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Biomedical subjects

F W Bazer

Publications and source records attributed to F W Bazer.

At least 217 records · Page 12Linked to original sources

Effects of early pregnancy and acute 17 beta-estradiol administration on porcine uterine secretion, cyclic nucleotides, and catecholamines.

This study investigated acute effects of 17 beta-estradiol (E) on ions, cyclic nucleotides, and catecholamines and their association with temporal changes in uterine secretory products in pregnant, cyclic, and nonpregnant gilts. Uterine flushings (UTF) and endometrium (ENDOM) from one uterine horn of nonpregnant and pregnant gilts (n = 9) were collected on days 10, 12, and 14 (n = 3). Protein, plasma inhibitor (P less than 0.05), Na+, and K+ (P less than 0.01) increased linearly in UTF of pregnant gilts. Ca2+ changed biphasically, with higher concentrations (P less than 0.01) in pregnant gilts on day 12. Endometrial cAMP and cGMP (P less than 0.05) increased between days 12 and 14 of pregnancy. The UTF norepinephrine (NE) concentrations increased (P less than 0.01) in cyclic gilts between days 12 and 14, while endometrial NE increased between days 10 and 12 and then decreased on day 14. The UTF of pregnant gilts had higher (P less than 0.05) concentrations of dopamine (DA), which peaked on day 12 and then decreased (P less than 0.01) by day 14. DA in UTF of nonpregnant gilts decreased between days 10 and 12 and remained low on day 14. A catecholamine metabolite, 3,4-dihydroxyphenylglycol, in ENDOM (P less than 0.05) and UTF (P less than 0.01) decreased linearly between days 10 and 14. The turnover rate of endometrial catecholamines was 2.4-fold higher (P less than 0.05) during early pregnancy compared with that in cyclic gilts. Effects of acute administration of exogenous E (0.5 mg) were also studied. The UTF and ENDOM were from day 11 nonpregnant gilts 0, 30, 60, and 360 min (n = 3) post-E or post-saline-ethanol (C) injection (n = 9). Potassium, plasma inhibitor (P less than 0.01), and cGMP (P less than 0.05) increased rapidly (30 min) after E injection. The K+ level changed biphasically, with increased concentrations again at 360 min. Plasmin inhibitor returned to levels similar to controls by 60 min, whereas cGMP remained elevated until 360 min postinjection when E, Ca2+, K+ (P less than 0.01), and Na+ (P less than 0.03) were increased. ENDOM NE (P less than 0.05) and UTF DA (P less than 0.05) were lower in E-treated gilts. Additionally, the turnover rate was significantly lower (P less than 0.05) for NE and DA in the UTF of E-treated gilts. An increase in Ca2+ in UTF preceded increases in protein secretions (except plasmin inhibitor) and may play a role in E-stimulated endometrial epithelial secretory vesicle exocytosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗

Beta-endorphin in uterine secretions of pseudopregnant and ovariectomized, ovarian steroid-treated gilts.

Levels of beta-endorphin-like immunoreactivity (beta END-LI) in uterine secretions were studied in pseudopregnant and ovariectomized gilts treated with ovarian steroids. Pseudopregnancy was induced in 7 gilts by daily injection of estradiol valerate (5 mg/day) between days 11 and 15 of the estrous cycle. Between days 60 and 90 of pseudopregnancy, uterine secretions were collected by flushing the uterus with 0.9% saline. Uterine flushings were extracted with a Sep-Pak C-18 column and assayed for beta END-LI by a specific RIA. The RIA cross-reacted only with beta-lipotropin (15%). Significant amounts of total immunoreactive beta END-LI were detected in the uterine flushings. The inhibition curve for extracts was parallel to the standard END inhibition curve. Extracted uterine flushings were applied to a Sephadex G-50 column. Three peaks of immunoreactive beta END-LI were detected. One peak eluted at the void volume. The second peak eluted at a Kav of 0.21, which was near the Kav of a lipotropin standard (0.23). The highest peak (Kav = 0.53) eluted similar to standard END (Kav = 0.51). In the second experiment, 12 gilts were ovariectomized on day 4 of the estrous cycle and randomly assigned to 4 groups of 3 gilts each. Each group received 1 of the following daily injections: vehicle (corn oil), 0.1 mg 17 beta-estradiol (E2), 200 mg progesterone (Prog), or a combination of E2 and Prog (E2 + Prog). After treatment for 30 days, beginning on the day of ovariectomy, the uterine flushings were assayed for beta END-LI and total protein. Treatment with Prog increased (P less than 0.05) total beta END-LI 532% (12.4 ng) compared to corn oil treatment (2.3 ng), and levels were significantly higher than with E2 (2.9 ng) or E2 + Prog treatment (5.1 ng). Opiate receptor assay showed that extracts of uterine flushing had a displacement curve parallel to that of standard porcine beta END. Results suggest that significant amounts of immunoreactive beta END-LI are present in uterine secretions of gilts and that the accumulation of beta END-LI is influenced by ovarian steroids.

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Identification of bovine trophoblast protein-1, a secretory protein immunologically related to ovine trophoblast protein-1.

This paper demonstrates that a group of proteins, representing a major secretory component of cattle conceptuses, is immunologically related to ovine trophoblast protein-1 (oTP-1), a principal product of culture Day 13 to 21 sheep conceptuses. Conceptuses from cows (Day 17-18) and ewes (Day 16-17) were cultured for 24 h in the presence of L-[3H]leucine. By using a rabbit antiserum to oTP-1 and Ouchterlony double-immunodiffusion analysis it was shown that material in the bovine conceptus culture medium was serologically related, but not identical, to oTP-1. A solid-phase radiobinding assay indicated that the cross-reacting bovine secretory component had an affinity for anti-oTP-1 antibody similar to that of oTP-1. Anti-oTP-1 antiserum specifically immunoprecipitated a group of 6-8 polypeptides from culture medium of cow conceptuses which, when analysed by two-dimensional gel electrophoresis, fell into two major molecular weight classes (22,000 and 24,000) with isoelectric points between 6.5 and 6.7. These immunoprecipitated polypeptides, defined as bTP-1, constituted the major secretory products of Day 16-25 cow conceptuses. They were larger and more basic than oTP-1 polypeptides (Mr about 18,000; pI 5.4-5.7). Anti-oTP-1 antiserum also recognized the major translation product of Day 17 bovine conceptus mRNA, a polypeptide significantly smaller (Mr approximately 18,000) than the secreted protein. It is suggested that oTP-1 and the homologous bovine protein may play similar roles in the phenomenon of maternal recognition of pregnancy in the two species.

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Secretory function of the ovine uterus: effects of gestation and steroid replacement therapy.

In Exp. 1, changes in uterine fluid content of protein, calcium and prostaglandin F2 alpha (PGF) were examined between d 30 to 144 of gestation. Volume of uterine fluid (mean +/- SE) in the nongravid uterine horn of unilaterally pregnant ewes increased (P less than .05) between d 30 (8 +/- 1 ml) and d 144 (749 +/- 46 ml) of gestation. Protein concentration and total protein in uterine fluid also increased (P less than .05) between d 30 (2.3 +/- .4 mg/ml; 19 +/- 7 mg) and d 144 (23.5 +/- 3.3 mg/ml; 17.4 +/- 2.0 g). Total recoverable calcium (mg) in secretions increased from .1 mg (d 30) to over 1.4 g (d 144) due to day of gestation effects (P less than .05). Total PGF also increased (P less than .01) from 7 ng on d 30 to 15.7 g on d 144. In Exp. II, ovariectomized (OVX) ewes were treated with either corn oil, estrone (E), progesterone (P) or P+E (PE) for 30 d. Treatment with P or PE increased calcium concentration and content (P less than .01) in secretions, but differences in uterine fluid volumes and concentrations of protein and PGF were not significant. Treatment of OVX ewes with P stimulated (P less than .05) in vitro synthesis of secretory proteins by endometrium, whereas treatment with E enhanced release of unlabeled proteins (P less than .05). The major endometrial secretory proteins were identified in allantoic fluids from d 60 to term and were detected along the mesenchymal border of the chorioallantois using immunohistochemistry. Results from this study indicate that P may be a primary hormone regulating accumulation of fluid, protein, calcium and specific endometrial proteins in the uterine lumen during gestation, and that uterine milk proteins gain access to the fetal-placental unit.

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Isolation and characterization of a high molecular weight stable pink form of uteroferrin from uterine secretions and allantoic fluid of pigs.

A pink, high molecular weight form of uteroferrin (Uf) has been isolated from uterine secretions and allantoic fluid of pigs. This protein fraction (denoted FIII) which is relatively stable under physiological conditions of pH, ionic strength, and temperature has a molecular weight of about 80,000, a value approximately twice that of purple Uf (Mr approximately 35,000) isolated from a separate fraction (FIV) by gel filtration. The visible absorption spectrum, EPR signal, and acid phosphatase activity of Uf in FIII are almost identical to those of FIV Uf after the latter has been reduced by 2-mercaptoethanol. However, unlike reduced FIV Uf, the pink, high molecular form does not revert to purple, nor does it show loss of EPR signal and phosphatase activity in the presence of oxygen. In addition, it does not become purple at orthophosphate concentrations which inhibit Uf acid phosphatase activity. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate has shown that FIII consists of approximately equal amounts of Uf polypeptides (Mr = 35,000 and 37,000) and a group of three polypeptides (Mr = 40,000, 46,000, and 50,000) antigenically unrelated to Uf. The latter share a common epitope not found on Uf and are probably differentially processed forms of the same protein. FIII can be dissociated by pH conditions below 5.0, by exposure to antibodies raised against Uf or the associated polypeptides, and by sodium dodecyl sulfate at 100 degrees C. The polypeptides in FIII are not therefore linked by disulfide bonds. Treatment with dimethyl suberimidate, however, results in a cross-linked complex (Mr approximately 82,000) consisting of Uf and the associated polypeptides. It is concluded that this high Mr form of Uf is a heterodimer of fully activated Uf and a second polypeptide of unknown function.

Acid Phosphatase↗

Inhibition of uterine prostaglandin-F2 alpha production by bovine conceptus secretory proteins.

The effect of bovine conceptus secretory proteins (CSP) on uterine prostaglandin (PG)-F2 alpha production was evaluated in dairy cattle following injection of estradiol-17 beta. Intrauterine injections of dialyzed serum proteins (Control, n = 5) or CSP (n = 5) were administered from days 15 through 18 post-estrus. Following intrauterine treatments on day 18, all cows were injected with E2 (3 mg) to stimulate uterine PGF2 alpha production. Plasma concentrations of progesterone (P4) and 15-keto-13,14-dihydro-PGF2 alpha (PGFM) were determined by RIA. The PGFM responses following E2 challenge were decreased (p less than 0.01) for cows receiving CSP versus serum proteins into the uterine lumen. Individual PGFM, P4 and cycle length responses are discussed. Data suggest that proteins secreted by the bovine conceptus suppress uterine PGF2 alpha production during pregnancy recognition in the cow.

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Relationship between estrone sulfate in plasma and litter size at farrowing for sows and gilts.

A positive association (P < 0.01) was detected between estrone sulfate (ES) concentrations in maternal plasma at Day 30 of pregnancy and litter size at parturition in swine. This relationship was best described by a fifth order regression equation (R(2) = 0.5) which indicated that as ES increased from 1 to 7.5 ng/ml on Day 30, litter size increased from 0 (nonpregnant) to 18 piglets farrowed. Day of sampling (P < 0.02), month (P < 0.04) and parity (P < 0.08) were major sources of variation in the model. This indicated that effects of environmental factors such as heat stress, which influence conception rate and embryonic survival, are reflected in changes in maternal ES. Also, larger litter size associated with parous sows is reflected in increased ES in maternal plasma. We conclude that measurement of ES early in gestation may be useful in reproductive management to identify nonpregnant gilts and sows as well as those with small litters.

Journal Article↗

Interrelationships between uterus and conceptus to maintain corpus luteum function in early pregnancy: sheep, cattle, pigs and horses.

Processes associated with "Maternal Recognition of Pregnancy" are reviewed extensively from the ovine, bovine, porcine and equine species. Comparisons among these species indicate that CL maintenance is achieved primarily by a predominant antiluteolytic-anti PGF effect, and there is strong evidence for antiluteolytic-luteoprotective and luteotropic controls that complement this basic system. The nature of the chemical signals (steroids, prostaglandins and proteins) to regulate these processes among the species are described. Common to all of the species reviewed is a change in vascular dynamics to and from the uterus and ovary during early pregnancy. The dialogue between endometrial epithelium and trophectoderm of the developing conceptus is described. The consequence of these various physiological and biochemical responses of early pregnancy is maintenance of the CL to provide a sustained embryotrophic environment. Either in the absence of or death of a conceptus, an efficient and acute system is operational to terminate this progestational environment via regression of the CL through uterine production of PGF.

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Prostaglandin F2 alpha as the luteolysin in swine: VI. Hormonal regulation of the movement of exogenous PGF2 alpha from the uterine lumen into the vasculature.

To test the endocrine-exocrine theory of maternal recognition of pregnancy in the pig 16 gilts were assigned randomly to a 2 X 2 factorial involving pretreatment with sesame oil (SO) or estradiol valerate (5 mg; EV) injected on Days 11 through 14 of the estrous cycle and an intrauterine injection of saline (5 ml; SA) or prostaglandin F2 alpha (50 micrograms; PGF) on Day 14. Peripheral blood samples were collected for 120 min postinjection and analyzed for 15-keto-13,14-dihydro-PGF2 alpha (PGFM). PGFM concentrations were lower in EV than SO gilts (438 vs. 844 pg/ml; p less than 0.05). There was heterogeneity of regression between EV and SO gilts (p less than 0.01), with EV gilts having a slower release of PGF from the uterine lumen into the vasculature. Prostaglandin F2 alpha did not increase mean PGFM concentrations (p greater than 0.10), but resulted in an altered temporal pattern of PGFM (p less than 0.05) compared to SA gilts. There was an interaction between the two treatments over time, with EV-PGF gilts demonstrating a slower, more gradual release of PGFM than SO-PGF gilts. To test whether prostaglandins of the E series were involved in this mechanism, gilts were assigned to two 4 X 4 latin squares balanced for residual effects and treated with saline or flunixen meglumine (Banamine). Each gilt was treated with four PGE:PGF infusion sequences (SEQ) in each uterine horn: phosphate-buffered saline (PBS; PBS-SEQ), PGE1 (50 micrograms), PGE2 (50 micrograms), and PGE1 (25 micrograms) + PGE2 (25 micrograms) (PGE-SEQ), with each infusion followed 15 min later by PGF (25 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)

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Skin graft survival in the uterine lumen of ewes treated with progesterone.

An experiment was conducted to determine the effect of progesterone on survival of skin transplants placed in the uterine lumen of ovariectomized ewes. Animals were treated for 30 days with either a corn oil vehicle (n = 4) or progesterone at 50 (n = 3) or 200 mg/day (n = 3). An autograft and allograft were then placed in each uterus, and treatments were continued for an additional 30 days before grafts were examined for survival. All autografts were present 30 days after grafting and most appeared healthy upon histological examination. Allografts placed into the uterine lumen of progesterone-treated ewes were present 30 days after grafting but were necrotic in histological appearance. Allografts placed within the uterus of corn oil-treated ewes were completely resorbed. Uterine secretions that accumulated in the uterine lumen were examined for inhibitory effects on [3H-methyl]thymidine incorporation by lymphocytes stimulated with phytohemagglutinin (PHA). The total amount of immunosuppressive activity in the uterine lumen was greater (P less than 0.05) for progesterone-treated ewes than for corn oil-treated ewes. Concentrations of progesterone in uterine secretions of progesterone-treated ewes ranged from 0.3 to 3.4 ng/ml. Thymidine incorporation into PHA-stimulated lymphocytes was not affected by in vitro treatment with up to 500 ng/ml of progesterone. In conclusion, progesterone delayed resorption of skin allografts placed in the uterine lumen. Results are consistent with the hypothesis that progesterone mediated this effect by stimulating the secretion of immunosuppressive substances into the uterine lumen.

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Proteins secreted by the sheep conceptus suppress induction of uterine prostaglandin F-2 alpha release by oestradiol and oxytocin.

In Exp. I, 0.5 mg oestradiol or vehicle (0.5 ml absolute ethanol + 0.5 ml 0.9% NaCl) was injected i.v. at 08:00 h on Day 14 (onset of oestrus = Day 0). Blood samples were obtained via a jugular catheter at 30 and 1 min before oestradiol and every 30 min for 10 h afterwards. Plasma was obtained and assayed for 15-keto-13,14-dihydro-PGF-2 alpha (PGFM) by radioimmunoassay. Before oestradiol, PGFM basal values were higher (P less than 0.01) in pregnant (N = 10) than nonpregnant (N = 6) ewes (193 +/- 30 vs 67 +/- 8 pg/ml). However, at 4-10 h after oestradiol, pregnant ewes (N = 5) had less variable (P less than 0.01) PGFM values than did nonpregnant ewes (N = 5). In Exp II, conceptus secretory proteins (CSP) were obtained by pooling medium from cultures of Day-16 sheep conceptuses (N = 40). Ewes received 750 micrograms CSP + 750 micrograms plasma protein (N = 6) or 1500 micrograms plasma protein (N = 6) per uterine horn at 08:00 h and 18:00 h on Days 12-14. All ewes received 0.5 mg oestradiol at 08:00 h on Day 14 and blood samples were collected as in Exp. I and assayed for PGFM. On Day 15, 3 ewes in each group received 10 i.u. oxytocin and 3 received saline i.v. at 08:00 h and blood samples were taken continuously from 10 min before to 60 min after treatment. Mean PGFM response to oestradiol was suppressed (P = 0.05) in CSP- vs plasma protein-treated ewes (371 +/- 129 vs 1188 +/- 139 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

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Role of conceptus secretory products in establishment of pregnancy.

Conceptuses produce steroids, prostaglandins, proteins and possibly other unidentified agents which may play a role in the establishment and maintenance of pregnancy. A key event in this process is protection of the corpus luteum (CL) from the luteolytic activity of prostaglandin (PG) F-2 alpha of uterine origin. Oestrogens produced by the pig conceptuses between Days 11 and 16 appear to exert an antiluteolytic effect resulting in the sequestering of PGF-2 alpha within the uterine lumen. Failure of the pregnant uterus to release PGF-2 alpha in an endocrine fashion, therefore, allows for maintenance of CL function. Conceptuses of sheep and cattle produce proteins which, when introduced into the uterine lumen of nonpregnant ewes and cows, suppress the ability of oestradiol and oxytocin to stimulate uterine production of PGF-2 alpha. These conceptus secretory proteins appear to exert an antiluteolytic effect by inhibiting uterine production of luteolytic amounts of PGF-2 alpha. The horse conceptus produces both oestrogens and proteins during early pregnancy when uterine production of PGF-2 alpha is suppressed. Co-culture of horse endometrium and conceptus inhibits endometrial production of PGF-2 alpha. Conceptuses of pigs, sheep and cattle undergo elongation to achieve apposition between trophectoderm and endometrium but the horse embryo migrates rapidly and consistently throughout the uterus to achieve endometrial contact.

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Proteins secreted by day-16 to -18 bovine conceptuses extend corpus luteum function in cows.

Corpus luteum function, interoestrous interval and spontaneous uterine PGF-2 alpha (PGF) production were evaluated in 9 cyclic Holstein cows (3/group) after intrauterine injections of pooled conceptus secretory proteins, 5 beta-pregnan-3 alpha-ol-20-one, or homologous serum proteins on Days 15.5 through 21 after oestrus. A significant extension of corpus luteum lifespan and interoestrous interval were detected in cows treated with conceptus secretory proteins compared to the other 2 groups. CL lifespan and interoestrous interval were not different (P greater than 0.25) between 5 beta-pregnan-3 alpha-ol-20-one and control groups. Evaluation of spontaneous PGF responses suggested that proteins synthesized and secreted by the bovine conceptus accommodate luteal maintenance during early gestation via an attenuation of endometrial PGF production.

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Role of uteroferrin in placental iron transport in swine: relationship between uteroferrin levels and iron deposition in the conceptus during gestation.

This study was to examine the relationship between uteroferrin and Fe, and Fe and Cu in the fetal pig. In Exp. 1, conceptus tissues and fluids were obtained on d 30, 45, 60, 75 and 90 of gestation for Fe and Cu analyses. In fetus minus liver, total Fe and Cu increased constantly between d 30 and 90, but Fe and Cu concentrations (microgram/g dry tissue) both decreased between d 30 and 45 and then remained relatively constant to d 90. For fetal liver, total Fe increased from d 30 (27 micrograms) to d 90 (3,222 micrograms), as did total Cu (14 micrograms on d 30 to 960 micrograms on d 90). Fetal liver Fe concentration (microgram/g dry tissue) decreased from d 30 (1,021) to d 60 (472) and then increased to d 90 (1,082), whereas Cu concentration increased between d 30 (537) and 60 (830) and then decreased between d 60 (471) and 90 (329). In allantoic fluid, both total Fe and Cu increased between d 30 and 60 and then decreased to d 90. Data from this study indicated a close temporal relationship between Fe and Cu in the fetal tissues and fluids examined. In Exp. 2, the relationship between Fe and uteroferrin in fetal tissues and fluids was studied. Uteroferrin, measured indirectly by acid phosphatase activity and Fe in fetal tissues and fluid underwent closely related temporal changes between d 30 and 112 of gestation. Changes in total Fe and Fe concentration during gestation were similar to those described for Exp. 1 in fetus minus liver, fetal liver and allantoic fluid. In addition, total Fe and Fe concentration in placental and endometrial tissues were analyzed. It was concluded that uteroferrin provides a major source of Fe in endometrial secretion and that it may be stored in placental and endometrial tissues. The relationship between Fe and Cu in conceptus tissues and erythropoiesis also is discussed.

Acid Phosphatase↗

Effect of number of conceptuses on maternal hormone concentrations in the pig.

This study examined the effect of number of conceptuses on maternal concentrations and profiles of estrogen sulfate, estrone, estradiol-17 beta, progesterone and prolactin in gilts. Estradiol-valerate injections were used to induce pseudopregnancy (O conceptuses; n = 5) and oviduct ligation or no treatment were utilized to obtain pregnant gilts with 4 to 7 (n = 4), or 8 to 11 (n = 4) conceptuses, respectively. Blood samples were collected every 10 d from d 10 through 110 of pregnancy or pseudopregnancy. At 110 d after onset of estrus, all gilts were slaughtered and numbers and(or) weights of fetuses, corpora lutea, placentae and the empty uterus were determined. Concentrations of estrogen sulfate and estrone, but not progesterone or prolactin, were associated with fetal number, total fetal weight, total placental weight or empty uterine weight. In contrast, only progesterone was highly correlated with number of corpora lutea. Results suggest that most conjugated estrogen, estrone and estradiol were of fetal-placental origin, whereas little, if any, placental production of progesterone or prolactin occurred. Increases in estrogen sulfate and estrone concentrations were observed at gestation d 30 and from d 70 to 100. The latter increase coincides with previously established increases in the rate of maternal mammary development and fetal growth.

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Ultrastructural changes in porcine mammary tissue during lactogenesis.

Ultrastructural changes occurring in porcine mammary tissue were characterised between Day 90 of pregnancy and Day 4 of lactation. Porcine mammary tissue on Day 90 of pregnancy was composed of alveoli which contained negligible to moderate amounts of secretion. Epithelial cells of these alveoli were relatively undifferentiated. The appearance and distribution of cellular organelles suggested that mammary epithelial differentiation had been initiated by Day 105 of pregnancy in the pig. A further increase in intracellular lipid droplets and granular endoplasmic reticulum suggested that differentiation had progressed by Day 112. On the day of parturition, secretions within the alveolar lumina assumed the appearance of normal milk (as opposed to colostrum) and the epithelia displayed a distinct cellular polarity characteristic of lactating mammary tissue. By Day 4 of lactation, differentiation of epithelial cells appeared to be complete, with dilated cisternae of the granular endoplasmic reticulum and with numerous secretory vesicles. Elongated microvilli were present and numerous cells contained lipid droplets which were being extruded into the lumina. Data from this and previous studies indicate that lactogenesis in the pig occurs in two stages. Stage 1 occurs between Days 90 and 105 of pregnancy, and Stage 2 between Days 112 of pregnancy and early lactation when the predominant feature is active milk secretion.

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Role of uteroferrin in transplacental iron transport in the pig.

The pig possesses a noninvasive, diffuse type of epitheliochorial placentation in which the blood supply of the mother is well separated from the absorptive surface of the chorion, a feature that must complicate the movement of nutrient molecules across the placenta. Evidence is presented that a protein synthesized and secreted by the glandular epithelial cells of the maternal uterus of the pig is involved in iron transport to the fetus. This protein, uteroferrin, is induced by progesterone; is purple, which results from an unusual iron center; and possesses acid phosphatase activity. Secreted uteroferrin is taken up by specialized chorionic epithelial cells located in domed structures, called areolae, overlying the mouth of each uterine gland. Uteroferrin then enters the placental venous drainage and its iron is efficiently incorporated into fetal hemoglobin. It is taken up by the fetal liver or cleared by the kidney. The liver is the main site of erythropoiesis in the fetus. From the kidney uteroferrin enters the allantoic sac where it exchanges its iron with fetal transferrin. The rate of uteroferrin biosynthesis in the uterus and its rate of metabolism in the fetus can theoretically provide sufficient iron for the needs of pregnancy, at least until around day 70 of the 115-day gestation. Uteroferrin and transferrin, the iron transport protein of plasma, appear to be unrelated proteins.

Acid Phosphatase↗

The type 5, acid phosphatase from spleen of humans with hairy cell leukemia. Purification, properties, immunological characterization, and comparison with porcine uteroferrin.

The spleens of patients with hairy cell leukemia contain high levels of a tartrate-insensitive, cationic, acid phosphatase (the human Type 5 isozyme). This phosphatase has been purified by a procedure which involves only two chromatographic steps: CM-cellulose chromatography and immunoaffinity chromatography on sheep antibodies generated against porcine uteroferrin. Uteroferrin is an abundant iron-containing acid phosphatase that can be recovered readily from porcine uterine secretions. Like uteroferrin, the purified human Type 5 phosphatase is a glycoprotein of molecular weight about 34,000. It contains two atoms of iron/molecule. The human phosphatase and uteroferrin also resemble each other closely in electrophoretic mobility, substrate specificity, and response to a variety of activators and inhibitors. Mouse monoclonal antibodies have been raised to uteroferrin and to the human Type 5 phosphatase. Three monoclonal antibodies which bind with high affinities to distinct sites on the uteroferrin molecule also recognize the human spleen enzyme, but bind to it with much lower affinity. These antibodies also recognize cationic acid phosphatases purified from bovine and rat spleens. A monoclonal antibody raised against the human enzyme, but selected for binding to uteroferrin, appears to recognize a relatively conserved site on all four phosphatases. We conclude that the human Type 5 isozyme belongs to a growing class of structurally related, iron-containing acid phosphatases which includes the iron-transport protein, uteroferrin.

Acid Phosphatase↗