Using estrus detection patches to optimally time insemination improved pregnancy risk in suckled beef cows enrolled in a fixed-time artificial insemination program.

A multilocation study examined pregnancy risk (PR) after delaying AI in suckled beef cows from 60 to 75 h when estrus had not been detected by 60 h in response to a 7-d CO-Synch + progesterone insert (CIDR) timed AI (TAI) program (d -7: CIDR insert concurrent with an injection of GnRH; d 0: PGF injection and removal of CIDR insert; and GnRH injection at TAI [60 or 75 h after CIDR removal]). A total of 1,611 suckled beef cows at 15 locations in 9 states (CO, IL, KS, MN, MS, MT, ND, SD, and VA) were enrolled. Before applying the fixed-time AI program, BCS was assessed, and blood samples were collected. Estrus was defined to have occurred when an estrus detection patch was >50% colored (activated). Pregnancy was determined 35 d after AI via transrectal ultrasound. Cows ( = 746) detected in estrus by 60 h (46.3%) after CIDR removal were inseminated and treated with GnRH at AI (Control). Remaining nonestrous cows were allocated within location to 3 treatments on the basis of parity and days postpartum: 1) GnRH injection and AI at 60 h (early-early = EE; = 292), 2) GnRH injection at 60 h and AI at 75 h (early-delayed = ED; = 282), or 3) GnRH injection and AI at 75 h (delayed-delayed = DD; = 291). Control cows had a greater ( < 0.01) PR (64.2%) than other treatments (EE = 41.7%, ED = 52.8%, DD = 50.0%). Use of estrus detection patches to delay AI in cows not in estrus by 60 h after CIDR insert removal (ED and DD treatments) increased ( < 0.05) PR to TAI when compared with cows in the EE treatment. More ( < 0.001) cows that showed estrus by 60 h conceived to AI at 60 h than those not showing estrus (64.2% vs. 48.1%). Approximately half (49.2%) of the cows not in estrus by 60 h had activated patches by 75 h, resulting in a greater ( < 0.05) PR than their nonestrous herd mates in the EE (46.1% vs. 34.5%), ED (64.2% vs. 39.2%), and DD (64.8% vs. 31.5%) treatments, respectively. Overall, cows showing estrus by 75 h (72.7%) had greater ( < 0.001) PR to AI (61.3% vs. 37.9%) than cows not showing estrus. Use of estrus detection patches to allow for a delayed AI in cows not in estrus by 60 h after removal of the CIDR insert improved PR to TAI by optimizing the timing of the AI in those cows.

Effects of administration of prostaglandin F at initiation of the seven-day CO-Synch+controlled internal drug release ovulation synchronization protocol for suckled beef cows and replacement beef heifers.

Two experiments were conducted to determine the effect of administering PGF at the initiation of the 7-d CO-Synch+controlled internal drug release (CIDR) fixed-timed AI (TAI) protocol on pregnancy rates of suckled beef cows and replacement heifers. Within location, cows were stratified by days postpartum (DPP), BCS, and parity (Exp. 1; = 1,551) and heifers were stratified by BCS (Exp. 2; = 999) and randomly assigned to 1 of 2 treatments: 1) CO-Synch+CIDR (100-µg injection of GnRH at CIDR insertion [d -10] with a 25-mg injection of PGF at CIDR removal [d -3] followed by injection of GnRH and TAI on d 0) or 2) PG-CO-Synch+CIDR (a 25-mg injection of PGF on d -10 of the CO-Synch+CIDR protocol). Follicle diameter and corpus luteum (CL) development were assessed on d -10 and -3, and pregnancy status was determined on d 30 to 35. Blood was collected on d -20, -10, -3, and 0 relative to TAI to determine concentrations of progesterone (P4). In Exp. 1, TAI pregnancy rates did not differ ( = 0.667) between treatments and were affected by BCS ( = 0.003) and DPP ( = 0.006). Concentrations of P4 were greater ( < 0.0001) on d -3 for CO-Synch+CIDR than for PG-CO-Synch+CIDR (4.1 ± 0.2 and 3.4 ± 0.2 ng/mL, respectively). Follicle diameter on d -3 differed ( = 0.05) between PG-CO-Synch+CIDR (13.4 ± 0.3 mm) and CO-Synch+CIDR (12.5 ± 0.3 mm) treatments. Cows with P4 > 2.5 ng/mL on d -10 had greater ( = 0.024) pregnancy rate to TAI (56.5%) compared with cows with 2.5 ng/mL < P4 > 1 (43.0%), whereas cows with P4 < 1 ng/mL were intermediate (51.6%). Cows with a CL on d -10 had greater ( = 0.012) pregnancy rates to TAI than cows without a CL (66.3 vs. 39.4%, respectively). In Exp. 2, TAI pregnancy rates did not differ ( = 0.316) between treatments. Concentrations of P4 differed ( < 0.0001) on d -3 with greater concentrations of P4 for CO-Synch+CIDR than for PG-CO-Synch+CIDR (3.75 ± 0.20 ng/mL and 3.60 ± 0.21 ng/mL, respectively). Follicle diameter was similar ( = 0.749) between treatments on d -10 and -3. Regardless of treatment, cyclic status tended ( = 0.062) to improve pregnancy rates to TAI (55 vs. 45%, for cycling and noncycling heifers, respectively). We concluded that addition of PGF to the 7-d CO-Synch+CIDR protocol decreased concentrations of P4 in cows and heifers and increased follicle diameter at CIDR removal in cows but failed to increase TAI pregnancy rates.

Developmental programing: impact of testosterone on placental differentiation.

Gestational testosterone treatment causes maternal hyperinsulinemia, intrauterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. Sheep models of IUGR demonstrate placental insufficiency as an underlying cause of IUGR. Placental compromise is probably the cause of fetal growth retardation in gestational testosterone-treated sheep. This study tested whether testosterone excess compromises placental differentiation by its androgenic action and/or via altered insulin sensitivity. A comparative approach of studying gestational testosterone (aromatizable androgen) against dihydrotestosterone (non-aromatizable androgen) or testosterone plus androgen antagonist, flutamide, was used to determine whether the effects of testosterone on placental differentiation were programed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational testosterone on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that i) gestational testosterone treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, ii) placental advancement is facilitated at least in part by androgenic actions of testosterone and is not a function of disrupted insulin homeostasis, and iii) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low-birth-weight female offspring. Findings from this study may be of relevance to women with polycystic ovary syndrome, whose reproductive and metabolic phenotype is captured by the gestational testosterone-treated offspring.

Developmental programming: postnatal estradiol amplifies ovarian follicular defects induced by fetal exposure to excess testosterone and dihydrotestosterone in sheep.

Excess of prenatal testosterone (T) induces reproductive defects including follicular persistence. Comparative studies with T and dihydrotestosterone (DHT) have suggested that follicular persistence is programmed via estrogenic actions of T. This study addresses the androgenic and estrogenic contributions in programming follicular persistence. Because humans are exposed to estrogenic environmental steroids from various sources throughout their life span and postnatal insults may also induce organizational and/or activational changes, we tested whether continuous postnatal exposure to estradiol (E) will amplify effects of prenatal steroids on ovarian function. Pregnant sheep were treated with T, DHT, E, or ED (E and DHT) from days 30 to 90 of gestation. Postnatally, a subset of the vehicle (C), T, and DHT females received an E implant. Transrectal ultrasonography was performed in the first breeding season during a synchronized cycle to monitor ovarian follicular dynamics. As expected, number of ≥8 mm follicles was higher in the T versus C group. Postnatal E reduced the number of 4 to 8 mm follicles in the DHT group. Percentage of females bearing luteinized follicles and the number of luteinized follicles differed among prenatal groups. Postnatal E increased the incidence of subluteal cycles in the prenatal T-treated females. Findings from this study confirm previous findings of divergences in programming effects of prenatal androgens and estrogens. They also indicate that some aspects of follicular dynamics are subject to postnatal modulation as well as support the existence of an extended organizational period or the need for a second insult to uncover the previously programmed event.

Developmental reprogramming of reproductive and metabolic dysfunction in sheep: native steroids vs. environmental steroid receptor modulators.

The inappropriate programming of developing organ systems by exposure to excess native or environmental steroids, particularly the contamination of our environment and our food sources with synthetic endocrine disrupting chemicals that can interact with steroid receptors, is a major concern. Studies with native steroids have found that in utero exposure of sheep to excess testosterone, an oestrogen precursor, results in low birth weight offspring and leads to an array of adult reproductive/metabolic deficits manifested as cycle defects, functional hyperandrogenism, neuroendocrine/ovarian defects, insulin resistance and hypertension. Furthermore, the severity of reproductive dysfunction is amplified by excess postnatal weight gain. The constellation of adult reproductive and metabolic dysfunction in prenatal testosterone-treated sheep is similar to features seen in women with polycystic ovary syndrome. Prenatal dihydrotestosterone treatment failed to result in similar phenotype suggesting that many effects of prenatal testosterone excess are likely facilitated via aromatization to oestradiol. Similarly, exposure to environmental steroid imposters such as bisphenol A (BPA) and methoxychlor (MXC) from days 30 to 90 of gestation had long-term but differential effects. Exposure of sheep to BPA, which resulted in maternal levels of 30-50 ng/mL BPA, culminated in low birth weight offspring. These female offspring were hypergonadotropic during early postnatal life and characterized by severely dampened preovulatory LH surges. Prenatal MXC-treated females had normal birth weight and manifested delayed but normal amplitude LH surges. Importantly, the effects of BPA were evident at levels, which approximated twice the highest levels found in human maternal circulation of industrialized nations. These findings provide evidence in support of developmental origin of adult reproductive and metabolic diseases and highlight the risk posed by exposure to environmental endocrine disrupting chemicals.

Developmental programming in sheep: administration of testosterone during 60-90 days of pregnancy reduces breeding success and pregnancy outcome.

Evidence suggests that exposure to excess steroids during critical periods of fetal development leads to reproductive disorders. Exposure of female lambs to excess testosterone (T) from Days 60 to 90 of gestation (T60-90; term, 147 days) delayed onset of the LH surge and resulted in to male-typical reproductive behavior. The objectives of this study were to test the ability of T60-90 ewes to mate, conceive and lamb during the first three breeding seasons (Years 1, 2 and 3). Pregnant Suffolk ewes were injected with T propionate in cottonseed oil (100mg, im twice weekly) or vehicle (control; C) from Days 60 to 90 of gestation. In Year 1, ewes (C=12, T60-90=12) were kept with a vasectomized ram for 3 months and markings/visual observation of copulations were recorded. Rams had paint applied to their chest to facilitate detection of estrus and mating. All C but only three T60-90 ewes were marked (P<0.001). All ewes were then estrus-synchronized with two injections of prostaglandin F2alpha (20mg, im) given 11 days apart and allowed to mate with a painted, fertile ram. Nine of 12 C and 4 of 12 T60-90 ewes (P=0.1) were mated. Based on estrus and long-term monitoring of progesterone, more C than T60-90 became pregnant (82 and 18%, respectively; P<0.01). In Year 2, to maximize ram exposure, two C and two T60-90 estrus-synchronized ewes were placed with a painted, fertile ram at a time and mated ewes were removed to a nearby pen to force mating with others. Twenty-four hour video monitoring revealed the rams mated more C than T60-90 ewes (83 and 25%, respectively; P=0.01). In both Years 1 and 2, the rams preferred C over T60-90 ewes; therefore in Year 3 rams were given access only to T60-90 ewes. Only four T60-90 estrus-synchronized ewes were placed with a painted ram at a time. Not given an option, 91% of the T60-90 ewes were marked resulting in 4 of 11 (36%; first-service pregnancy rate in the breeding herd was 91%) ewes becoming pregnant to the synchronized estrus. Collectively these studies showed that fertility in T60-90 females was severely compromised, even after overcoming ram preference for controls.

Gonadorelin-induced testosterone release: a biological assay for quality assurance of gonadorelin in veterinary medicine.

Two experiments were conducted with bulls administered norgestomet and gonadorelin to determine if the gonadorelin-induced release of testosterone could be developed into a biological assay for quality assurance of gonadorelin. Implants containing norgestomet (0 to 36 mg) reduced the episodic release (r = -.81; P < .05) and mean concentrations of testosterone (r = -.82; P < .05). Gonadoreline-induced testosterone release increased (r = .99; P < .05) with increasing dosage of gonadorelin (up to 5 micrograms) in norgestomet-implanted bulls (36 mg). Maximal testosterone was released (> sixfold increase) with 5 to 40 micrograms of gonadorelin. In summary, the gonadorelin-induced testosterone release in bulls administered a synthetic progestin is a sensitive (0.008 microgram per kg body weight for 5 micrograms of gonadorelin) biological assay with a rapid turnaround time for the confirmation of gonadorelin potency. Based on a per-kg-body-weight basis, the norgestomet-treated bull is the most sensitive biological assay model.

Effect of prostaglandin F2 alpha treatment before norgestomet and estradiol valerate treatment on regression, formation, and function of corpora lutea in beef heifers.

Two experiments were conducted to determine if corpus luteum regression, formation, and function were associated with the decreased calving rate observed in beef females administered PGF2 alpha 5 days before Syncro-Mate B (SMB) treatment. Experiment 1 included 31 beef heifers 11 to 13 months old and experiment 2 included 31 beef heifers 19 to 21 months old. Heifers were randomly assigned to 1 of 2 groups (control and PGF2 alpha 5 days before SMB treatment). Heifers were bled 10 days before PGF2 alpha treatment, immediately before PGF2 alpha and SMB treatments, at the time of implant removal, and twice weekly after implant removal. Heifers in experiment 2 were observed twice daily for estrus for 5 days after PGF2 alpha treatment and for 3 days after norgestomet implant removal. Based on the blood samples collected before SMB treatment, 15 heifers in experiment 1 and every heifer in experiment 2 were with estrous cycles. All heifers in experiment 1 had progesterone concentrations < 0.5 ng/ml 2 days after implant removal. However, progesterone concentrations during the luteal phase in control heifers with estrous cycles were higher (P < 0.05) than in PGF2 alpha treated heifers with estrous cycles and in heifers previously without estrous cycles. In experiment 2, based on the occurrence of estrus and progesterone concentrations, heifers were also classified as metestrus or diestrus at the time of SMB treatment. The data were analyzed as a 2 x 2 factorial with treatment (control or PGF2 alpha) and stage of the cycle (metestrus and diestrus) as main effects. More metestrus heifers (40%) had progesterone concentrations > 1.0 ng/ml 2 days after implant removal than diestrus heifers (0%). In addition, progesterone concentrations during the luteal phase in metestrus heifers were lower (P < 0.05) than in diestrus heifers. PGF2 alpha treatment had no effect (P > 0.25) on the number of heifers with > 1.0 ng/ml progesterone 2 days after implant removal and progesterone concentrations during the luteal phase. There was no treatment by stage of the estrous cycle interactions. In summary, the administration of PGF2 alpha 5 days before SMB decreased the calving rate by causing more heifers to be metestrus at SMB treatment. Fewer metestrus heifers (than diestrus heifers) were synchronized (with < 1.0 ng/ml of progesterone 2 days after implant removal) to SMB treatment and those synchronized had lower progesterone concentrations during the luteal phase.

Central pontine myelinolysis in a patient with bulimia.

Central pontine myelinolysis is classically described in alcoholics or other malnourished individuals after correction of severe hyponatremia. A patient with bulimia developed central pontine myelinolysis after correction of severe hyponatremia and hypokalemia. Early symptoms of abnormal affect and dystonia made initial diagnosis elusive. The spectrum of neurologic signs and possible causes of central pontine myelinolysis are discussed. A conservative approach to treatment of hyponatremia is advocated.

Lithium- and carbamazepine-associated sinus node dysfunction: nine-year experience in a psychiatric hospital.

The cardiac effects of lithium and carbamazepine are considered rare, but both are known to induce sinus node dysfunction. The author presents the 9-year experience in a state mental hospital with lithium-induced sinus node dysfunction. Four of the five patients were also on carbamazepine. The clinical features of previously reported cases of lithium- and carbamazepine-associated sinus node dysfunction are reviewed. A role for carbamazepine in lithium-induced sinus node dysfunction is discussed.

Grades 1 and 2 hypothyroidism in a state mental hospital: risk factors and clinical findings.

Thirty-six chronically psychotic patients (nine men and 27 women, mean age 56.7 +/- S.D. 13.4 years) were found to have elevated thyroid stimulating hormone (TSH) levels during review of thyroid function screening tests of 1150 patients over a 15 month period in a 700 bed state mental hospital. This study population of 36 patients was more likely to be female and older than the general hospital population. The spectrum and frequency of psychiatric diagnoses included dementia (3); schizoaffective disorder (12); bipolar disorder (6); schizophrenic disorder (4); organic affective disorder (7); major depression (3); and mental retardation (1). Only nine of these 36 patients failed to receive the goitrogens lithium (LI), carbamazepine (CBZ) and/or phenytoin (PTN) and five of those nine patients had a history of thyroid disease. Sex did not predict age, thyroxine (T4) level, triiodothyronine (T3) uptake, or TSH. The distribution of psychiatric diagnoses were the same for both sexes. Expectedly, there was an inverse relationship between TSH and T4 and T3 uptake. Using T4 to separate grades 1 and 2 hypothyroidism revealed that six (17%) patients had grade 1 disease. Men were more likely to have a seizure disorder and receive LI, CBZ, and PTN. Women were more likely to have a history of thyroid disease. The goitrogenic effects of LI + CBZ seemed additive compared with patients receiving LI alone. While T4, T3 uptake, and LI levels were the same for the two groups, patients receiving LI + CBZ had higher TSH values (p = 0.028) than did patients receiving LI alone.(ABSTRACT TRUNCATED AT 250 WORDS)