Two experiments were conducted to determine whether in ewes uterine concentrations of estrogen and progesterone receptors are affected by the presence of a conceptus or by the hormonal milieu associated with extremes in photoperiod to which ewes are exposed. In Exp.1, nine mature ewes were unilaterally ovariectomized by removing an ovary bearing the corpus luteum (CL). The ipsilateral uterine horn was ligated at the external bifurcation and a portion of the anterior ipsilateral uterine horn was removed and assayed for endometrial nuclear and cytosolic concentrations of estrogen receptor (ER) and progesterone receptor (PR) by exchange assays. After a recovery estrous cycle, ewes were bred to a fertile ram. On day 18 of gestation a 10 ml jugular blood sample was collected for measurement of serum concentrations of estradiol -17β (E₂) and progesterone by radioimmunoassay. Ewes were relaparotomized on day 18 and the remaining uterine tissue was removed. Endometrium from both the pregnant and nonpregnant uterine horn was assayed for nuclear and cytosolic ER and PR concentrations. Nuclear and cytosolic ER concentrations on day 10 of the cycle were greater than in endometrium of gravid and nongravid uterine horns on day 18 of gestation (p<.01). Endometrial nuclear PR levels were also greater on day 10 of the cycle than in the pregnant (p<.05) and nonpregnant horn (p<.01) on day 18 of gestation. There were no differences in nuclear and cytosolic ER and PR concentrations between the pregnant and nonpregnant uterine horn on day 18. Serum levels of E₂ and progesterone on day 18 of gestation were 16.56 ± 2.43 pg/ml and 1.74 ± 0.57 ng/ml, respectively. These data suggest that duration of exposure of the uterus to progesterone and(or) the presence of the conceptus causes a reduction in uterine concentrations of ER and PR. Further, an effect of the conceptus, if any, is exerted via a systemic route. In Exp. 2, ten mature ewes were bilaterally ovariectomized in early October. During the onset of the winter solstice (late December), a 10 ml blood sample was collected from five ewes for analysis of serum levels of E₂ and progesterone. Ewes were then laparotomized and approximately one-third to one-half of a uterine horn was removed and assayed for endometrial nuclear and cytosolic ER. The contralateral horn was ligated at the external bifurcation and 10 μg of E₂ in 3 ml of physiological saline was injected into the uterine lumen of the ligated horn. After 48 h, a jugular blood sample was collected for steroid analysis and a section of the E₂ treated horn was removed and assayed for endometrial cytosolic and nuclear ER. This procedure was repeated on the remaining five ewes during the height of the summer solstice (late June). Endometrial nuclear and cytosolic concentrations of ER prior to and after exogenous E₂ stimulation were similar during the winter and summer solstice (p>.05). However, treatment with E₂ increased endometrial nuclear and cytosolic concentrations of ER compared with those of the nonstimulated uterine horn during the winter and summer solstice (p<.05 for each). Serum levels of E₂ prior to luminal treatment of ewes with E₂ during the winter and summer solstice did not differ (16.55 ± 4.05 vs 16.00 ± 3.0 pg/ml, respectively, p>.05). Serum levels of E₂ 48 h after administration of E₂ did not differ among ewes at the winter and summer solstice (18.75 ± 2.4 vs 18.65 ± 1.65 pg/ml, respectively, p>.05). Serum levels of progesterone were basal (<0.10 ng/ml) and did not differ in ewes prior to and after E₂ treatment at the winter and summer solstice (p>.05). These data indicate that physiological factors and(or) hormones such as prolactin and melatonin secreted in response to extremes in photoperiod do not appear to influence uterine concentrations of ER in ovariectomized ewes. / Graduation date: 1991

Systemic injections of the neurosteroid progesterone (P) have been shown to improve cognitive, sensory and motor recovery after traumatic brain injury (TBI). Progesterone withdrawal (PW), however, increases the risk of ischemia, anxiety, seizure, and excitotoxicity. Given these side effects, it is possible that acute PW during recovery from TBI may retard the healing process. In this project, we investigated the effect of acute PW for short and long-term intervals, and optimized post-TBI P treatment through tapered P injections and slow-release implanted capsules. Male Sprague-Dawley rats received either frontal-bilateral cortical contusion injury or sham surgery. P-treated animals displayed increased anxiety in the elevated plus maze at the peak of acute withdrawal compared to tapered P doses or vehicle. Inflammation and apoptosis, as measured by TNF and #61537;, NF and #61547;B, and active caspase-3, among others, were decreased for all P-treated animals; these effects were further reduced with tapered treatment. Three weeks after injury, animals that received tapered P administration displayed fewer sensory deficiencies and increased motor activity. In addition, reducing the effects of acute PW increased the activity of HSP70 and BDNF while decreasing necrotic lesion size and reactive astrocyte staining, indicating increased neuroprotection. Finally, the beneficial effects of P administration after TBI were further enhanced through a steady-state release of P from a subcutaneously implanted silastic capsule. Compared to animals receiving a daily bolus through subcutaneous injections, capsule animals demonstrated decreased anxiety and edema. All P-treated animals, regardless of delivery method, had reduced inflammation and apoptosis compared to vehicle-treated animals. This system also serves as a model of steady-state intravenous P administration used in human clinical trials. In conclusion, all P treatment enhances both short and long term recovery after TBI. Acute PW, however, has a negative effect on both behavior and tissue recovery. At the peak of withdrawal, animals undergoing acute PW exhibit an increase in anxiety, sensory deficits, inflammation and apoptosis, and a decrease in locomotor activity, all of which are further exacerbated by injury. Tapered withdrawal enhances neuroprotection and plasticity, while a steady-steady application of P further decreases edema and the anxiogenic effects of withdrawal.

In cattle and sheep, a significant decrease in temperature has been noted prior to parturition. In the mare, similar temperature decreases have been documented, although results have been inconsistent when temperatures were taken rectally. One study reported a significant temperature decrease when using data from a radio transmitter inserted into the mare’s flank. The current study utilized nineteen Quarter Horse mares and one Thoroughbred mare, and was conducted from February to June 2006. Each mare had been previously implanted in the nuchal ligament with a microchip capable of reporting body temperatures. Blood collection and temperature recordings began 2 wk prior to each mare’s expected foaling date. Once the mare was estimated to be within 48 h of parturition, temperature was recorded every 3 h until parturition using both the microchip and rectal thermometer. Progesterone and estradiol 17-b were evaluated from daily blood samples from -10 to ± 5 d relative to foaling for determination of the relationship between these steroids and body temperature, time of foaling, birth weight and sex of foal. A significant decrease in rectal temperature (P < 0.05) was noted when the last temperature recorded was taken within 12h of parturition. Microchip data did not demonstrate any significant differences among readings before parturition. No significant difference was noted in the mean rectal temperature of all days relative to the sex of the neonate; however, microchip data showed mares carrying females to have a significantly (P < 0.05) higher mean rectal temperature of all days. Sex of the foal was not shown to be related to maternal concentrations of either progesterone or estradiol 17- b. A direct significant correlation between temperature and maternal plasma concentrations and progesterone and estradiol 17-b was found.

A homogeneous group of thirty-one crossbred ewes was used to determine the effect of administering a progesterone Controlled Intravaginal Drug Releasing Device (CIDR) on circulating levels of progesterone in the subsequent cycle following CIDR removal. Circulating progesterone levels were determined for each ewe through daily blood collection via jugular venipuncture. Each ewe underwent a pretreatment 25 day sampling period (Period 1), a 12 day treatment period characterized by the presence of the CIDR (Period 2), and another 25 day sampling period following CIDR removal (Period 3). During the initial period of the study, progesterone levels in peripheral circulation changed (P < 0.0001, effect of day) in accordance with stage of the estrous cycle and were elevated during the luteal phase. In the second period of the study, progesterone levels were elevated (P < 0.0001) in ewes due to exogenous progesterone from the CIDR device (Period 1 versus Period 2: 1.3 ± 0.1 ng/ml versus 2.4 ± 0.1 ng/ml, respectively). After withdrawal of the CIDR in the third period of the study, circulating progesterone levels were not (P > 0.10) different from those observed in the initial period of the study (Period 1 versus Period 3: 1.3 ± 0.1 ng/ml versus 1.4 ± 0.1 ng/ml, respectively). Data collected in this study revealed that treatment with exogenous progesterone via CIDR for a 12- day treatment period does not influence circulating levels of progesterone in subsequent estrous cycles.

The peri-implantation period in mammals is critical with respect to survival of the conceptus and establishment of pregnancy. During this period of pregnancy, reciprocal communication between ovary, conceptus, and endometrium is required for successful implantation and placentation. Therefore, studies were conducted to indentify and characterize novel endometrial genes important for implantation and conceptus development in the ovine uterus. The first and second studies defined the uterine expression of seven members of the cathepsin (CTS) family of lysosomal proteases, and a secreted inhibitor of CTSL called cystatin C (CST3) during the peri-implantation period. In addition, regulation of CTS and CST3 by progesterone (P4) and interferon tau (IFNT) was evaluated. CTSL was the most abundant CTS in the ovine ovine uterus and was also coordinately expressed with CST3 in the endometrial epithelia and conceptus trophectoderm. CTSL and CST3 were found to be novel P4-induced and IFNT-stimulated genes in the luminal epithelial cells of the ovine endometrium. The third study identified radical S-adenosyl methionine domain containing 2 (RSAD2) and interferon-induced with helicase C domain 1 (IFIH1) in the ovine uterus. Results of this study indicated that IFNT induces RSAD2 and IFIH1 in a P4-independent manner in the stroma, immune cells, and glands of the ovine endometrium. These two genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation. The fourth study characterized endometrial expression of stanniocalcins (STC) during pregnancy. STC1 appeared in the endometrial glands on Day 18 of pregnancy, increased from Days 18 to 80, and remained abundant through Day 120 of gestation. In addition, this study demonstrated that STC1 is induced by P4 and increased by placental hormones, such as placental lactogen (CSH1) and growth hormone (GH), in the ovine endometrial glands. Collectively, these studies identified genes that are expected to be critical to unraveling the mechanism(s) of reciprocal fetal-maternal interactions required for successful implantation and pregnancy. A more complete understanding of these genes will be important for developing therapeutic strategies to prevent, treat and/or diagnose infertility in domestic animals and humans, because they are biomarkers of P4 and/or IFN effects.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2009. / Härtill 4 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains viii, 160 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 132-159).

Haemostasis is an important aspect in neurosurgical operations for the achievement of good outcome. Bipolar coagulation is an extensively used haemostatic technique in modern neurosurgery but it may also cause iatrogenic brain trauma due to thermal injury. Published studies on coagulation-induced brain injury on a histological level are, however, limited. The present study aimed at investigating the extent of inflammatory and glial responses caused by different settings of bipolar coagulation using an animal model. It also investigated whether and how pre-operative treatment with dexamethasone or progesterone, both known to have neuro-protective effects, would modulate gliosis and macrophage infiltration induced by bipolar coagulation. The study consisted of two parts. The first part investigated the astrocytic and macrophage responses after bipolar coagulation at different power settings. 45 Sprague-Dawley rats received craniotomy, followed by bipolar coagulation at different power output settings (mock operation as control, 20W and 40W) over the rat cortex for a standardized duration of two seconds. On day 3, day 7 and day 28, brain sections were assessed by immunohistochemical staining for GFAP (astrocytes) and ED1 (macrophages). Quantification of outcome by random field cell counting under light microscopy was performed. The second part of the study used another 45 male Sprague-Dawley rats, divided into three treatment groups: Group 1 received the vehicle agents only (Control); Group 2 received progesterone 20mg/kg; Group 3 received dexamethasone 1 mg/kg. All treatments were given intraperitoneally two hours before craniotomy. The animals received bipolar coagulation at 40W for a standardized duration of two seconds. On day 1, 3 and 7, brain sections were assessed by immunohistochemical staining for GFAP and ED1. Quantification of outcome by random field cell counting under light microscopy was performed. T2-weighted magnetic resonance imaging for the animals on day 3 was also performed. The results showed that bipolar coagulation was associated with significant glial and inflammatory responses that correlated with power output. Progesterone and dexamethasone were both effective in reducing the glial hypertrophy and macrophage infiltration associated with bipolar coagulation. Dexamethasone had an additional advantage of reducing brain oedema and cavity formation. The findings suggested that progesterone and dexamethasone could be further explored as potential protective and/or remedial agents for bipolar coagulation-induced brain trauma sustained during neurosurgical procedures. / published_or_final_version / Surgery / Master / Master of Research in Medicine

No description available.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 115-146) Also available in print.