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1.
Porcine uterine tissues were collected from Days 10 to 14 of gestation (peri-implantation period) or corresponding days of the estrous cycle. Results indicated a marked increase in beta transforming growth factors (TGFbeta1, TGFbeta2, and TGFbeta3) and TGFbeta receptor (type I and type II) immunostaining in uterine luminal epithelium (ULE) between Days 10 and 14 of gestation, but there was no increase in ULE immunostaining on the corresponding days of the estrous cycle. Uterine glands and stroma were intensely immunopositive in pregnant gilts for TGFbeta isoforms and their receptors, but immunostaining was weak to undetectable in cycling gilts. No differences were detected in myometrium, in which immunostaining was moderate in both cycling and pregnant gilts. Additionally, TGFbeta2 and TGFbeta receptor (type I and type II) immunostaining was detected in uterine monocyte/macrophage-like cells. Western blotting detected the presence of all three TGFbeta isoforms in uterine luminal flushings. The CCL64 cell TGFbeta bioassay detected bioactive TGFbetas++ in uterine luminal flushings on Days 12, 13, an 14 of gestation. These results strongly indicate that uterine expression of TGFbetas and their receptors is pregnancy specific and that bioactive TGFbetas are present at the conceptus-maternal interface in the peri-implantation period in pigs. Thus TGFbetas are likely to be involved in autocrine-paracrine interactions between the maternal uterus and the conceptus.  相似文献   

2.
Ultrastructural changes in the uterine tube (oviduct) of pregnant gilts have been investigated with special reference to the ciliated, secretory, and stromal cells. Tissue from the uterine tube ampulla and infundibulum was taken from 18 gilts at different stages of gestation (days 31, 36, 101, 102, 107, 110, and 112). Cilia were present throughout pregnancy, and deciliation was not apparent at any stage of gestation. The low epithelium of the uterine tube appeared similar to that of the luteal phase of the estrous cycle when corpora lutea were full grown. Prominent features at end of the gestation were numerous fibrous granules and basal bodies, indicating active formation of ciliary precursor organelles. Fibrogranular aggregates were also present in association with the basal bodies. In addition, numerous polyribosomes, mitochondria, and microtubules were encountered in the cytoplasm of ciliated cells at end of the gestation. The appearance of electron-opaque, fibrous granules during late pregnancy probably could be correlated with increasing endogenous levels of plasma estrogen. Intimate morphologic association between fibrous granules and basal bodies indicate that fibrous granules might provide precursor material for the development of cilia or rootlets. Characteristics ultrastructural changes observed in secretory cells during the estrous cycle were not discernible in secretory cells during pregnancy. The secretory cells appeared similar to those of the luteal phase of the estrous cycle. The apocrine secretory cells contained prominent, apical, cytoplasmic projections; pinching-off process of these protrusions was frequently observed during early and term gestation. Extruded nuclei along with other cytoplasmic organelles were also present, lying free in the tubal lumen. The endoplasmic reticulum was predominantly tubular in form. Synthesis, storage, and release of secretory granules were not apparent at early or late pregnancy. It is suggested that progesterone might have an inhibitory effect on the synthesis, storage, and release of secretory granules. Ultrastructural changes in stromal cells were not apparent at any stage of gestation. The stromal cells appeared similar to that of the luteal phase of the estrous cycle.  相似文献   

3.
The amount and the labelling of RNA were studied in chick oviduct after secondary stimulation of pre-treated chicks with oestrogen. The weight of the oviduct increases over 2 fold in 20 h of oestrogen action using a dose of 1 mg. During the hormonal treatment the amount of cytoplasmic and nuclear RNA increases about 3 and 1.5 fold, respectively. The amount of poly(A) containing RNA increases somewhat less than that of RNA lacking poly(A). The proportion of poly(A) containing species of the total cytoplasmic and nuclear RNA decreases from 5.8% to 4.4% and from 7.8% to 6.3%, respectively. Hydroxyurea largely prevents the effect of oestrogen in increasing the amount of RNA. Incorporation of [3H]uridine in RNA in vitro is stimulated about 2.5 fold in cytoplasmic RNA lacking poly(A) and only 1.2 fold in RNA containing poly(A) in 20 h of oestrogen action. In nuclear RNA the labelling of the two species is stimulated about 1.7 fold. Hydroxyurea fails to interfere with the oestrogen-induced stimulation in the labelling of RNA. Cytoplasmic and nuclear RNA containing poly(A) is distributed in a peak of about 20 S in agarose-acrylamide gels.  相似文献   

4.
Little is known about the mechanism responsible for retarded placental and fetal growth induced by maternal dietary protein malnutrition. On the basis of the recent finding that nitric oxide (NO) and polyamines (products of L-arginine) play an important role in embryonic and placental development, the present study was designed to determine whether protein deficiency decreases placental and endometrial activities of NO synthase (NOS) and ornithine decarboxylase (ODC) (the first and key regulatory enzyme in polyamine synthesis). Primiparous gilts selected genetically for low or high plasma total cholesterol concentrations (low line and high line, respectively) were mated and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5% crude protein. At d 40 or 60 of gestation, they were hysterectomized, and placenta and endometrium were obtained for incubations, NOS and ODC assays, and measurements of free amino acids and polyamines. Maternal dietary protein restriction decreased arginine and ornithine concentrations, constitutive and inducible NOS activities and NO production, as well as ODC activity and polyamine concentrations in placenta and endometrium of both lines of gilts. Placental NO synthase activity and NO generation were lower in high line gilts than in low line gilts. ODC activities and polyamine concentrations in placenta and endometrium were decreased at d 60 compared with d 40 of gestation. These changes in placental and endometrial synthesis of NO and polyamines during early gestation may be a mechanism responsible for reduced placental and fetal growth in protein-deficient gilts and for altered conceptus development in high line gilts.  相似文献   

5.
Previous reports suggest that tissue factor (TF) may play an essential role in embryonic vascular development and tumor angiogenesis. To further examine this relationship, the morphology of fully developed TF-deficient embryos and the growth of TF-deficient teratomas and teratocarcinomas were analyzed. In a 129/Sv genetic background, TF null embryos do not survive beyond mid-gestation. In contrast, 14% of 129/Sv x C57BL/6 TF-deficient embryos escape this early mortality and survive to birth. On gross and microscopic inspection, these late gestation, TF-deficient embryos appear normal. The growth and vascularity of TF(+/+), TF(+/-), and TF(-/-) teratomas and teratocarcinomas are indistinguishable. Thus, tumor-derived TF is not required for tumor growth and angiogenesis and the combined data do not support an essential role for TF in embryonic vascular development.  相似文献   

6.
The peptide hormone calcitonin plays a key role in calcium homeostasis in many tissues, such as bone and kidney. Our previous studies revealed that the expression of calcitonin is dramatically induced in the glandular epithelium of rat uterus between days 3-5 of pregnancy before the onset of blastocyst implantation on day 5. Calcitonin expression is switched off once implantation has progressed to day 6. The coincidence in timing suggested that calcitonin may function as a regulatory signal in the uterus during the early events leading to implantation. Here we report that the implantation stage-specific expression of calcitonin can be specifically attenuated by administering antisense oligodeoxynucleotides (ODNs) directed against exon IV of calcitonin messenger RNA into the uterine horns on day 2 of gestation. The loss of calcitonin messenger RNA and protein expression upon antisense ODN treatment is accompanied by a severe impairment in implantation of embryos. Based on the observations that 1) treatment with two different antisense ODNs possessing different base compositions produced similar phenotypes; and 2) treatment with the complementary sense ODNs did not affect either calcitonin expression or implantation, we conclude that the effects of antisense ODNs on calcitonin expression and implantation are specific and functionally linked. Our study strengthens the hypothesis that a transient expression of calcitonin in the preimplantation phase uterus is critical for blastocyst implantation.  相似文献   

7.
This experiment consisted of the following treatment-breed groups: 1) White crossbred gilts, 2) White crossbred gilts treated with progesterone (200 mg/d in corn oil given on d 2 and 3 after estrus), and 3) Chinese Meishan gilts. Pregnant and nonpregnant gilts (n=3 to 6) from each treatment-breed combination were assigned to be slaughtered on d 10, 11, 12, 13, and 15. At slaughter each uterine horn was flushed with 20 mL of minimal essential medium. Uterine flushings were assayed for total protein, acid phosphatase, uteroferrin, retinol-binding protein, and oxytocin. Uterine flush total protein was increased by progesterone treatment, was unaffected by pregnancy status, and was less in Meishans. Similar patterns were found for retinol binding protein and uteroferrin, except that uteroferrin was greater in pregnant than in nonpregnant gilts. Oxytocin was greater in pregnant than in nonpregnant gilts, was not influenced by progesterone treatment, and was similar in Meishan and in White crossbred gilts. These results indicate that the conceptus does not influence secretion of either total protein or retinol binding protein during pregnancy and that the onset of secretion of these uterine proteins may be controlled by progesterone. The presence of the conceptus is associated with increased uteroferrin and oxytocin production. The decreased secretion of uterine proteins in Meishan gilts may partially explain the slower embryonic development that has been reported for this breed.  相似文献   

8.
Previously, postcoital antifertility effects of a number of aminoalcohols, including 2-(isopropylamino)-ethanol, have been demonstrated in rodents. In this experiment, we compared the antifertility activity of 2-(isopropylamino)-ethanol to the following analogs: hydroxyethylpiperidine, hydroxyethylpiridine, hydroxyethylpirrolidine, and hydroxyethylpirrolidone. Female rats were gavaged on Days 0 through 5 of gestation with 0.7 mmol/kg/d of these substances. Only 2-(isopropylamino)-ethanol and hydroxyethylpirrolidine showed a strong antifertility activity: females treated with 2-(isopropylamino)-ethanol had no signs of implantation, whereas those treated with hydroxyethylpirrolidine had 100% early resorptions. Treatments with these two substances during the periimplantation period (Days 4 and 5) produced 100% early resorptions. Histologic examination of the implantation sites showed signs of embryonic degeneration starting from Day 6.5 of gestation. The flushing of the uteri of females treated with 2-(isopropylamino)-ethanol on Days 0 through 3 post coitum showed 78% of the embryos at the stage of 1 to 3 blastomeres, whereas the embryos of females treated during the same period with hydroxyethylpirrolidine were normal blastocysts. Therefore, 2-(isopropylamino)-ethanol and hydroxyethylpirrolidine are able to kill embryos during the early implantation stages, whereas 2-(isopropylamino)-ethanol is also able to stop the development of preimplantation embryos.  相似文献   

9.
Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of both acute and chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited TNF-alpha production from macrophages by destabilizing its messenger RNA. This effect appeared to result from direct TTP binding to the AU-rich element of the TNF-alpha messenger RNA. TTP is a cytosolic protein in these cells, and its biosynthesis was induced by the same agents that stimulate TNF-alpha production, including TNF-alpha itself. These findings identify TTP as a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies.  相似文献   

10.
It has been proposed that short-term activation of the hypothalamo-pituitary adrenal axis, with a consequent increase in the secretion of cortisol, amy disrupt the endocrine events prior to ovulation and thereby impair reproduction in females. We investigated this concept in gilts in which oestrus was detected by introduction to boars, where intense physical contact is possible, or by applying pressure to the back of gilts (back-pressure test) during fence-line exposure to boars, where intense physical contact is prohibited. We expected that there would be a greater release of cortisol and that reproduction would be inhibited in gilts introduced to boars compared to gilts in which the back-pressure test was used. As expected, introduction of gilts to boars resulted in a significant transient increase in plasma concentrations of cortisol while there was no significant effect of using the back-pressure test on plasma cortisol. Nevertheless, introduction of gilts to boars did not impair reproduction and there was no effect of method of detecting oestrus on duration of oestrus, sexual receptivity, fertility or fecundity. The length of the oestrous cycle was decreased and ovulation rate increased in gilts that were introduced to boars compared to gilts that underwent the back-pressure test, indicating that introduction of gilts to boars may have stimulated these aspects of reproduction. These stimulatory effects may have been due to an increased exposure of gilts to sexual behaviour and stimuli from boars when introduced to boars and/or to stimulatory effects of the hypothalamo-pituitary adrenal axis on some aspects of reproduction.  相似文献   

11.
Rats were exposed to gamma rays or helium ions on one of days 4-9 of gestation. Embryonic survival was recorded as a function of intrauterine position at autopsy on day 20 of gestation. Embryos located at the ovarian and cervical ends of the uterus experienced higher rates of mortality than did their littermates located at the middle of the uterine horn. This effect was observed in litters exposed to both radiation modalities on all days studied. The influence of intrauterine position on embryonic survival was directly proportional to radiation dose and to the number of fetuses occupying the uterus horn. Under the least advantageous conditions (i.e., a crowded uterine horn exposed to a moderately high radiation dose), the cervical embryo's probability of survival was less than half that of the litter as a whole. A disproportionately high rate of embryonic mortality at the cervical position was also observed in litters irradiated under hypoxic conditions, suggesting that the non-random distribution of radiation effect was not the result of variations in oxygen concentration within the uterus. In contrast, there was no indication that intrauterine position influenced the distribution of gross morphologic abnormalities in irradiated litters.  相似文献   

12.
To evaluate the biocompatibility of dialysis membranes, blood samples were collected from 10 hemodialysis patients immediately before dialysis and peripheral blood mononuclear cells were isolated. The 3.0 x 10(5) cells/ml were then passed 30 times through modules made of a polyethylene glycol-grafted cellulose membrane, a polyacrylonitrile membrane, and a polysulfone membrane. Expression of messenger RNA for tumor necrosi factor-alpha (TNF-alpha) was determined. Cells were also cultured for 2 h with and without lipopolysaccharide and TNF-alpha levels in the supernatant were measured. TNF-alpha messenger RNA expression was significantly higher immediately after passage through the polyacrylonitrile membrane compared with the other membranes. Cells cultured without lipopolysaccharide, produced significantly less TNF-alpha after passage through the polysulfone membrane, while lipopolysaccharide significantly increased TNF-alpha production by cells passed through the polyacrylonitrile membrane. These results suggest that biocompatibility differs even among dialysis membranes believed to cause no complement activation.  相似文献   

13.
Co-cultures of embryos with somatic cells, usually in the form of monolayers, or conditioned medium from these somatic cells, results in development past the early stage blocks and the formation of hatched blastocysts. Optimum rates of development are not achieved, however, and the task is to investigate components of the oviduct that are obligatory or facilitative for embryo development. Glycine and alanine are amino acids present in much higher concentrations in oviduct fluid than in serum or culture media. Glycoproteins specifically produced by the oviduct around oestrus bind to embryos and aid development but are absent from most culture media. These glycoproteins are induced by oestrogen in vivo but not in vitro. It is our contention that co-cultures of mammalian embryos should include appropriate concentrations of amino acids and a source of embryotrophic glycoproteins as an additive or by including stromal cells in addition to epithelial cells.  相似文献   

14.
Experiments were carried out to study: the effects of season on age at puberty, the influence of reproductive age on ovulation rate, and the time interval from the onset of oestrus to ovulation in Chinese Meishan gilts. Gilts approaching puberty either in the spring (n = 88) or in the autumn (n = 40) were housed indoors under natural daylight conditions and observed daily for oestrous behaviour. Gilts approaching puberty in the spring were younger (P < 0.001) and more likely to reach puberty by 100 days of age (P < 0.01) than were those approaching puberty in the autumn. Ovulation rate was estimated in gilts at second (n = 22), third (n = 24), fourth (n = 18), fifth to ninth (n = 9) and tenth to twenty-first (n = 17) oestrous cycle and in primiparous Meishan sows (n = 12) by counting the number of corpora lutea or corpora albicantia at laparoscopy, laparotomy or at ovarian recovery following slaughter. Ovulation rate increased (P < 0.001) with reproductive age and approached that of primiparous sows only when gilts had experienced > or = 10 oestrous cycles (19.2 versus 21.0). The time interval between the onset of oestrus and ovulation was studied in six naturally cyclic Meishan gilts and nine Meishan gilts administered hCG at the onset of oestrus. All glits were observed six times a day for the commencement of oestrous behaviour and were subsequently examined by laparoscopy at 32 h following onset of oestrous and every 8 h till ovulation, which was a maximum of 56 h.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
Serotonin has been shown to affect the development of the mammalian nervous system. The serotonin transporter is a major factor in regulating extracellular serotonin levels. Using in situ hybridization histochemistry the rat serotonin transporter messenger RNA was localized during embryogenesis, the first four weeks postnatally and adulthood. Three general classes of serotonin transporter messenger RNA expression patterns were observed: (i) early detection with continued expression through adult age, (ii) transient expression colocalized with vesicular monoamine transporter 2 messenger RNA but with no detectable tryptophan hydroxylase immunoreactivity, and (iii) transient expression in the apparent absence of both vesicular monoamine transporter 2 messenger RNA and tryptophan hydroxylase immunoreactivity. For example, hybridization for serotonin transporter messenger RNA was strong in serotonin cell body-containing areas beginning early in gestation, and remained intense through adulthood. Immunoreactivity for tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, was completely overlapping with the presence of serotonin transporter messenger RNA in raphe nuclei postnatally. Sensory relay systems including the ventrobasal nucleus (somatosensory), lateral and medial geniculate nuclei (visual and auditory, respectively) as well as trigeminal, cochlear and solitary nuclei were representative of the second class of observations. In general, the limbic system expressed serotonin transporter messenger RNA in the third pattern with various limbic structures differing in the timing of expression. Septum, olfactory areas and the developing hippocampus contained serotonin transporter messenger RNA early in the developing brain. Other regions such as cingulate and frontopolar cortex exhibited hybridization peri- and postnatally, respectively. Several hypothalamic nuclei and pituitary transiently expressed serotonin transporter messenger RNA either postnatally or perinatally, respectively. If the observed patterns correlate with functional protein expression, distinct classes of serotonin transporter messenger RNA expression may reflect different functional roles for the serotonin transporter and serotonin, itself. Since the serotonin transporter is a target for a number of addictive substances including cocaine and amphetamine derivatives as well as antidepressants, transient expression of the serotonin transporter might suggest a window of vulnerability of associated cells to fetal drug exposure. Re-uptake, storage and re-release from non-serotonergic neurons might serve as a feedback mechanism from target neurons to serotonergic neurons. Alternatively, the transient expression of serotonin transporter messenger RNA may reflect critical periods important for tight regulation of extracellular serotonin in several brain regions, and may indicate previously unappreciated roles for serotonin as a developmental cue.  相似文献   

16.
Studies were conducted to determine whether the corticosteroids cortisol and aldosterone, and corticosteroid-binding globulin (CBG) were present in the porcine early-embryonic environment. Cortisol was measured in uterine flushings from white crossbred gilts at Days 7, 10, 13, and 16 of the estrous cycle and pregnancy. Total content of cortisol increased (p < 0.01) between Days 13 and 16, and immunoreactive CBG (ir-CBG) increased (p < 0.01) between Days 10 and 13, in both cyclic and pregnant gilts. In a separate study with Chinese Meishan gilts, total cortisol and aldosterone content of uterine flushings increased (p < 0.02) between Days 10 and 15 of the estrous cycle and pregnancy. In another study with white crossbred gilts, CBG-like binding activity in uterine flushings was low at Day 10, then increased over 100-fold at Day 15 (p < 0.01). However, levels of CBG-like binding activity on Day 15 were 100-fold lower than those of ir-CBG measured in the previous study and could bind less than 4% of the uterine luminal cortisol. Differences between ir-CBG and CBG binding might be due to the ability of the CBG antibody to recognize either biologically inactive CBG or structurally similar molecules. CBG-like binding activity, which appeared unrelated to glucocorticoid receptors, was also present in the endometrial cytosol of white crossbred gilts. Concentrations (fmol/mg protein) of endometrial CBG-like activity decreased (p = 0.03) between Days 10 and 15 of the estrous cycle and pregnancy, did not differ with reproductive status, and on Day 15 were comparable to concentrations in uterine flushings but threefold lower (p < 0.01) than those in the serum. Equilibrium dissociation constants for CBG-like binding activities were comparable among the three locations. These studies indicate that corticosteroids are present-primarily in the free form-within the porcine uterine lumen and could influence early porcine conceptus development. Endometrial CBG-like binding activity could mediate actions of cortisol or progesterone on uterine function.  相似文献   

17.
This study investigated the effects of feeding the orally active progestagen, altrenogest (Regumate) post-weaning on the subsequent reproductive performance of early weaned sows. Ninety (90) Large White/Landrace first parity sows were randomly assigned to three treatments. Treatment 1 (EW) and treatment 3 (CW) sows were weaned on day 12 and day 24 post-partum, respectively while treatment 2 sows (EW-R) were weaned on day 12 post-partum and received an individual daily dose of 20 mg of Regumate on days 13 to 24 post-partum inclusive. Each sow was mated naturally at least twice at the first post-weaning or post-treatment oestrus and slaughtered on days 25-28 of pregnancy to determine the number of corpora lutea and embryos. Regumate-to-oestrus and weaning-to-oestrus intervals were similar for EW-R and CW sows (6.2 vs. 5.6 days). However, both intervals were significantly shorter (P < 0.01) than the weaning-to-oestrus interval of EW sows (7.3 days). An excellent synchronization of oestrus was achieved with Regumate treatment with 97% of treated sows in oestrus within 7 days of Regumate withdrawal compared with 64% for EW sows (P < 0.01) and 87% for CW sows (P > 0.05). Treatment with Regumate resulted in a significant increase in ovulation rate (16.9 vs. 15.4 and 14.9 for treatments EW-R, EW and CW, respectively; P < 0.05) and a non-significant increase in early embryonic survival (77% vs. 68% vs. 68% for treatments EW-R, EW and CW, respectively; P > 0.05). These results indicate that Regumate feeding is a potential management tool to alleviate the diminished reproductive performance associated with early weaning regimes since it leads to successful control of oestrus, higher ovulation and embryo survival rates and thus a greater potential litter size.  相似文献   

18.
Vasoactive intestinal peptide (VIP) is an important growth regulator of the embryonic day (E)9-E11 mouse. In comparably aged rat embryos, VIP messenger RNA (mRNA) is not detectable; however, peak concentrations of VIP in maternal rat serum indicate a nonembryonic source. In the current study, mouse maternal and embryonic tissues were examined from E6-E12. Although RT-PCR revealed VIP mRNA in E6-E7 conceptuses, by E8 (when extraembryonic tissues could be separated from the embryo), VIP mRNA was detected only in the decidua/trophoblast. Decidual/trophoblastic VIP mRNA decreased until E10, after which it was not detectable. VIP mRNA was not apparent in the embryo until E11-E12. At E9, VIP immunoreactivity was localized to abundant, diffuse cells in the decidua basalis, which were also immunoreactive for T cell markers. VIP binding sites were dense in the decidua/trophoblast at E6, but gradually decreased until E10, after which they were not apparent. VIP binding sites were detected in embryonic neuroepithelium by E9. The transient presence of VIP binding sites and mRNA in the decidua/trophoblast correlate with the critical period of VIP growth regulation, when VIP mRNA is absent in the embryo. These findings suggest that maternal lymphocytes are the source of VIP's regulating early postimplantation embryonic growth.  相似文献   

19.
20.
We mapped the distribution of CB1 and CB2 receptor messenger RNAs in the developing rat to gain insight into how cannabinoids may affect embryogenesis. In situ hybridization histochemistry studies were done using riboprobes specific for CB1 or CB2 receptor messenger RNAs. We found that CB1 and CB2 receptor messenger RNAs are expressed in the placental cone and in the smooth muscle of the maternal uterus at the earliest gestational periods studied [from eight days of gestation (E8) through E12]. In the embryo, as early as E11, CB1 receptor messenger RNA is expressed in some cells of the neural tube and, at later embryological stages (from E15 to E21), in several distinct structures within the central nervous system. In addition, high levels of CB1 receptor messenger RNA were also found in areas of the peripheral nervous system such as the sympathetic and parasympathetic ganglia, in the retina and in the enteric ganglia of the gastrointestinal tract. In addition to neural structures, high levels of the CB1 receptor messenger RNA were also present in two endocrine organs, the thyroid gland and the adrenal gland. On the other hand, CB2 receptor messenger RNA is expressed exclusively in the liver of the embryo as early as E13. The region-specific expression of CB1 and CB2 receptor messenger RNAs suggests that these receptors have a functional role during embryogenesis.  相似文献   

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