Oxytocin Receptor Concentrations Research Articles

Social dysfunction in the neurodevelopmental model of schizophrenia in male and female rats: Behavioural and biochemical studies

Social dysfunction is among the core symptoms of schizophrenia. The neuropeptides oxytocin (OXT) and vasopressin (VP) are involved in the regulation of social behaviour and social cognition. There are indications that both of these neurotransmitter systems are altered in schizophrenia. Prenatal (embryonic day 17) exposure to the neurotoxin methylazoxymethanol acetate (MAM; 22 mg/kg) leads to a schizophrenia-like phenotype in rats and has been used as a model of schizophrenia symptoms. Here, we examined the social phenotype of MAM-exposed female and male rats and measured concentrations of OXT, VP and their specific receptors in various brain areas involved in the control of social behaviour.We report decreases in social behaviour and ultrasonic vocalisations (USVs) in the MAM rats during social encounters. Specifically, the duration of social interactions and number of corresponding USVs were reduced in this group. In the MAM rats, “positive” 50-kHz USVs were flatter, i.e., displayed lower bandwidth, a greater percentage of “short” calls and lower percentage of frequency-modulated calls. The MAM animals exhibited diminished interest towards social stimuli in olfactory preference tests. In the resident-intruder test, MAM exposure reduced dominance behaviour only in the males. We also report cognitive impairments, including reduced novel object recognition and cognitive inflexibility in the attentional set shifting test, and decreased OXT and OXT receptor concentrations in the prefrontal cortex and hypothalamus and VP and VP receptors in the hypothalamus in the MAM rats.Deficits in central OXT and VP systems may underlie abnormalities present in the MAM model of schizophrenia.

Molecular biology of trophoblast interferons and studies of their effects in vivo

Southern blotting of bovine genomic DNA indicated the presence of at least 3 bovine tIFN genes. The full DNA sequence of one of these genes, thought to be expressed in trophoblast, has been determined, including 193 bp of 5' non-coding region. The inferred amino acid sequence of bovine tIFN is more similar to ovine tIFN (80%) than to bovine IFN-alpha II (70%). The 5' flanking sequence has some similarity with bovine IFN-alpha II, and may contain a viral response element. A recombinant bovine alpha I interferon (Ciba Geigy; brIFN), resembling tIFN, extended oestrous cycle length in sheep when administered by intrauterine infusion over the period, Days 12-15 after oestrus, when maternal recognition of pregnancy occurs. Intramuscular injection was only effective at the doses used if given over a longer period (i.e. Days 9-15). Our experiments indicate that both tIFN and brIFN inhibit luteolysis by preventing a rise in endometrial oxytocin receptor concentrations, and suggest that tIFN achieves this by extending the time for which progesterone suppresses oxytocin receptor development. Further studies are required to confirm this hypothesis and to elucidate the interaction of the effects of progesterone and tIFN in endometrial cells.

Oxytocin receptors in dioestrous and anoestrous canine uteri.

The aim of the study was to localize oxytocin receptors (OTR) and measure mRNA expression of OTR in the canine uterus with and without the influence of progesterone. Uterine samples were taken from nine anoestrous and eight dioestrous bitches during ovariohysterectomy. Histological changes were evaluated in haematoxylin and eosin (HE)-stained samples. Purified polyclonal antibody for OTR was used in immunohistochemistry to localize receptors in uterine layers. Relative mRNA concentration of OTR was evaluated with real-time PCR from full-thickness uterine samples taken from the middle horn and the body. Myometrial smooth muscle cells, endometrial luminal epithelium (LE) and deep and superficial glandular epithelium were positively stained for oxytocin receptors in non-pregnant animals. No significant difference in staining intensity was detected between uterine middle horn and body. However, the staining intensity of LE was significantly higher in dioestrous than in anoestrous uteri (p<.05). Leucocytes and endothelium of blood vessels were also positively stained for OTR. Real-time PCR showed no significant differences in OTR mRNA expression between the middle horn and the body of the uterus, or between anoestrous and dioestrous uterus. No correlation was noted between OTR mRNA expression and blood progesterone concentration. In conclusion, despite the apparent inactivity, the uterus of the non-pregnant bitch expresses OTR. The distribution or relative expression of OTR does not differ between uterine horn and body in dioestrus or anoestrus except in LE. LE may have more oxytocin-dependent activity during dioestrus than anoestrus.

Differently shaped spines increase in the posterodorsal medial amygdala of oxytocin knockout female mice

The posterodorsal medial amygdala (MePD) is a sexually dimorphic area in the social behavior neural network, with high concentration of oxytocin (OT) receptors. Wild type (WT) and OT knockout (OTKO) females were studied in proestrus, and Golgi-impregnated spines in the MePD were classified. Results show that the OTKO group has increased density of thin, mushroom, and stubby/wide spines when compared to the WT (p<0.01 in all cases). These data indicate that OT is an important synaptic modulator in the MePD, a finding that is likely involved with the display of the female sexual behavior.

Effect of Administration of Oxytocin During Diestrus on Corpus Luteum Function and Endometrial Oxytocin Receptor Concentration in Cycling Mares

The objectives of this study were to (1) compare the effect of twice versus once daily administration of oxytocin on days 7-14 after ovulation on the duration of corpus luteum (CL) function and (2) determine the effect of oxytocin treatment on endometrial oxytocin receptor concentration in mares. In experiment 1, mares were randomly assigned to three groups on day 7: (1) untreated control group (n = 7), (2) twice daily oxytocin treatment group (n = 7), and (3) once daily oxytocin treatment group (n = 8). Oxytocin-treated mares received 60 U of oxytocin intramuscularly (IM) the respective number of times each day on days 7 through 14. One of seven control mares (14%), five of seven (71%) twice daily oxytocin-treated mares, and five of eight (63%) once daily oxytocin-treated mares had prolonged CL function. There was no significant difference in the proportion of mares with prolonged CL function between the two oxytocin-treated groups, and collectively, oxytocin treatment increased (P < .05) the proportion of mares with prolonged CL function compared with no treatment. In experiment 2, mares were randomly assigned to two groups (n = 5/group): (1) saline-treated control mares, and (2) oxytocin-treated mares. Beginning on day 7, control mares received 3 mL of sterile saline IM twice daily, and oxytocin-treated mares received 60 U of oxytocin IM twice daily through day 14. On day 15, endometrial oxytocin-binding capacity was determined (as a measure of oxytocin receptor concentration), and there was no difference (P > .1) between control and oxytocin-treated mares (1,465.7 ± 108 and 1,382.8 ± 108 fmol/mg protein [mean ± standard error of mean], respectively).

Characterization of the Cyclic Adenosine Monophosphate Target Site in the Oxytocin Receptor Gene in Rabbit Amnion1

Oxytocin (OXT) is a potent stimulator of prostaglandin E(2) (PGE(2)) synthesis by rabbit amnion cells obtained near the end of pregnancy. Coincident with a marked increase in sensitivity of PGE(2) synthesis to OXT, the concentration of OXT receptors (OXTRs) is abruptly upregulated about 200-fold at term. This increase can be mimicked in preterm amnion cells in primary culture by the synergistic action of agents that increase cAMP synthesis and by glucocorticoids. To elucidate the mechanism of cAMP action, we cloned the rabbit OXTR gene and isolated a 200-base pair (bp) forskolin-responsive region about 4.7 kilobase upstream from the transcriptional start site using transient transfection assays. This region corresponds to a DNase I-hypersensitive site that appears in amnion tissue only near the end of pregnancy, when OXTRs are upregulated. The effects of forskolin were mediated in part by cAMP response element binding protein (CREB), as coexpression of reporter constructs with dominant negative CREB inhibited reporter expression. In addition, CREB was cross-linked to sites in the 200-bp region only in chromatin isolated from cells near the end of pregnancy, as demonstrated by chromatin immunoprecipitation (ChIP). Because the transient transfection results are consistent with work using tissue extracts (DNase I hypersensitivity and ChIP), we conclude that cAMP, acting through a specific upstream CREB binding site, is critical for the physiological upregulation of OXTRs in the amnion at the end of gestation.

Fecal and Urinary Lignans, Intrafollicular Estradiol, and Endometrial Receptors in Lactating Dairy Cows Fed Diets Supplemented with Hydrogenated Animal Fat, Flaxseed or Sunflower Seed

We hypothesized that the inclusion of flaxseed in the diets of lactating dairy cows will increase urinary and fecal concentrations of the lignans, secoisolariciresinol diglycoside (SDG), enterolactone and enterodiol, reduce intrafollicular concentrations of IGF-I and estradiol, and subsequently reduce estradiol and oxytocin receptor expression in the endometrium. To test this hypothesis, 27 cycling, lactating Holstein cows were assigned to 1 of 3 diets supplemented with saturated fatty acids (SAT), flax (FLX), or sunflower (SUN) seed. Rations were formulated to provide 750 g supplemental fat/cow/d in all dietary groups. Ovulation (Day 0) was synchronized, and 5 d later, follicles>8 mm were ablated by an ultrasound-guided procedure in all cows. Samples of blood (Days 0 to 14), follicular fluid (Day 5 and 15), endometrium (Day 15), as well as urine and feces were collected in a subset of the animals. The fecal concentrations of SDG and enterodiol were higher (P<0.05) in cows fed FLX than in those fed SAT or SUN. Enterodiol increased (P<0.05) in urine samples of cows fed FLX, compared to those of cows fed SUN. However, follicular estradiol concentrations on Day 5 and 15 and endometrial concentrations of estradiol and oxytocin receptors on Day 15 did not differ among the dietary groups. Mean plasma progesterone concentrations were higher (P<0.05) in cows fed FLX and SUN than in those fed SAT. In summary, a diet supplemented with flaxseed increased the concentrations of SDG and enterodiol in feces, as hypothesized, but did not alter intrafollicular concentrations of IGF-I or estradiol, or endometrial populations of oxytocin or estrogen receptors in lactating dairy cows.

Progesterone metabolism in bovine endometrial cells and the effect of metabolites on the responsiveness of the cells to OT-stimulation of PGF 2α

Oxytocin receptor (OTR) expression is suppressed by progesterone (P4) during the luteal phase of the estrous cycle and then it increases at the time of luteolysis, but its regulation is still not completely understood. The objective of this work was to characterize P4 metabolism by endometrial cells in vitro and determine if metabolites were able to modify prostaglandin secretion in response to oxytocin (OT). Endometrial epithelial and stromal cells were incubated with 3H-P4 or 3H-pregnenolone (P5) for 6 or 24 h. Metabolites in the medium were separated by HPLC. The results showed that P4 and P5 were converted to two major polar metabolites and a less polar metabolite that was identified as 5α- or 5β-pregnanedione by LC/MS. Progesterone metabolism was similar in both stromal and epithelial cells. To determine if 5α- or 5β-pregnanedione were able to modify PGF 2α synthesis, cells were cultured with P4, 5α- or 5β-pregnanedione (100 ng ml −1) for 48 h and then each group of cells was incubated for a further 4–6 h with or without OT (200 ng ml −1). Results showed that only P4 caused significant ( P < 0.001) increase in basal, but not OT-stimulated, PGF 2α synthesis. OT binding assays showed no significant effect of progesterone or its metabolites on OTR concentration. In conclusion, bovine endometrial cells are able to metabolize pregnenolone and progesterone but neither 5α- nor 5β-pregnanedione altered prostaglandin synthesis or OTR number in endometrial epithelial cells. These data suggest that 5-pregnanediones do not play a role in the regulation OT-stimulated PGF 2α secretion during the bovine estrous cycle.

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Pregnancy, Bovine Somatotropin, and Dietary n-3 Fatty Acids in Lactating Dairy Cows: II. Endometrial Gene Expression Related to Maintenance of Pregnancy

The objectives were to examine the effects of bovine somatotropin (bST), pregnancy, and dietary fatty acids on expression of key endometrial genes and proteins regulating prostaglandin synthesis in lactating dairy cows. Two diets were fed, at about 17 d in milk (DIM), in which oil of whole cottonseed (control diet) was compared with calcium salts of fish oil-enriched lipid (FO). Ovulation was synchronized in cows with a presynchronization plus Ovsynch protocol and cows were inseminated artificially or not inseminated on d 0 (d 0 = time of synchronized ovulation; 77±12 DIM). On d 0 and 11, cows received bST (500mg) or no bST, and were slaughtered on d 17 to recover uterine secretions and endometrial tissue. Number of cows in the control diet: 5 bST-treated cyclic (bST-C), 5 non-bST-treated cyclic (no bST-C), 4 bST-treated pregnant (bST-P), and 5 non-bST-treated pregnant (no bST-P) cows and in the FO diet: 4 bST-treated FO-cyclic (bST-FO-C) and 5 non-bST-treated cyclic (no bST-FO-C) cows. The FO diet increased progesterone receptor (PR) mRNA, and treatment with bST increased PR mRNA concentration in endometrium of no bST-C, but not in no bST-FO-C or no bST-P cows. Concentrations of estrogen receptor-α (ERα) mRNA and protein, and oxytocin receptor (OTR) mRNA were decreased in no bST-P cows compared with no bST-C cows. Treatment with bST tended to increase OTR and ERα mRNA concentrations in cyclic cows fed control or FO diets. Immunohistochemistry demonstrated effects of bST, FO, and pregnancy on distributions of ERα and PR proteins in endometrium. Pregnancy and FO feeding decreased ERα abundance in luminal epithelium. Prostaglandin H synthase-2 (PGHS-2) protein was elevated in pregnant cows and localized to the luminal epithelium. Both FO and bST treatments reduced staining intensity of PGHS-2 protein. Concentrations of prostaglandin E synthase mRNA were elevated in either cyclic or pregnant cows in response to bST, whereas bST decreased prostaglandin F synthase mRNA in pregnant cows. Uterine lumen fluids had more PGF2α and prostaglandin E2 in pregnant than cyclic cows. Uterine lumen fluids of bST-P cows contained more prostaglandin E2 than those from no bST-P cows. In summary, both pregnancy and bST altered endometrial gene expression, and cyclic cows responded differently to bST than pregnant cows. Feeding FO modulated PR, ERα, and PGHS-2 expression and distribution among endometrial cell types in a manner that may favor establishment and maintenance of pregnancy.

Endometrial Oxytocin Receptor Concentration and Activity in Prepubertal Ewe Lambs

We have measured endometrial oxytocin receptor concentrations during prepuberty in ewe lambs, and have investigated the effect of progesterone on the activity of these receptors. In the first study, oxytocin receptor concentrations were undetectable in 2-week prenatal lambs but had increased immediately following birth and were then maintained throughout prepubertal life. Despite the presence of oxytocin receptors animals showed no prostaglandin F(2alpha) (PGF(2alpha)) release in response to exogenous oxytocin challenge at either 3 or 5 months of age. In a second study in 4-month-old ewe lambs treatment with exogenous progesterone resulted in the appearance of PGF(2alpha) release in response to oxytocin after 10 days of treatment. Thus, during the prepubertal life, ewe lambs possess the prerequisites of a luteolytic mechanism in that they have a dormant population of oxytocin receptors in which progesterone can induce oxytocin-stimulated PGF(2alpha) release.

Oxytocin (OT) action in uterine tissues of cyclic and early pregnant gilts: OT receptors concentration, prostaglandin F 2α secretion, and phosphoinositide hydrolysis

Oxytocin (OT) is involved in the regulation of luteolysis in pigs. However, it is still not clear if OT is responsible for initiation of luteal regression in this species. The objectives of the study were: (1) to compare OT receptors (OTr) concentrations in endometrium and myometrium of cyclic and early pregnant pigs, (2) to examine the effect of OT on plasma PGF 2α secretion during the progressive luteal regression, (3) to ascertain the effect of OT on inositol phosphates (IPs) accumulation in endometrial and myometrial cells of cyclic and early pregnant pigs. Concentrations of OTr on the endometrium and myometrium of cyclic ( n = 33) (days 2–4; 11–13; 14–16; 18–20; day 21) and early pregnant ( n = 4) (days 14–16) gilts were determined and they ranged from 7 ± 3 (days 11–13) to 377 ± 113 fmol/mg protein (day 21) in the endometrium and from 33 ± 11 (days 2–4) to 167 ± 28 fmol/mg protein (days 18–20) in the myometrium. In both tissues, concentrations of OTr were low during the luteal phase and increased ( P < 0.01) during the follicular phase. In contrast to myometrial OTr, endometrial OTr during pregnancy were undetectable. In next experiment, mature gilts ( n = 12) were injected with OT (20 IU; i.v.) for three consecutive days starting on days 14 and 15 of the oestrous cycle and plasma PGF 2α metabolite—13,14-dihydro-16-keto PGF 2α (PGFM) concentration was determined. On days 15–16 and 16–17, OT increased plasma PGFM level. This effect was not observed on days 14–15 of the estrous cycle. A negative correlation was noticed between plasma concentrations of PGFM and progesterone ( r = −0.3; P < 0.05). In last experiment, OT (100 nM) augmented ( P < 0.01) an accumulation of inositol phosphates (IPs) in isolated myometrial cells on days 14–16 ( n = 4) and 18–20 ( n = 3) of the estrous cycle and on days 14–16 ( n = 4) of pregnancy. Oxytocin-stimulated accumulation of IPs was not observed in endometrial cells. In summary: (1) concentrations of OTr on both the endometrium and myometrium were the highest during perioestrus-period in pigs, (2) myometrium of early pregnant sows possessed functional OTr, (3) oxytocin increased plasma PGFM concentration after initiation of luteolysis; and (4) OT-stimulated accumulation of IPs in myometrial, but not in endometrial cells. In conclusion, OT appears to not be involved in the initiation of luteal regression in sows and functional OTr are still present in the myometrium during early pregnancy (days 14–16).

The concentrations of catecholamines and oxytocin receptors in the oviduct and its contractile activity in cows during the estrous cycle

In vitro experiments on oviducts of cyclic cows were undertaken to study: (1) the content of dopamine (DA), noradrenaline (NA) and adrenaline (A) in infundibulum, ampulla and isthmus, (2) the concentration of oxytocin receptors (OTR) in oviductal tissues and (3) the motility of ampulla and isthmus. Changes of DA content were observed in the infundibulum and the ampulla with maximal values occurring on Days 6–10 of the estrous cycle. The mean NA content was greatest in infundibulum<ampulla<isthmus. NA concentrations were the highest in the isthmus on Days 1–5 and 16–21, whereas in infundibulum NA levels were low during the whole estrous cycle. Mean A content was the highest ( P<0.001) in the isthmus and in the studied regions of the oviduct A content decreased from Days 1–5 to Days 16–21 ( P<0.01). Oxytocin receptors densities were measured in oviducts collected from cows on Days 16–21 (277.1±151.4 fmol/mg protein; K d 20.5±10.9 nM). Oxytocin (10 −7 M) increased the area under the contractile curve (AUC) of the ampulla and the isthmus on Days 16–21 and of the isthmus on Days 1–5 ( P<0.01). Acetylcholine (Ach) (10 −7 M) stimulated the ampulla and the isthmus contractions on Days 1–5 ( P<0.05) and ampulla contractions on Days 6–10 and 16–21 ( P<0.01). NA (10 −5 M) relaxed the ampulla and the isthmus during most of the studied days but was most effective on Days 1–5 and 16–21 ( P<0.01). In conclusion: (a) catecholamine content in the bovine oviduct varies by region and phase of the estrous cycle, (b) the presence of OTR and the stimulatory effect of oxytocin on oviduct motility are evident in the follicular-phase cows, (c) Ach and NA modify contractile activity in the oviduct of cows during follicular and early-luteal phases and (d) the studied oviductal parameters did not differ by ipsilateral and contralateral relationships to the active ovary in cow.

Immunohistochemical reactivity of myometrial oxytocin receptor in extracorporeally perfused nonpregnant human uteri.

In the pregnant uterus oxytocin and the oxytocin receptor play a major part for uterine contractility and the induction of labor. Clinical evidence implicates that with regard to contractility associated disorders like for example dysmenorrhea also in the nonpregnant and very early pregnant myometrium oxytocin and the oxytocin receptor seem to be more important than believed at the moment. However, little is known about the mutual dependence of the oxytocin receptor, oxytocin and 17-beta-estradiol in the nonpregnant myometrium and about the distribution of the oxytocin receptor in the nonpregnant uterus. Therefore, in the present study we investigated in the nonpregnant myometrium if oxytocin receptor expression can be affected by 17-beta-estradiol and oxytocin stimulation. We used a previously established experimental perfusion system for the human uterus. We perfused 10 uteri for 27 h under physiological conditions without 17-beta-estradiol (group A, n=5) or with high 17-beta-estradiol stimulation (group B, n=5) followed by oxytocin stimulation in both groups in the last 3 h of the experiment. The expression of the myometrial oxytocin receptor in both groups was compared immunohistochemically. In comparison to the negative controls the immunohistochemical reactivity demonstrated increasing oxytocin receptor concentrations with maximum levels under 17-beta-estradiol and oxytocin stimulation in the uterine fundus (40% of positive stained cells, p<0.01). However, oxytocin receptor levels did not reach concentrations comparable to specimen of third trimester of pregnancy, which were used as positive controls. Taken together, our data demonstrate that the dynamics of oxytocin receptor expression can be affected by stimulation with 17-beta-estradiol and oxytocin not only in the pregnant uterus, but also in the nonpregnant uterus. Therefore, dyscontractile phenomena of the nonpregnant myometrium also may be mediated via 17-beta-estradiol, oxytocin and the oxytocin receptor.

Oxytocin induces PGE 2 release from bovine cervical mucosa in vivo

Oxytocin receptor (OTR) concentrations in bovine cervical mucosa rise steeply a few days before estrus to high concentrations and fall rapidly after estrus. To study the physiological role of these OTR, the effect of OT on the release of PGE 2 from the cervical mucosa of periestrous cows in vivo was determined by inserting bags made of dialysis tubing containing isooncotic saline solution in the endocervix for two 2-h periods, a fresh bag for each period. During the first period no treatment was given, during the second period OT (100 IU) or saline was injected i.m. PGE 2 content in the second bag was significantly greater in OT-treated cows than in saline-treated cows. In a second experiment cervical resistance to stretch, achieved by distention of a balloon inside the cervical canal, was measured in periestrous cows before and 10 h after i.m. injection of OT, or endocervical application of 2.5 mg PGE 1 in a jelly, or the inactive jelly. A significant reduction in the resistance was achieved with both OT and PGE 1; in the doses given the effect of PGE 1 was longer lasting than that of OT.

The influence of estradiol and progesterone on the concentrations of uterine oxytocin receptors and plasma PGFM in response to oxytocin in ovariectomized gilts.

Peripubertal gilts (n = 25) were treated with corn oil (CO) or ovarian steroids, one month following an ovariectomy. The first day of treatment was assigned as the first day of the experiment. The gilts received: Group (Gr) I (n = 4)--CO (2 mL x day(-1) from 1st to 12th day), Gr II (n = 4) and Gr III (n = 4)--progesterone (P4; 10 to 100 mg x day(-1) from 1st to 12th day), Gr IV (n = 5)--estradiol benzoate (EB; 400 microg x day(-1) from 1st to 3rd day), Gr V (n = 4) and Gr VI (n = 4)--EB + P4 (EB 400 microg x day(-1) from 1st to 3rd day, 20 microg x day(-1) at 6th and 9th day, 50 microg at 12th day plus P4 10 to 100 mg from 4th to 15th day). All gilts were injected with oxytocin (OT; 20 IU; i.v.) on the following days of the experiment: 13th (Gr I and Gr II), 15th (Gr III and Gr IV), 16th (Gr V) and 18th (Gr VI). Concentrations of the PGF2alpha metabolite--PGFM were determined in blood samples, collected from 30 min before to 120 min after OT injection. Baseline PGFM concentrations (30 min before OT) differed among treatment groups and were the highest in Gr V and Gr VI (P < 0.01 vs. other groups). The magnitude of the PGFM response to OT increased only in four of the five gilts of Gr IV and in three of the four gilts of Gr VI, and it was higher (P = 0.009) in Gr VI than in Gr IV. In the remaining groups, PGFM concentrations did not increase above the baseline in response to OT. The day after OT injection, oxytocin receptors (OTR) were found in the uterine tissues of all animals studied. The lowest OTR concentrations were in Gr I--75.5 +/- 11.2 fmol x mg protein(-1) and the highest in Gr IV--712.9 +/- 86.7 fmol x mg protein(-1); (P < 0.05 vs. other groups). The values of K of OTR differed among groups (P < 0.001) and ranged from 1.62 +/- 0.44 nM in Gr I to 12. 08 +/- 1.9 nM in Gr VI. A positive correlation (r = 0.54; P < 0.01) between plasma E2 and uterine OTR concentrations was observed. In conclusion, E2 and P4 are involved in both PGF2 synthesis/secretion and OTR formation, however, full PGF response to OT does not develop before puberty. Estrogens are evident stimulators of uterine OTR synthesis ingilts.

Bovine Retained Placenta: Hormonal Concentrations in Fetal and Maternal Placenta

The aim of this study was to evaluate the relationship between the occurrence of retention of the fetal membranes (RFM) and the hormonal concentrations of progesterone, estradiol-17β, prostaglandin E 2 (PGE 2), prostaglandin F 2α (PGF 2α), oxytocin (OT), oxytocin receptor (OT-R), endothelin-1 and angiotensin II (Ang II) in the placental tissues of cattle. Parturition was induced in nine Holstein cows by a single injection of PGF 2α on Day 274 of gestation. Six out of nine cows in the induced group did not release the fetal membranes within 12 h after parturition and served as the RFM group, and the remaining three cows in that group, which released their fetal membranes within 12 h, served as the non-RFM group. Five other cows calved spontaneously and served as controls. The placental tissues were collected immediately (0 h) and at 6 h after parturition. The hormonal concentrations were measured by enzyme immunoassay in maternal and fetal placental tissues from RFM, non-RFM and control cows. There were no differences in P4 and E2 concentrations among the RFM, non-RFM and control groups. The mean PGF 2α concentration of the RFM group was lower than those of the non-RFM and control groups in the maternal part of the placenta. In maternal tissues, the OT and OT-R concentrations in the RFM group were lower than those at 0 and 6 h after parturition in the non-RFM group. Additionally, the Ang II concentration of the RFM group in both the maternal and fetal parts of placental tissues tended to be higher than those of the other groups. In conclusion, the present results suggest that ET-1 and Ang II may play differential tissue-specific roles in the placental unit that may amplify the local endocrinological cascade involving OT, OT-R and PGF 2α interactions which are necessary for normal placental separation in the cow.

Oxytocin Receptors, Gap Junctions and the Onset of Human Labor

Oxytocin-Rezeptoren (OTR) und Gap Junctions (GJ) stellen wichtige Strukturen für die Entwicklung und Ausbreitung regelmäßiger, uteriner Kontraktionen dar. Im Verlauf der Schwangerschaft nimmt die Konzentration dieser beiden Moleküle in uterinen Geweben zu, wodurch eine beträchtliche Steigerung der Kontraktilität des Myometriums erzielt wird. Ziel dieser Studie war es, die Ausdehnung der GJ-Formationen mit der Konzentration der OTR im Myometrium während des Schwangerschaftsverlaufes zu vergleichen. Ebenso wurden Proben mit und ohne Wehentätigkeit sowie Gewebe nach frustraner Einleitung mit Oxytocin untersucht.

Oxytocin Links Mothering Received, Mothering Bestowed and Adult Stress Responses

We review recent discoveries that implicate oxytocin in the intergenerational transmission of similar levels of maternal behavior and acute stress responses in female rats. First, ICV-infused oxytocin antagonist decreased the display by nursing dams of pup-licking (PL) and arched-back nursing (ABN), but not other components of maternal behavior, and increased maternal self-grooming suggesting that oxytocin may shift the balance of oral grooming by dams away from themselves and toward pups. Second, oxytocin receptor concentrations in areas of the adult brain where oxytocin stimulates maternal behavior or diminishes anxiety and adrenal axis responses to acute stress were positively related to PL-ABN received during infancy. Third, oxytocin and oxytocin antagonist treatments of pups on postnatal days 2-10, respectively increased and decreased PL by the treated rats when adult and themselves nursing dams. This indicates that oxytocin activity in female pups, which may be regulated by PL-ABN received from their mothers, influences their adult levels of PL. These three lines of evidence suggest that oxytocin selectively enhances PL-ABN by rat dams, which then increases oxytocin activity in female pups and, thereby, facilitates their expression of central oxytocin receptors (and perhaps other aspects of central oxytocin systems) and, consequently, their adult PL-ABN frequencies and acute stress responses.

Hormone control of prostaglandin F 2α production and oxytocin receptor concentrations in bovine endometrium in explant culture

The effect of progesterone and estradiol on basal and oxytocin-stimulated prostaglandin F 2α production and on oxytocin receptor concentrations in endometrium from long term ovariectomized cows was investigated using an explant culture system. Uteri were obtained from cows at slaughter and endometrial explants were cultured in triplicate for up to 96 h in either control media, or media containing progesterone or estradiol. Basal prostaglandin F 2α production was unaffected by progesterone treatment but was stimulated by estradiol treatment in a dose dependent manner. Oxytocin receptor concentrations remained unchanged in control culture and were unaffected by treatment with estradiol while treatment with progesterone caused a dose-dependent inhibition. Responsiveness to oxytocin, in terms of increased prostaglandin F 2α production, developed “spontaneously” over the first 24 h of culture and was unaffected by treatment with progesterone or estradiol. In summary the results reveal a dose-dependent inhibition of oxytocin receptor concentration by progesterone and a dose-dependent stimulation of basal PGF 2α release by estradiol. The reason for the “spontaneous” development of responsiveness to oxytocin remains unknown but may result from the removal of tissue from the influence of an, as yet unidentified, inhibitory factor.