Biomedical subjects

S E Shideler

Publications and source records attributed to S E Shideler.

At least 19 recordsLinked to original sources

PubMed2006

Effect of porcine zonae pellucidae immunisation on ovarian follicular development and endocrine function in domestic ewes (Ovis aries).

Domestic ewes (Ovis aries) were immunised with porcine zonae pellucidae (pZP) or pZP conjugated to keyhole limpet haemocyanin (KLH) in adjuvant(s) to examine the feasibility of the species to serve as a model for further development of pZP-based vaccines in ungulates. Two immunisation groups were employed, with a third group receiving only adjuvant (n = 5 per group). Early in the study, oestrous activity was monitored by the use of a vasectomised ram fitted with a marking harness. Eventually, ewes were exposed to an intact ram for breeding. In addition, weekly serum and every-other-day faecal samples were collected to measure pZP antibodies and progesterone metabolite concentrations respectively. At the conclusion of the study, fecundity was established, and ovarian tissue was examined. Ewes immunised against pZP : KLH with adjuvant produced minimal antibody absorbance levels, displayed normal oestrous cycles, became pregnant upon introduction of the intact ram and exhibited normal ovarian histopathology. Ewes immunised against pZP with adjuvant produced high antibody absorbance levels, were acyclic following primary immunisation and were infertile. Examination of the ovarian tissue revealed atrophic changes that included: (1) the absence of growing follicles; (2) significant reduction in the number of primordial follicles; and (3) the presence of abnormal granulosa cell clusters lacking oocytes. Antisera displayed immunoreactivity to the major components of pZP, and immunohistochemical labelling of ovarian tissue showed specificity to the ZP. These data are the first generated in an ungulate species showing deleterious effects of pZP immunisation on folliculogenesis and oestrous cyclicity.

Adjuvants, Immunologic↗

PubMed2003

Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta.

This study was designed to test the hypothesis that basal estrone conjugate (E1C) profiles do not accurately detect ovarian function when ovarian estrogen production is low or absent. We employed surgical removal of active ovaries from laboratory rhesus macaques to simulate an acute decline in ovarian estrogen production. In the first experiment, urine samples collected prior to and following ovariectomy (Ovx) were subjected to high-performance liquid chromatography (HPLC) separation. Eluates were then assayed for E1C immunoreactive components. The results indicated a modest decrease in total immunoreactive polar conjugates following ovariectomy, with no substantial change in the overall retention profile. In the second experiment, estradiol (E2) cypionate injections were used to replace the E2 component of ovarian estrogen production in the treated (Tx) group, while the control group (C) received only vehicle. Urine samples were hydrolyzed and individual estrogens were separated by celite chromatography prior to immuno-assay. Both the Tx and C groups exhibited similar urinary excretion levels of estrone (E1), E2, and E1C prior to Ovx (Pre-Ovx) and after Ovx (Post-Ovx), but there were significant differences between groups after treatment (Post-Tx). Significant differences were observed in the Tx group's excretion of E1, E2, and E1C in the Pre- vs. Post-Ovx samples and in the Post-Ovx and Post-Tx samples. The C group also showed the expected significant differences in the Pre- vs. Post-Ovx samples, as well as in the Pre-Ovx and Post-Tx samples. The results indicate that the use of E1C measurements is clearly a suitable method for monitoring ovarian function in intact, cycling animals, but urinary E2 measurements are required to verify loss of follicular activity.

Animals↗

PubMed2002

Excretion and measurement of estradiol and progesterone metabolites in the feces and urine of female squirrel monkeys (Saimiri sciureus).

The first objective of the present study was to determine the metabolic form and rate of excretion of ovarian hormone metabolites in the urine and feces of female squirrel monkeys injected with radiolabeled progesterone (Po) and estradiol. The major portion of the urinary metabolites of both hormones was excreted within 16-24 hr post-injection. Estrogen and Po isotopes in feces exhibited an excretion peak at 16 hr post-injection. The majority of recovered radiolabel of both hormones was excreted in feces. Chromatographic separation of fecal extractions indicated that the major estrogen metabolites in feces are in the free as opposed to the conjugated form. The radioactivity and immunoreactivity for estrone and estradiol (E(1) and E(2), respectively) in eluates of fecal samples subjected to celite co-chromatography indicated that both free E(1) and E(2) exist as excretion products in the feces of female squirrel monkeys. The major radioactive peaks for Po metabolites showed peaks in the elution profile at or very near the Po standard, and corresponded with the celite co-chromatography elution profile of Po standard when subjected to enzyme immunoassay (EIA). The second objective was to validate the application of EIA systems to measure fecal metabolites. Reproductive events of one female squirrel monkey across one annual reproductive cycle are described using the endocrine profile generated from fecal steroid assays. Examination of this profile confirmed that longitudinal fecal sampling and steroid hormone metabolite measurement in feces was not only feasible and practical, but accurately detected known reproductive events as well.

Animals↗

PubMed2002

Use of porcine zona pellucida (PZP) vaccine as a contraceptive agent in free-ranging tule elk (Cervus elaphus nannodes).

The potential for the application of porcine zona pellucida (PZP) immunocontraception in wildlife population management has been tested over a 15 year period and promises to provide a useful wildlife management tool. These studies have provided evidence indicating that the use of PZP immunocontraception in wildlife: (i) is effective at both the physiological and population level (Liu et al., 1989; Kirkpatrick et al., 1996; Turner et al., this supplement); (ii) is deliverable by remote means (Kirkpatrick et al., 1990; Shideler, 2000); (iii) is safe in pregnant animals (Kirkpatrick and Turner, this supplement); (iv) is reversible (Kirkpatrick et al., 1991; Kirkpatrick and Turner, this supplement); (v) results in no long-term debilitating health problems (Kirkpatrick et al., 1995; Turner and Kirkpatrick, this supplement); (vi) has no implications for passage through the food chain (Harlow and Lane, 1988); and (vii) is reasonably inexpensive (J. F. Kirkpatrick, personal communication). This report presents the results of a 5 year study in tule elk (Cervus elaphus nannodes), 3 years of which were on the application of PZP immunocontraception to an expanding elk population living in a wilderness area of Point Reyes National Seashore in Marin County, CA, where hunting is not allowed and culling is not publicly acceptable.

Animals↗

PubMed2001

Noninstrumented enzyme-linked immunosorbant assay for detection of early pregnancy in macaques.

A practical, noninstrumented enzyme-linked immunosorbant assay (NELISA) for the measurement of urinary monkey chorionic gonadotropin (mCG) has been developed for the detection of early pregnancy in macaque monkeys for use in both the laboratory and the field. Five rhesus monkeys (Macaca mulatta) and six crab-eating monkeys (Macaca fascicularis) were tested for the presence of mCG in urine on gestational days (GDs) 12 to 35. The mCG NELISA detected pregnancy as early as GD 14, with an average earliest detection at GD 16.5 +/- 1.4 (n = 11). Out of 90 tests, 27 false-negative and zero false-positive tests were obtained, for an accuracy of 70.0%. Without the aid of a spectrophotometer, the presence of mCG in pregnant monkey samples was indicated by a dark green color change. Nonpregnant monkey urine samples, on the other hand, exhibited no color change. These findings suggest that the simple, economical, and reliable urinary mCG NELISA may be useful for diagnosing early pregnancy in these and related species. Because capture and restraint are unnecessary for collecting urine samples, the mCG NELISA has widespread potential for confined and free-ranging animals.

Animals↗

PubMed2001

Fecal analysis of ovarian cycles in female black-handed spider monkeys (Ateles geoffroyi).

An enzyme immunoassay (EIA) was applied to characterize the reproductive endocrinology of adult female black-handed spider monkeys (Ateles geoffroyi). Analysis of paired urine and fecal samples, collected from two females housed at San Diego Zoo, confirmed that the EIAs employed provided quantitative measurements of ovarian sex steroid hormones. Fecal metabolite levels were significantly correlated with those in urine, confirming that feces are a valid source of steroid metabolites in this species. The excretion of these metabolites in feces lagged urinary excretion by 1-2 days. The ovarian cycle profiles of the two captive females and five free-ranging females are comparable, with an average length of approximately 20-23 days. Cyclical bleeding, as previously reported, was observed in one of the two captive females. Pregnancy was detected in four free-ranging females, and early fetal loss for one female was indicated by hormonal data.

Animals↗

PubMed2001

Estrogen and progesterone metabolites and follicle-stimulating hormone in the aged macaque female.

The study presented characterizes the ovarian and pituitary function of the aged female macaque through a complete annual reproductive cycle to compare hormone dynamics during the human and nonhuman primate menopausal transition. Data collected over an entire year from aged macaque females indicated that urinary FSHbeta subunit baseline levels statistically significantly increased in females after age-related abnormal menstrual cycles occurred. These abnormal cycles were followed by anovulation and complete cessation of follicular activity. No statistically significant difference in urinary FSHbeta subunit levels was seen between females that exhibited year-round normal ovarian cycles and those that exhibited seasonal ovarian cycles followed by an interval of anovulation during the nonbreeding season. Basal urinary estrogen metabolite levels were not observed to decrease until ovarian cycles became abnormal and FSHbeta subunit levels began to rise. Early follicular phase circulating inhibin beta levels were statistically significantly reduced only when ovariectomized females were compared to the year-round normally cycling females. A statistically nonsignificant trend toward decreased inhibin secretion, however, was apparent in aged females with normal cycles, aged females with abnormal cycles, anovulatory aged females, and finally, ovariectomized females. Whereas decreased circulating levels of dehydroepiandrosterone sulfate showed a general decline over the 1-yr study period in all groups, they were lowest in the year-round normally cycling group, progressively higher in the normal-to-anovulatory group and abnormal-to-anovulatory group, and highest in the anovulatory group. Finally, the nonbreeding season was associated with the highest number of abnormal cycles, suggesting that onset of complete ovarian senescence in these study macaques was more likely to occur during that time (i.e., females were less likely to return to normal ovarian cycles the following breeding season and more likely to exhibit permanent ovarian quiescence).

Aging↗

PubMed1999

Application of an enzyme immunoassay for urinary follicle-stimulating hormone to describe the effects of an acute stressor at different stages of the menstrual cycle in female laboratory macaques.

An enzyme-linked immunosorbent assay (ELISA) for human urinary beta follicle-stimulating hormone (FSH) subunit was validated for use in the laboratory macaque (Macaca mulatta and Macaca fasicularis). This ELISA is based on the dissociation of the FSH heterodimer in urine and the subsequent measurement of the beta subunit as a representation of total urinary FSH. This assay was then used to describe the gonadotropin escape following ovarian senescence in post-menopausal macaques. In addition, the assay was used to observe the impact of an acute stressor on the pituitary-gonadal axis and how the impact of this stressor varies when experienced at different stages of the menstrual cycle. The study design involved the measurement of ovarian steroids and FSH in urine collected daily during a period of time when animals experienced a well-defined event on two occasions consisting of capture, restraint, and anesthesia. This unique study design was made possible by the ability to monitor both ovarian and pituitary function in the absence of confounding daily captures and restraint for blood collection. There was a high correlation between urinary FSH measured in macaques with the beta FSH subunit ELISA and serum FSH measured in paired blood samples by radioimmunoassay (n=39, r2=0.878, P<0.001) and the composite urinary FSH profile obtained from normal, premenopausal macaques exhibited the expected dynamics with a transient rise of FSH during the luteal-follicular transition as well as an acute rise of FSH at mid-cycle. This pattern was lost in castrate and post-menopausal monkeys in which FSH levels were significantly increased (P<0.0001) above those of intact males and young females, respectively. In the stress study, we found that stressors occurring during the luteal-follicular transition not only resulted in acute perturbations of FSH but also led to abnormalities in the subsequent menstrual cycle in 50% of the cases.

Animals↗

PubMed1997

Reproductive events of wild cotton-top tamarins (Saguinus oedipus) in Colombia.

Reproductive patterns of wild cotton-top tamarin (Saguinus oedipus) females located in La Reserva Forestal Protectora Serranía de Coraza-Montes de María in Colosó, Colombia, were examined using long-term behavioral observations and fecal steroid analysis. Using an enzyme immunoassay, we analyzed fecal samples for E1C and PdG. Comparisons of reproductive cycles of a reproductively active female and her daughters were made. An inhibition of ovarian cycles has been observed in daughters living in their families. However, daughters also exhibited normal ovarian cycling that subsequently resulted in pregnancy. Factors influencing the fertility are discussed as they relate to the reproductive strategies of wild cotton-top tamarin females.

Animals↗

PubMed1997

Characterization of the onset of menopause in the rhesus macaque.

The objective of this study was to assess ovarian activity in a cohort of aged female rhesus macaques. Menstrual records for 26 rhesus macaques ages 20-29 yr were evaluated over a 1-yr period, and daily urinary estrone conjugate (E1C) and pregnanediol-3-glucuronide (Hygeia [Hy]-PdG) levels were determined for 12 wk. Each animal was categorized as either pre-, peri-, or postmenopausal based on menstrual and hormonal data. Eleven animals (mean age 22.5 yr) were premenopausal, thirteen (mean age 24 yr) were perimenopausal, and two (mean age 29.5 yr) were postmenopausal. Hormone profiles for perimenopausal animals reveal prolonged follicular phases and/or a lack of patterned Hy-PdG dynamics. Breakthrough bleeding occurred in four of these perimenopausal animals. The postmenopausal animals were amenorrheic and exhibited low E1C levels (less than 10 ng/mg creatinine). The results of this study illustrate that the decline of ovarian function in female macaques during the third decade of life parallels the menstrual and hormonal events associated with the climacteric in women, and that menopause does occur in rhesus macaques.

Aging↗

PubMed1993

Simple extraction and enzyme immunoassays for estrogen and progesterone metabolites in the feces of Macaca fascicularis during non-conceptive and conceptive ovarian cycles.

A simple method for extracting ovarian steroids from feces is presented, together with enzyme immunoassay systems for measuring estrogen and progesterone metabolites. Small amounts of feces were combined in a 1:10 proportion with a modified phosphate buffer, shaken for 24 h, centrifuged, and decanted; the supernatant was directly measured for estrogen and progesterone metabolites by enzyme immunoassays. Serum estradiol and progesterone profiles were compared to urinary and fecal profiles in the same animals to determine the degree to which each reflected the ovarian events detectable in serum. The correlation coefficients for the relationship between serum, urinary, and fecal hormones for individual animal cycles were found to be statistically significant in every case but one, where the relationship between serum estradiol and urinary estrone conjugates was not significant. Urinary and fecal measurements were used to determine whether estrogen and progesterone metabolism and excretion varied within and between animals. Variation in unconjugated estrogen and progesterone metabolites was observed in the follicular phase, the luteal phase, and early pregnancy.

Animals↗

PubMed1993

Enzyme immunoassays for ovarian steroid metabolites in the urine of Macaca fascicularis.

In vivo studies using carbon 14 labeled estradiol (E2) and progesterone (Po) were performed to characterize the time course and metabolic fate of circulating E2 and Po. Co-chromatography of human, orangutan, and macaque luteal phase urine samples demonstrated the presence of a steroid conjugate peak in all three species that was identified as being androsterone and etiocholanolone glucuronides. An enzyme immunoassay for urinary metabolites of Po was developed subsequently for Macaca spp. using a monoclonal antibody that cross-reacted with both C-19 and C-21 metabolites.

Animals↗

PubMed1991

A prototype for ovulation detection: pros and cons.

A noninstrumented enzyme immunoassay for urinary estrone conjugates was adapted from an instrumented microtiter plate enzyme immunoassay assay. The end point of the assay was a color change from green to clear, which was visible to the unaided eye. The visible color change was adjusted to allow 80 ng/ml estrone conjugates (on the basis of a sample size of 6.5 microliters urine) to be distinguished from an infinite dilution without instrumentation. The evaluation of human urine collected from ovulatory ovarian cycles demonstrated that early follicular phase concentrations (35.9 +/- 6.8 to 79.4 +/- 14.7 ng/ml, n = 10) produced a dark-green color, whereas late follicular phase concentrations (162.9 +/- 20.1 ng/ml, n = 10) produced no color. Daily urine samples throughout 10 ovulatory ovarian cycles produced parallel profiles when compared to measurements of estradiol in paired blood samples. Complete analysis of the data indicated that ovarian follicular dynamics can be accurately monitored through the noninstrumented analysis of daily estrone conjugates in urine samples.

Adult↗

PubMed1991

Oestrous cycle of the North American bison (Bison bison) characterized by urinary pregnanediol-3-glucuronide.

An enzyme immunoassay for urinary pregnanediol-3 alpha-glucuronide (PdG) was evaluated for the indirect measurement of progesterone metabolites during the oestrous cycle and early pregnancy of uncaptured North American bison. Comparisons between plasma progesterone and urinary PdG, dose-response parallelism between the standard curve and diluted urine samples and high-performance liquid cochromatography revealed that PdG was a primary immunoreactive urinary metabolite of progesterone in bison. Urine samples were collected directly from the soil from 29 bison cows during the August rutting season and analysed for PdG. Eight bison cows demonstrated complete oestrous cycles ranging from 19 to 26 days (mean cycle length = 23.12 +/- 0.76 days) and behavioural oestrus among four of these cows correlated with PdG nadirs. Mean PdG nadirs were 63.62 +/- 21.61 ng/mg urinary creatinine (Cr) and mean peak midluteal values were 546.01 +/- 130.73 ng/mg Cr. Seven of eight became pregnant, indicating that bison exhibit a second seasonal oestrus. Eighteen other bison cows were pregnant prior to the beginning of the study and demonstrated non-cyclic increased PdG concentrations (greater than 200 ng/mg Cr) during the 30-day course of collection. Three cows ovulated and became pregnant during the 30-day collection period and then exhibited increasing urinary PdG concentrations. This report demonstrates that ovarian function in uncaptured bison can be monitored by means of urinary PdG and that both ovulatory cycles and early pregnancy can be detected.

Animals↗

PubMed1989

Ovarian-pituitary hormone interactions during the perimenopause.

To describe the hormone changes that occur at the onset of the perimenopause, daily urine and random blood samples were collected from 5 peri-menopausal women for 3 or 4 consecutive cycles. Estrone conjugate and pregnanediol-3-glucoronide concentrations were determined for urine samples. Circulating luteinizing hormone, follicle stimulating hormone, progesterone, estradiol and estrone concentrations were determined in serum samples. Two of the 5 women experienced irregular menstrual intervals during the study period. One of these subjects experienced a prolonged intermenstrual interval. Three other women exhibited apparently regular ovulatory menstrual cycles. The prolonged intermenstrual interval of one women exhibiting irregular menstrual intervals was associated with low urinary estrogen levels in the early follicular phase of the affected cycle, followed by increased gonadotrophin levels and increased estrogen levels that rose to exceed normal cycle concentrations by 2- or 3-fold. Increased estrogen levels were followed by declining gonadotrophin levels, minimal progesterone production, and, ultimately, vaginal bleeding. These data suggest that there are some forms of menstrual variability at the time of the perimenopause associated with lowered early follicular phase estrogen levels. Reduced negative feedback and subsequently increased gonadotrophin levels may have stimulated estrogen production which may have suppressed gonadotrophin secretion and lowered estrogen excretion, resulting in the observed oscillations between episodes of hypo- and hyperestrogenism.

Adult↗

PubMed1987

Comparison of serum estradiol to urinary estrone conjugates in the rhesus macaque (Macaca mulatta).

Paired urine and serum samples were collected daily during fourteen nonconceptive (7 females) and ten conceptive (9 females) ovarian cycles from a total of 12 female rhesus monkeys (Macaca mulatta). Daily urine samples were analyzed for concentrations of estrone conjugates (Ei Conj). Serum samples were evaluated for concentrations of estradiol (E2) and progesterone (P) by radioimmunoassay (RIA), and bioactive luteinizing hormone (bLH) and monkey chorionic gonadotropin (mCG) were analyzed by a mouse Leydig cell bioassay. Linear correlation (r) between urinary E1 Conj and serum E2 (r range = -0.176-0.948) during nonconceptive cycles aligned by the preovulatory E1 Conj peak (Day 0) improved when daily hormone values were realigned to account for an approximately 24-h delay in the excretion of hormonal metabolites in urine (r range = 0.465-0.967). Similarly, correlation between urinary E1 Conj and serum E2 during conceptive cycles aligned by Day 0 (r range = 0.300-0.824) improved when values were offset by 24 h (r range = 0.408-0.876). When conceptive cycles were compared to nonconceptive cycles, serum P levels were significantly elevated over nonconceptive levels by Day +12 (p less than 0.001), and urinary E1 Conj levels by Day +13 (p less than 0.02), whereas serum E2 and bLH were both significantly elevated by Day +14 (p less than 0.0006 and p less than 0.01, respectively). In both nonconceptive and conceptive cycles, urinary E1 Conj paralleled serum E2 and demonstrated incremental increases above baseline levels, which were greater than for serum E2.

Animals↗

PubMed1986

Monitoring gonadotropin-releasing hormone administration by measurement of urinary steroid conjugates.

The use of measuring urinary steroid conjugates in nontimed, randomly collected morning urine samples expressed as a function of creatinine concentration was assessed to monitor ovarian response to pulsatile administration of gonadotropin-releasing hormone in ambulatory patients. This method of evaluating ovarian steroid production provided a convenient, inexpensive, and noninvasive means of monitoring responses to gonadotropin-releasing hormone treatments and documents that clomiphene-resistant amenorrheic patients can be induced to ovulate with appropriate gonadotropin-releasing hormone therapy. Different ovarian responses in the same woman to similar doses and frequencies of gonadotropin-releasing hormone indicate that discrete adjustments of individual doses may be required to facilitate consistent ovulatory responses. The strategy presented here allows for subsequent gonadotropin-releasing hormone therapy in the individual patient to be determined by an objective and quantifiable ovarian response to an initial treatment.

Adult↗

PubMed1986

Monitoring ovulation and implantation in the cynomolgus macaque (Macaca fascicularis) through evaluations of urinary estrone conjugates and progesterone metabolites: a technique for the routine evaluation of reproductive parameters.

Investigations were undertaken to determine the applicability of recently reported specific radioimmunoassays for urinary estrone conjugates and progesterone metabolites for monitoring ovarian function in the cynomolgus macaque (Macaca fasciularis) and other macaque species. Mean estrone conjugate measurements appear to accurately reflect the preovulatory estrogen peak in both conceptive (n = 5) and nonconceptive (n = 6) cycles, as well as to indicate early pregnancy through increases which are significantly elevated by Day + 15 (p less than 0.049) post estrone conjugates peak. The mean luteal phase levels of these progesterone metabolites are significantly elevated by Day + 14 (p less than 0.012) in conceptive cycles when compared to the mean values for nonconceptive cycles.

Animals↗