 alpha) inhibits lipoprotein-stimulated progesterone production by bovine luteal cells in vitro and the objective of this study was to localize the site of action of PGF2 alpha. Cultured bovine luteal cells were treated with PGF2 alpha for seven days, and then with either lipoproteins or 25-hydroxycholesterol in the presence of aminoglutethimide (which inhibits cholesterol side-chain cleavage) for the final 48 h. The effects of PGF2 alpha on progesterone production, cellular cholesterol content, mitochondrial cholesterol content and cholesterol side-chain cleavage activity were determined. As expected, PGF2 alpha inhibited (P less than 0.05) lipoprotein-stimulated progesterone production. However, PGF2 alpha did not inhibit low-density lipoprotein-stimulated, or high density lipoprotein-stimulated, increases in cellular cholesterol (P less than 0.05) or inhibit lipoprotein-induced increases in mitochondrial cholesterol content (P less than 0.05). Additionally, cholesterol content of mitochondria increased (P less than 0.05) in the presence of PGF2 alpha alone. To determine if the PGF2 alpha-induced inhibition of steroidogenesis occurred at, or after, the side-chain cleavage reaction, we treated cells with the readily diffusable sterol, 25-hydroxycholesterol. Prostaglandin F2 alpha did not inhibit 25-hydroxycholesterol-stimulated progesterone production (P less than 0.05). Prostaglandin F2 alpha may therefore exert its luteolytic effect at a site after cholesterol transport to the mitochondria but before cholesterol side-chain cleavage.

Aminoglutethimide↗
PubMed1994

Effects of oestrogen on progesterone synthesis and arachidonic acid metabolism in human luteal cells.

OBJECTIVE: Locally produced oestrogens and prostaglandins (PGs) are implicated in the regulation of luteal lifespan in the human ovary. This study (1) assesses direct effects of these factors on progesterone synthesis in isolated luteal cells, and (2) explores interactions between luteal age and treatment with gonadotrophin or oestrogen on the metabolism of arachidonic acid (prostaglandin precursor) by steroidogenic luteal cells in vitro. DESIGN: Primary monolayer cultures of human luteal cells obtained at different stages of the luteal phase were used to investigate the effect of oestradiol, catechol oestrogens (2- and 4-hydroxyoestradiol), diethylstilboestrol, PGE2 and PGF2 alpha on basal and human chorionic gonadotrophin (hCG) stimulated progesterone production in vitro. The role of PGs as modulators of luteal cell function was further investigated by studying the metabolic fate of radioactively labelled arachidonic acid in hormone treated (oestradiol and hCG) and control cultures, assessed by high performance liquid chromatography. PATIENTS: Corpora lutea were enucleated from nine women with regular ovulatory cycles undergoing microsurgical reversal of tubal sterilization. Granulosa cell aspirates were obtained from three patients undergoing in-vitro fertilization treatment. RESULTS: PGE2 and PGF2 alpha at various concentrations did not have a consistent effect, whereas oestradiol, diethylstilboestrol (and 2-hydroxyoestradiol in early luteal cell cultures) significantly inhibited basal and hCG stimulated progesterone biosynthesis. Evidence for direct inhibition of 3 beta-hydroxysteroid dehydrogenase enzymic activity by oestradiol was obtained. Both major metabolic pathways of arachidonic acid (lipoxygenase and cyclo-oxygenase) were operative in steroidogenic luteal cells recovered throughout the luteal phase. The ratio of PGE2 to PGF2 alpha synthesis in vitro by human luteal cells from endogenously incorporated arachidonic acid did not change significantly with corpus luteum age, with PGE2 tending to predominate. Oestradiol treatment shifted arachidonic acid metabolism from the lipoxygenase towards the cyclooxygenase pathway in cells isolated from ageing corpora lutea. CONCLUSIONS: Oestradiol, at relatively high concentrations, is a potent inhibitor of basal and hCG induced luteal cell steroidogenesis in vitro. No support is provided for the concept that luteolysis is mediated by local production of PGF2 alpha. The putative luteolytic effect of oestradiol may entail reduced metabolism of arachidonic acid to lipoxygenase derived products by luteal cells rather than direct stimulation of prostaglandin production by itself.

Arachidonic Acids↗
PubMed1988

Rat placental luteotropin: initial secretion and luteolytic quality.

The secretion of placental lactogen begins early in pregnancy. Previous studies indicate that rat placental lactogen (rPL) is secreted from Day 8 of pregnancy and that it is luteolytic as well as luteotrophic. This study establishes the onset of both the luteotrophic and the luteolytic effects of placental lactogen in pregnant rats subject to timed hypophysectomy. Pregnancy was preserved in all groups with the administration of dydrogesterone (9 beta, 10 alpha-pregna4,6-diene-3, 20 dione), a progesterone analog, and diethylstilbestrol, an estrogen analog. Plasma progesterone and 20 alpha-hydroxypregn-4-ene-3-one (20-OHP) were measured in serial serum samples by RIA. The data indicate that rPL is secreted as early in pregnancy as the seventh day. Rats hypophysectomized on Day 6 of pregnancy or later had ovaries that contained corpora lutea that secreted increasing quantities of progesterone during pregnancy. On Day 16 serum progesterone values were lowest in animals operated on Days 4 and 5 compared to animals operated on Days 6 or 8. The 20-OHP serum values from animals operated on Days 4 and 5 declined steadily from Day 8 to Day 16. These findings indicate progestational incompetency, which was confirmed morphologically. Thus, rPL secretion begins by Day 7 and it is both luteotrophic and luteolytic.

20-alpha-Dihydroprogesterone↗
PubMed2004

Endocrine secretion of prostaglandin F2alpha in cyclic gilts is decreased by intrauterine administration of exogenous oxytocin.

When administered systemically, oxytocin (OT) stimulates secretion of uterine prostaglandin F2alpha (PGF2alpha) in swine, but the role of endometrially-derived OT in control of PGF2alpha release is not clear. This study determined the effect of exogenous OT, administered into the uterine lumen of intact cyclic gilts, on PGF2alpha secretion during late diestrus. Intrauterine infusion of 40USP units OT (in 30 ml 0.9% saline) was performed for 30 min (1 ml/min) into each uterine horn between 7:00 and 9:00 h on days 10, 12, 14 and 16 after estrus. Beginning 20 min before infusion, samples of jugular venous blood were drawn at 5-10-min intervals for 140 min for quantification of 13,14-dihydro-15-keto-PGF2alpha (PGFM), the major stable metabolite of PGF2alpha. Progesterone was analyzed in samples collected 0, 60 and 120 min after initiation of OT infusion. Treatment with OT did not alter plasma concentrations of PGFM on days 10 or 12 but decreased (P<0.001) PGFM concentrations for 40 min after onset of infusion on day 16. Concentrations of PGFM also were reduced in the pre-treatment samples on day 14 (P=0.05) and day 16 (P<0.001) in OT-infused gilts. Plasma progesterone declined (P<0.01) between days 10 and 16 in control-infused gilts but did not decline until after day 14 (P<0.001) in gilts infused with OT. These results indicate that when OT is administered into the uterine lumen of pigs during late diestrus, it has an anti-luteolytic effect to reduce endocrine secretion of PGF2alpha and delay the decline in progesterone that occurs during luteolysis.

Animals↗
PubMed1987

Acute decrease in progesterone and increase in estrogen secretion caused by relaxin during late pregnancy in beef heifers.

Purified porcine relaxin (3000 U/mg) was administered im (RLX-IM; 1 mg; n = 2) and in the cervical os (RLX-OS; 1 mg; n = 2) on day 273 (approximately 10 days before parturition normally occurs) of gestation to determine the profiles of immunoreactive relaxin and its effects on progesterone, estrone (E1), and 17 beta-estradiol (17 beta-E2) secretion in peripheral blood plasma of beef heifers. Controls received either 0.01 M PBS (1 ml, im; n = 2) or 0.01 M gel-PBS (gel; 1 ml, os; n = 2) in cervical os. One relaxin-treated (im) heifer calved at 4 h and 36 min after treatment; thus, data from this heifer were not included in subsequent analysis. Relaxin-treated heifers showed an acute elevation in relaxin, a precipitous decrease in progesterone, and a significant (P less than 0.05) elevation of E1 and 17 beta-E2. Plasma relaxin levels were 4.95, 1.5, and 0.24 ng/ml at 0.5 h in RLX-IM, RLX-OS, and control animals, respectively. Peripheral plasma relaxin peaked between 23-31 ng/ml 1-2.5 h before returning to less than 0.5 ng/ml 5-12 h after treatment. Relaxin administration accounted for 70%, 73%, and 58% of the progesterone, E1, and 17 beta-E2 variability between treatments, respectively. An abrupt decrease (P less than 0.01) in progesterone preceded the rises (P less than 0.05) in E1 and 17 beta-E2 at 1.5, 2-2.5, and 2-3.5 h, respectively. Maximum progesterone deviations from the pretreatment mean concentration were -5.43, -3.05, and -0.92 ng/ml for RLX-IM, RLX-OS, and controls. Progesterone rebounded from 36% to 61% and 62% to 79% of respective pretreatment means for RLX-IM and RLX-OS. Peak elevation of E1 was 407.3, 306.5, and 71.5 pg/ml and that of 17 beta-E2 was 82.2, 35.8, and 7.8 ng/ml for RLX-IM, RLX-OS, and controls, respectively. These results provide strong evidence that a pharmacological dosage of relaxin induces an acute depression of progesterone secretion beginning within 90 min in beef heifers during late pregnancy. We suggest that these early and marked luteolytic effects of relaxin on progesterone secretion in cattle could be by direct or indirect actions via mechanisms that are yet unknown.

Animals↗
PubMed1979

Termination of pregnancy in the rat by RMI 12,936.

Administration of a steroid RMI 12,936 (2 MG) ON DAY 8 OF PREGNANCY RESULted in an interruption of gestation within 5 days. No significant changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and pregnenolone (delta 5P) were recorded during the course of termination of pregnancy by RMI 12,936. However, a significant rise in serum delta 4P and hypertropic corpora lutea were evident on day 13 of pregnancy when all treated females showed dead conceptus. The placental tissue was still present at the time of pregnancy termination. On the other hand, serum LH levels was significantly suppressed 24 hr after the treatment and maintained at a very low level. The reduction of LH might be due to a lowered hypophyseal sensitivity towards LH-RH. The occurrence of in utero dead fetus without interference of delta 4P production suggests that in the rat RMI 12,936-induced termination of pregnancy is due to its embryotoxic rather than luteolytic effect. Although the treated females did not return to normal estrous cycles for a period of 2 weeks after pregnancy termination, they were sexually receptive. Successful mating resulted in normal pregnancy which occurred 30-35 days after RMI 12,936 treatment.

Abortifacient Agents↗
PubMed1981

Luteolysis in the hamster: abrogation by gonadotropin and prolactin pretreatment.

The luteolysis which terminated pseudopregnancy (PSP) in superovulated hamsters was studied. Spontaneous luteolysis occurred before 1100 on Day 7 of PSP and was characterized by a rapid decline in circulating progesterone levels. Luteolysis induced by prostaglandin F2 alpha (PGF2 alpha) on Day 5 of PSP displayed a similar rapid reduction in progesterone over 24 hours. In both cases levels of the progesterone metabolite 20 alpha hydroxypregn-4-ene-3-one (20 alpha-OHP) were less than 2 percent of progesterone levels and declined in a manner similar to progesterone. This suggests that conversion of progesterone or its precursors to 20 alpha-OHP was not a functional aspect of luteolysis in the hamster. Pretreatment with either prolactin (PRL), luteinizing hormone (LH) or follicle stimulating hormone (FSH) failed to prevent PGF2 alpha-induced luteolysis on Day 5 in the superovulated PSP hamster. Combinations of PRL and LH, LH and FSH or PRL and FSH were also unsuccessful in abrogating luteolysis. However, pretreatment with a combination of PRL, FSH and LH prevented luteolysis in 11/14 animals. These results suggest that luteotropic agents can reverse the luteolytic effects of PGF2 alpha in the hamster.

20-alpha-Dihydroprogesterone↗
PubMed1982

Plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F(2alpha) and progesterone during oxytocin-induced oestrus in the goat.

Fertile oestrus was induced in dairy goats by sub-cutaneous administration of 100 i.u. oxytocin per day between days 3-6 of the oestrous cycle. Peripheral plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM), the major metabolite of prostaglandin (PG) F(2alpha), were elevated significantly (P<0.001), relative to controls, 30 minutes after oxytocin with peak values of between 300-800 pg ml(-1). Unlike control animals, plasma progesterone concentrations did not rise in the oxytocin-treated group after day 4. These results lend support to the hypothesis that the luteolytic effect of oxytocin in goats may be mediated via uterine PG production.

Journal Article↗
PubMed1983

Prevention of the luteolytic action of oxytocin in the goat by inhibition of prostaglandin synthesis.

Oxytocin-induced luteolysis in goats was associated with significant increases in peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Oral administration of the prostaglandin (PG) synthetase inhibitor meclofenamic acid (l g/day) prevented both the luteolytic action of oxytocin and the increase in PGFM concentrations. These results confirm that the luteolytic effect of oxytocin is mediated via the production and release of PGF2alpha.

Journal Article↗
PubMed1987

Plasma concentration of progesterone during normal estrous cycles and following prostaglandin F(2alpha) treatment of Bos indicus and tropic-adapted Bos taurus heifers.

The introduction of the use of prostaglandin F(2alpha) (PGF(2alpha)) to synchronize estrus in cattle adapted to the tropics suggests a need to investigate the endocrine response to this treatment. Progesterone (P) concentrations in blood plasma of Bos indicus and tropic-adapted Bos taurus heifers during normal estrous cycles and following estrus synchronization were compared. After PGF(2alpha) administration, the heifers were divided into two groups on the basis of response to treatment. Mean P levels in heifers showing estrus after the first injection ranged from 1.0-3.0 ng/ml, decreasing to 0.2-0.4 ng/ml 24 to 48 hr after treatment. The second group exhibited estrus only after the second PGF(2alpha) injection and had low P (0.2-0.9 ng/ml) in plasma before the first injection. Mean peak P levels in both groups 8 to 12 d after the first injection in the periestrous period were not different from values in the same heifers at similar periods of the preceding control estrous cycle. Neither the tropical location nor breed affected the luteolytic effect of PGF(2alpha).

Journal Article↗
PubMed2005

Blood flow: a key regulatory component of corpus luteum function in the cow.

Prostaglandin F2alpha (PGF2alpha) is the primary luteolysin in the cow. During the early luteal phase, the corpus luteum (CL) is resistant to the luteolytic effect of PGF2alpha. Once mature, the CL becomes responsive to PGF2alpha and undergoes luteal regression. These actions of PGF2alpha coincide with changes in luteal blood flow (BF): PGF2alpha has no effect on BF in the early CL, but acutely increases BF in the peripheral vasculature of the mature CL within 30 min of PGF2alpha injection. During spontaneous luteolysis, luteal BF increases on Days 17-18 of the estrous cycle, prior to any decrease in plasma progesterone (P). The increase in luteal BF is synchronous with an increase in plasma PGFM levels, suggesting that pulsatile release of PGF2alpha from uterus stimulates the increase in luteal BF. Serial biopsies of these CL showed that mRNA expression for endothelial nitric oxide synthase (eNOS) together with endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) increases on Days 17-18 when the luteal BF is elevated. On Day 19 when plasma P level firstly decreases, eNOS mRNA returns to the basal level whereas ET-1 and ACE mRNA remains elevated. Cyclooxygenase-2 (COX-2) mRNA expression increases on Day 19. In support of these data, an in vivo microdialysis study revealed that luteal ET-1 and angiotensin II (Ang II) secretion increases and precedes PGF2alpha secretion during spontaneous luteolysis. In conclusion, we show for the first time that an acute increase of BF occurs in the peripheral vasculature of the mature CL together with increases in eNOS expression and ET-1 and Ang II secretion in the CL during the early stages of luteolysis in the cow. We propose that the increase in luteal BF may be induced by NO from large arterioles surrounding the CL, and simultaneously uterine or exogenous PGF2alpha directly increases ET-1 and Ang II secretion from endothelial cells of microcapillary vessels within the CL, thereby suppressing P secretion by luteal cells. Taken together, our results indicate that an acute increase in luteal BF occurs as a first step of luteolysis in response to PGF2alpha. Therefore, local BF plays a key role to initiate luteal regression in the cow.

Angiotensin II↗
PubMed1985

Luteal phase variations in endogenous concentrations of prostaglandins PGE and PGF and in the capacity for their in vitro formation in the human corpus luteum.

One evidence for a luteolytic role for prostaglandin F2 alpha in the human is the increase in luteal PGF at times corresponding to luteolysis as reported earlier by us and other groups. There have been other contradictory reports on this point. In the present experiments we have measured the concentrations of PGE and PGF in 16 more human corpora lutea and have determined the capacity of those tissues to form PGE and PGF in vitro. PGF concentrations were highest in the mid luteal phase but were accompanied by high PGE concentrations. On the other hand, in the late luteal phase PGF concentrations, lower than in mid luteal but generally higher than in early luteal phase, were significantly higher than PGE concentrations. This pattern in PGE and PGF concentrations was also evident in the capacity of these tissues to form these compounds in vitro. In view of the known capacity of PGE2 to counteract the luteolytic effect of PGF2 alpha, these variations in the relative concentrations of PGE and PGF during the luteal phase may be of significance in the process of luteolysis in the human.

Corpus Luteum↗
PubMed1997

Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-tau and other cytokines in early pregnancy.

This review considers the potential reduction of embryo mortality in vitro and in vivo in ruminants. Data on cytokines provided by different fields of reproductive immunology and biology were collated. Because of the crucial importance of the local interactions between the embryo and its dam, the expression of growth-factor and cytokine genes was analysed in the embryo proper, trophoblast, oviduct and endometrium by reverse transcriptase polymerase chain reaction in sheep and in cattle during the pre- and periimplantation periods. Many deleterious cytokines, such as tumour necrosis factor-alpha, interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth factor-beta, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1), granulocyte-macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-tau appeared to be involved in embryo survival in ruminants and other species. Their administration is efficient in a murine experimental model (CBA/J x DBA/2) of embryonic and fetal mortality. For instance, recombinant ovine IFN-tau (roIFN-tau) injected at the moment of implantation drastically reduces embryonic mortality in this model. In ruminants, roIFN-tau and recombinant bovine IFN-tau are very efficient in maintaining progesterone luteal secretion in cyclic animals. The involvement of IFN-tau in the mechanisms of maternal pregnancy recognition are particularly detailed in relation to inhibition of 13,14 dihydro-15-keto-prostaglandin F2 alpha (PGFM) pulses and oxytocin uterine receptivity. A synthetic model of the anti-luteolytic effects of IFN-tau on the endometrial cell is proposed. Finally, the particular potential of serum pregnancy-specific proteins (PSPs: PSPB, PSP60, pregnancy-associated glycoprotein) for monitoring embryo survival, with examples given for cattle and sheep is underlined.

Amino Acid Sequence↗
PubMed1989

Establishment of pregnancy in sheep and pigs.

Sheep conceptuses secrete a protein, ovine trophoblast protein-1 (oTP-1), between days 10 and 21 of gestation, that is responsible for establishment of pregnancy. oTP-1 inhibits uterine production of episodic release of prostaglandin (PG) F2 alpha (PGF) necessary for luteolysis and produced in response to oestradiol and oxytocin. oTP-1 does not compete with oxytocin for binding to its receptors or interfere with oxytocin stimulation of the inositol phospholipid second messenger system after oxytocin receptors are formed. However, oTP-1 may affect synthesis of oxytocin, oestrogen and/or progesterone receptors to alter the ability of the uterus to produce episodic pulses of PGF in response to episodic pulses of oxytocin. Porcine conceptuses secrete oestrogens between days 10 and 15 of pregnancy that are essential for establishment of pregnancy. Oestrogens, directly or indirectly, alter secretion of PGF from an endocrine direction (toward the uterine vasculature) to an exocrine direction (toward the uterine lumen). PGF sequestered in the uterine lumen is unavailable to exert a luteolytic effect on the corpus luteum (CL). Pig conceptus secretory proteins stimulate uterine production of PGF and PGE, but do not appear to be responsible for inhibition of luteolysis. Conceptus secretory proteins of sheep and pigs include proteins that have antiviral activity and are considered interferons. In sheep, oTP-1 has antiluteolytic, immunosuppressive, antiviral and possibly antiproliferative properties. The specific pig conceptus secretory protein(s) possessing antiviral activity has not been established. Unlike oTP-1, however, pig interferon-like protein(s) does not appear to possess antiluteolytic activity.

Animals↗