Histogenesis of the ovine uterus.

Reproductive tracts from fetal (d 55 to 150) and neonatal (d 9 to 3 mo) lambs were examined by light microscopy in order to describe ovine uterine histogenesis. Morphologically, d-55 and -60 fetal uteri were bipartite, though characteristic external cornual morphology was not apparent until d 100 to 110. Histologically, lumina of d-55 and -60 fetal uteri were tubular and smooth with no indication of caruncular or glandular areas. In d-90 to -100 fetal uteri, luminal clefts were visible along the mucosal surface and a band of eosinophilic, elongated, smooth muscle-like cells was distinguishable. By d 100 to 110, nodular and internodular areas were clearly defined as luminal clefts deepened. Expansion of deep internodular areas, parallel to the luminal nodular surface, progressed in fetal uteri from d 118 to 150. Slight invaginations along deep internodular areas were visible in d-135 fetal uteri and were regular features of d-150 fetal uteri. In contrast, shallow, slightly coiled simple tubular glands were visible in the endometrium of internodular (intercaruncular) areas in a d-9 neonatal uterus. Older neonatal uteri (d 26 to 3 mo) contained coiled tubular glands which extended to the myometrium. Data indicate a systematic pattern of ovine uterine histogenesis involving dynamic morphogenetic alterations, especially between d 80 to 130 of fetal life. The observation that uterine glands were absent in fetal uteri but present in neonatal uteri suggests that glandular induction must occur during the periparturiet/neonatal period.

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.

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.

Ovarian function during the estrous cycle of the cow: ovarian blood flow and progesterone release rate.

To study the function of the corpus luteum (CL) through its major secretory product, progesterone (P4), catheters were inserted into the carotid artery (via the facial artery) and the ovarian vein (n = 12), and electromagnetic flow transducers were placed around the ovarian artery in cycling Angus and Hereford cows (n = 6). Blood samples were taken four times daily (at 0600, 1200, 1800 and 2400 h) and ovarian blood flow (OBF) was monitored for 60 min immediately after each blood sampling. After chromatography, P4 was measured by radioimmunoassay. The P4 concentrations in the ovarian vein (OP4) were correlated with day of the estrous cycle (r = .25; P less than .05) and were higher during the morning hours (P less than .05). Arterial progesterone (SP4) was correlated to OP4 (r = .24; P less than .05) and day of the cycle (r = .35; P less than .05). The OBF changed among days (P less than .05). The highest rates were noted during luteal maturation (23 ml/min; SE = .09) and the lowest were noted with the demise of the CL (SP4 less than 1 ng/ml) and approach of estrus (8 ml/min; SE = .07). The OBF was correlated with SP4 (r = .24; P less than .05), although no within-day trends were noted. Exogenous estrone (6 mg) administered via jugular vein decreased OBF within 30 to 45 min, but similar injections of P4 (up to 100 mg) had no effect. Progesterone release (P4R) from the ovary [(OP4 - SP4) x OBF] was higher in the morning hours (P less than .05). The P4 concentration (OP4, SP4) and release (P4R) exhibited wide variations among and within days. The changes in OP4 and P4R were both good indicators of CL development, maturation and regression, as associated with SP4 changes. Oxygen (O2) and carbon dioxide (CO2) concentrations monitored in the carotid artery and ovarian vein indicated that the ovary with the CL was not limited in O2 availability or CO2 removal during periods of low blood flow or high secretion of P4.

Method for obtaining ovine uterine secretions from unilaterally pregnant ewes.

Development of the ovine conceptus was confined to the uterine horn ipsilateral to the corpus luteum (CL) by placing a ligature around that uterine horn at a point near the uterine body on day 5 of pregnancy. On day 140 of gestation, seven of 10 ewes were still pregnant and from 21 to 815 ml of uterine fluid (488 +/- 94 ml, X +/- SEM) were collected from the nongravid uterine horn. Total recoverable protein (X +/- SEM) was 13.4 +/- 3.4 grams. Polyacrylamide gel electrophoresis of the reduced proteins in presence of sodium dodecyl sulfate indicated that protein composition of uterine fluid was distinct from that of colostrum, serum, amniotic fluid, and allantoic fluid, and revealed the presence of two major polypeptides with molecular weights of about 57,000 and 58,500, respectively, plus numerous other minor components. Gel filtration on columns of Sephadex G-200 and Sepharose CL-6B suggested that these polypeptides formed a series of aggregates of high molecular weight when kept under nonreducing conditions. Glucose (.18 +/- .03 mg/ml), but not fructose, was present in uterine fluid. In addition, high levels of prostaglandin F (451.4 +/- 83.3 ng/ml) were present.

O2 delivery to the pregnant uterus: its relationship to O2 consumption.

Normal sheep were studied at intervals of 3-5 days during the last weeks of pregnancy in order to evaluate variability in rate of O2 consumption (QO2) of the uterus in relation to several variables involved in delivery of O2 to the organ. Among-animal differences of uterine QO2 were statistically significant and directly related to birthweight of the lamb. Among-animal differences of uterine blood flow (UBF) and uterine arteriovenous O2 content difference [C(a-v)O2] also were statistically significant, though neither was related to birthweight, presumably since they tended to vary inversely with one another. In a given ewe relative magnitude of UBF and of C(a-v)O2 was related to maternal arterial O2 content (CaO2), day of pregnancy, and whether the animal carried singlets or twins. Variability in QO2 was most closely related to UBF, although its relations to C(a-v)O2 and CaO2 were significant also. These data suggest there are systematic relationships among variables involved in the delivery of O2 to the uterus of pregnant sheep.

[The effect of local anaesthetics on uterine blood flow and O2-consumption in pregnant sheep (author's transl)]. / Die Wirkung von Lokalanaesthetika auf Durchblutung und O2-Verbrauch des Uterus von schwangeren Schafen.

The local anesthetics bupivacaine, etidocaine, lignocaine and chloroprocaine were infused intravenously for 30 min to pregnant sheep, prepared for chronic studies. The amide compounds reached highere plasma concentrations than chloroprocaine. All local anaesthetics decreased uterine blood flow and O2 consumption without marked alterations of arterial or uterine venous blood gases. These changes were within the wide physiological range of variation, which was established in controls during 24 h. The findings may be of significance during paracervical block or pathological states of UBF or fetal homeostasis.

Uterine blood flow, oxygen consumption, and maternal plasma estradiol and progestins following fetal death.

Fetuses of 42 near-term sheep were killed while they were in utero. Uterine blood flow, oxygen consumption, A-V O2, and maternal arterial plasma concentrations of estradiol and progestins were observed for the next 4 hours. There was an immediate (88 per cent) fall in oxygen consumption; blood flow decreased by 50 per cent within 30 minutes. Hormone concentrations changed, but only after 2 hours. Circulatory changes appeared to be related to local changes within the uterus, particularly to decomposition of the chorioallantoic membrane. This relationship was best seen in the experiments in which one of a set of twins was killed. The experiments are in accord with the theory that the rate of uterine blood is not directly related to acute changes in respiratory gases nor to plasma concentrations of certain hormones.

Paul Zweifel, pioneer fetal physiologist. A centennary tribute.

The demonstration by Paul Zweifel a hundred years ago (1876) that the fetus in utero consumes oxygen marks the beginning of the modern era of research on foetal physiology. The circumstances which led to the demonstration are reviewed, and its importance acknowledged anew as a tribute to Zweifel's many contributions to obstetrics and gynecology.

The circulating plasma volume of the foetal lamb as an index of its weight and rate of weight gain (g/day) in the last third of gestation.

In a series of foetal lambs weighing between 1,100 and 5,228 g, the circulating plasma volume was estimated by the dye dilution method, using Evans Blue, to test the possibility that the plasma volume could be used as an index of foetal weight in chronic studies. The data, analysed by the method of least squares regression, indicate that plasma volume and foetal weight are closely correlated (R-2 equals 0.922) and linearly so in the range of data studied. There was no evidence that the relation differed for singlets and twins. A single equation, Y equals 71.8 plus 10.11 X--where Y is the estimated weight and X the plasma volume, can be used to predict the weight from plasma volume in both. Some results of the application of the method in chronic studies are presented.