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Estradiol-17β (E2) increases kallikrein in rodent and human reproductive tissues. Kallikrein specific activity is increased in the porcine uterus when conceptus E2 is secreted at maternal recognition of pregnancy. When kallikrein acts on kininogen to liberate bradykinin, angiogenic and vasoactive factors are released. The uterus of ovariectomized ewes administered E2 undergoes rapid vascular changes via different patterns of angiogenic and vasoactive factors. Our hypothesis was that E2 would increase the specific activity and protein secretion of tissue kallikrein in endometrial explants culture media (ECM) and ewes exposed to E2 would have uterine arteries that would be more sensitive to the vasodilatory effects of bradykinin. Ovariectomized ewes received 100 mg of E2 implants for 0, 12, 24, or 48 h. After treatment, uterine weights were determined, and caruncles were processed for ECM. Uterine weights and uterine weight per ewe body weight were significantly greater in the 12 and 24 h ewes compared with the 0 h ewes, with the 48 h ewes being similar to the 24 h ewes. There were no statistically significant differences in caruncular tissue kallikrein protein secretion among the treatment groups. There was a tendency (P = 0.09) for duration of E2 exposure to influence tissue kallikrein specific activity where kallikrein activity was greater (P ≤ 0.05) in the 12 and 48 h ewes compared with the 0 h ewes, with 24 h ewes being intermediate (unprotected F test). Uterine arteries from ewes with E2 for 24 and 48 h had more sensitivity to bradykinin, via the bradykinin receptor 2, than uterine arteries from ewes with 0 or 12 h E2 exposure. We fail to reject our hypothesis as E2 did elicit a positive response in tissue kallikrein specific activity and bradykinin response. Further investigations are needed to determine how kallikrein and bradykinin may be involved in vascular remodeling of the ovine uterus.

The objective of the current study was to determine the effects of maternal MP restriction or supplementation during late gestation on male offspring feedlot performance, carcass characteristics, and nitrogen retention. In yr 1, maternal dietary treatments were applied at d 100 of gestation, were similar in total energy, and contained: 60MP1: 60% of MP requirements; 80MP1: 80% of MP requirements; and 100MP1: 100% of the MP requirements on a DM basis during late gestation. In yr 2, maternal dietary treatments were similar in total energy and contained: 60MP2: 60% of MP requirements; 100MP2: 100% of the MP requirements; and 140MP2: 140% of MP requirements on a DM basis during late gestation. In yr 1, there was no effect (P ≥ 0.14) of maternal dietary treatment on initial BW, final BW, ADG, G:F, or morbidity. There was a quadratic effect (P = 0.04) for days on feed, with the 80MP1 lambs being on feed longer than the 60MP1 and 100MP1 lambs. A quadratic effect (P = 0.05) was also observed for DMI, with the 80MP1 wethers consuming less feed than the 60MP1 and 100MP1 wethers. There was no effect (P ≥ 0.06) of maternal MP intake during late gestation on the carcass characteristics or the majority of N balance parameters of initial BW, DM, NDF, ADF, or N digestibility, daily fecal N excretion, or daily N balance of wethers in yr 1. However, daily urinary N excretion per unit of initial BW was linearly reduced (P = 0.02) as MP intake increased and daily digested N retained increased linearly (P = 0.04) as maternal MP increased. There was a treatment × day interaction (P = 0.004) for serum urea N concentrations. The 60MP1 wethers had greater serum urea N concentrations on d 16, 18, 19, and 20 (P ≤ 0.04) than 80MP1 and 100MP1 wethers; and on d 17 (P = 0.05) compared with 80MP1 wethers. In yr 2, there was no effect (P ≥ 0.18) of maternal dietary treatment on initial BW, final BW, ADG, G:F, or morbidity. There was a linear increase (P = 0.04) in DMI as maternal MP increased from 60 to 140% of MP requirements. Carcass characteristics (P ≥ 0.29) and N balance parameters (P ≥ 0.24) in yr 2 were not affected by ewe MP intake during late gestation. These results suggest that maternal MP intake above or below requirements during late gestation may not affect wether feedlot performance or carcass characteristics.

Objectives were to determine the effects of advancing gestation, maternal nutrient restriction during early and mid-gestation, and realimentation on fetal liver and jejunal mass and energy use in both dams and fetuses. On day 30 of pregnancy, multiparous, non-lactating beef cows (initial BW=621±11.3 kg and body condition score=5.1±0.1) were assigned to one of the two dietary treatments: control (CON; 100% requirements; n=18) and restricted (R; 60% requirements; n=28). On day 85, cows were slaughtered (CON, n=6; R, n=6), and remaining cows continued on control (CC; n=12) and restricted (RR; n=12) diets, or were realimented to the control diet (RC; n=11). On day 140, cows were slaughtered (CC, n=6; RR, n=6; RC, n=5), remaining cows continued on the control diet (CCC, n=6; RCC, n=5), or were realimented to the control diet (RRC, n=6). On day 254, all remaining cows were slaughtered. Maternal liver O2 consumption linearly increased (P⩽0.04) and jejunal weight (g/kg) linearly decreased (P=0.04) as gestation advanced in CON groups. Fetal BW, and hepatic and small intestinal absolute mass, protein content and O2 consumption linearly increased (P⩽0.04) as pregnancy advanced in CON groups. However, mass and O2 consumption relative to BW linearly decreased (P⩽0.001) in the fetal liver in CON groups. When analyzing the effects of dietary treatment, at day 85, fetal jejunal O2 consumption (mol/min per kg BW) was lower (P=0.02) in the R group when compared with the CON group. At day 140, maternal hepatic weight (g) was lower (P=0.02) in RC and RR cows when compared with CC, and fetal jejunual O2 consumption (mmol/min per mg tissue and mmol/min per g protein) was greater (P⩽0.02) in RC when compared with RR. At day 254, maternal hepatic O2 consumption (absolute and relative to BW) was lower (P⩽0.04) in the RCC cows when compared with RRC. Fetal hepatic weight was lower (P=0.05) in the CCC group when compared with RCC and RRC. The changes in response to nutrient restriction and realimentation in both the dam and fetus may indicate an adaptation to a lower amount of available nutrients by altering tissue mass and metabolism.

Primiparous ewes (n=32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P⩽0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 µm2) and giant (⩾512 001 µm2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P⩽0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm2) while fetuses had more (P

The objective was to examine hepatic steroid inactivating enzymes throughout gestation and determine the effect of early to mid-gestation maternal nutrient restriction followed by realimentation on the activity of these enzymes. On day 30 of gestation, cows were assigned to dietary treatments: control (CON; 100% National Research Council; n = 18) and restricted (RES; 60% National Research Council; n = 30). On day 85, cows were slaughtered (CON, n = 6 and RES, n = 6), remained on control (CC, n = 12) and restricted (RR, n = 12), or were realimented to control (RC, n = 11). On day 140, cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5), or were realimented to control (RRC, n = 6). On day 254, all remaining cows were slaughtered. Jugular blood samples were collected before the slaughter for steroid analysis. At slaughter, maternal liver samples were collected for hepatic enzyme activity analysis. Activity of cytochrome P450 3A decreased (P = 0.05) from mid- to late-gestation. Peroxisome proliferator-activated receptor alpha DNA binding activity was increased (P0.01) on day 140 and 254 of gestation vs day 85. Concentrations of estradiol-17β (E2) increased (P0.01) as gestation proceeded, whereas progesterone concentrations (P4) tended to increase (P = 0.06) from mid- to late-gestation. Activity of cytochrome P450 1A and 2C were decreased (P0.05) in nutrient restricted cows vs control, whereas concentrations of E2 were increased (P0.05) in nutrient restricted cows vs control. A longer period of nutrient realimentation from mid- to late-gestation increased (P0.05) aldo-keto reductase 1C activity and decreased (P0.05) P4 concentrations compared with the shorter period of nutrient realimentation. In addition, significant negative correlations were observed for cytochrome P450 3A activity vs E2 (r(2) = -0.30; P0.05) and aldo-keto reductase 1C activity vs P4 (r(2) = -0.29; P0.05). The present study implicates hepatic steroid inactivation in the partial modulation of peripheral concentrations of E2 and P4 during gestation.

Maternal nutrient restriction and decreased scotophase concentrations of melatonin have been associated with severely compromised pregnancies. We hypothesized that melatonin supplementation in a compromised pregnancy enhances the bradykinin (BK)-induced relaxations of placental arteries thereby ensuring sufficient umbilical blood flow to the developing fetus.Pregnant ewes (n = 31) were fed an adequate (ADQ) or nutrient restricted (RES) diet supplemented with 5 mg of melatonin (MEL) or without melatonin (CON) from day 50 to 130 of gestation. On day 130 of gestation, the maternal (caruncular; CAR) and fetal (cotyledonary; COT) placental arteries were suspended in organ chambers for isometric tension recording.There were no treatment or dietary effects on CAR arteries for any vasoactive agent. However, in COT arteries, MEL ewes were more sensitive (P 0.01) to bradykinin-induced relaxation than CON ewes. There was a melatonin by nutritional level interaction (P 0.01) with sodium nitroprusside-induced relaxation of COT arteries where CON-RES were more sensitive to sodium nitroprusside compared to CON-ADQ, which was in contrast to when ewes were fed MEL. There was a significant melatonin by nutritional interaction (P = 0.04) for responsiveness to norepinephrine. The sensitivity of the COT arteries to norepinephrine in CON-RES ewes was decreased compared to CON-ADQ. Melatonin supplementation, regardless of maternal dietary intake, resulted in COT arteries having similar responsiveness to CON-RES ewes.An increase in placental vessel sensitivity to bradykinin-induced relaxation may contribute to melatonin-induced increases in umbilical artery blood flow.

Objectives were to examine effects of selenium (Se) supply and maternal nutritional plane during gestation on placental size at term and maternal endocrine profiles throughout gestation and early lactation. Ewe lambs (n = 84) were allocated to treatments that included Se supply of adequate Se (ASe; 11.5 μg/kg BW) or high Se (HSe; 77 μg/kg BW) initiated at breeding and nutritional plane of 60% (RES), 100% (CON), or 140% (EXC) of requirements beginning on day 40 of gestation. At parturition, lambs were removed from their dams, and ewes were transitioned to a common diet that met requirements of lactation. Blood samples were taken from a subset of ewes (n = 42) throughout gestation, during parturition, and throughout lactation to determine hormone concentrations. Cotyledon number was reduced (P = 0.03) in RES and EXC ewes compared with CON ewes. Placental delivery time tended (P = 0.08) to be shorter in HSe ewes than in ASe ewes, whereas placental delivery time was longer (P = 0.02) in RES ewes than in CON and EXC ewes. During gestation, maternal progesterone, estradiol-17β, and GH were increased (P < 0.05) in RES ewes and decreased (P < 0.05) in EXC ewes compared with CON ewes. In contrast, maternal cortisol, IGF-I, prolactin, triiodothyronine, and thyroxine were decreased in RES ewes and increased in EXC ewes compared with CON ewes during gestation. Selenium supply did not alter maternal hormone profiles during gestation. During parturition and lactation, maternal hormone concentrations were influenced by both Se and maternal nutritional plane. During the parturient process, HSe ewes tended to have greater (P = 0.06) concentrations of estradiol-17β than ASe ewes. Three hours after parturition a surge of GH was observed in ASe-RES ewes that was muted in HSe-RES ewes and not apparent in other ewes. Growth hormone area under the curve during the parturient process was increased (P < 0.05) in ASe-RES vs HSe-RES ewes. Ewes that were overfed during gestation had reduced (P < 0.05) estradiol-17β but greater IGF-I, triiodothyronine, and thyroxine (P < 0.05) compared with RES ewes. Even though ewes were transitioned to a common diet after parturition, endocrine status continued to be affected into lactation. Moreover, it appears that gestational diet may partially affect lactational performance through altered endocrine status.

To determine the impacts of Se supply and maternal dietary intake on ewe organ mass and endocrine and metabolic changes throughout gestation, pregnant first parity ewes (n=77) were allocated to 6 treatments in a 2×3 factorial array. Factors included Se [adequate Se (ASe; 9.5μg/kg BW) vs. high Se (HSe; 81.8μg/kg BW)] initiated at breeding and dietary intake [60% (RES), 100% (CON), or 140% (EXC) of requirements] initiated on d 50 of gestation. Ewes were individually fed and blood samples from the jugular vein were obtained approximately every 14 d from d 50 until parturition. Maternal Se supply did not impact endocrine or metabolic status. There was a nutritional intake by day interaction for NEFA, blood urea nitrogen (BUN), insulin, triiodothyronine (T3), thyroxine (T4), progesterone (P4), and estradiol-17β (E2). As expected, with increased maternal intake, NEFA concentrations were reduced. During the last weeks of gestation, BUN and insulin were elevated in EXC compared with RES ewes. Although the pattern of T3 and T4 differed throughout gestation within a treatment group, as maternal intake increased, circulating T3 and T4 were increased. For P4 and E2, as maternal dietary intake increased, there was a reduction in the steroid concentrations in jugular blood. There was only a main effect of maternal nutrition (P

To examine effects of maternal nutrition and Se intake on adiposity and insulin sensitivity in female offspring, treatments were imposed during gestation on 82 pregnant primiparous Rambouillet ewe lambs (52.2 ± 0.8 kg) allotted randomly to 1 of 6 treatments in a 2 × 3 factorial arrangement. Factors were adequate (9.5 μg Se·kg BW(-1)·d(-1); ASe) or high (81.8 μg Se·kg BW(-1)·d(-1); HSe) levels of dietary Se (Se-enriched yeast) and maternal nutritional intake (100% of metabolizable energy [ME] requirement [MOD], 60% of MOD [LOW], and 140% of MOD [HIGH]). Selenium treatments were initiated at breeding and global nutritional treatments at day 50 of gestation. At parturition, lambs were removed from ewes before nursing and managed similarly. Glucose tolerance tests were performed at 107 and 148 d of age. Necropsies were performed at 180 d of age. Although there was no effect of Se on maternal body condition or weight during gestation, both maternal nutritional intake and selenium treatment influenced (P ≤ 0.04) offspring growth and response to a glucose tolerance test. Female lambs from HSe ewes were heavier (P = 0.04) at birth. There were nutritional intake and Se interactions (P ≤ 0.05) on the growth rate of the lambs and their insulin response to a glucose bolus at 2 different times during growth. By 180 d, ewe lambs from HSe ewes had more (P ≤ 0.07) internal fat stores than lambs from ASe ewes. It appears that both maternal nutritional level and Se intake can influence insulin sensitivity, and maternal Se intake alone can enhance fat deposition in female offspring.

To examine the effects of maternal supranutritional selenium (Se) and nutrient restriction during mid and late gestation on placental characteristics and fetal liver glycogen, ewes received either adequate Se (ASe) or high Se (HSe) prior to breeding. On d 64 of gestation, ASe and HSe ewes remained at 100% of requirements (controls; CON) or were restricted (RES; 60% of requirements). On d 135 of gestation, fetal weight (P ≤ 0.08) was greatest in both HSe and CON ewes. Placentome number, mass, and caruncular and cotyledonary weight were not different (P ≥ 0.17) among treatments. Fetal mass:placental mass ratio was less (P = 0.06) in RES compared to CON ewes. Compared to ASe, HSe exhibited increased (P ≤ 0.08) cellular proliferation and DNA concentration and decreased (P = 0.07) cellular size in cotyledonary tissue. Nutritional restriction decreased (P ≤ 0.08) cotyledonary protein concentration and cellular size. VEGF receptor 1 (Flt) mRNA in cotyledonary tissue was greater in HSe compared with ASe ewes (P = 0.06) and in RES compared with CON ewes (P = 0.08). There was no effect of diet on caruncular growth variables (P ≥ 0.13) or on placental vascularity (P ≥ 0.11). Progesterone was greater (P ≤ 0.08) in ASe–RES ewes compared to all groups at d 90 and ASe–CON and HSe–CON at d 104. Although fetal glucose and cortisol concentrations were not affected by diet, fetal liver glycogen was greater (P = 0.04) in ASe–RES compared to ASe–CON and HSe–RES ewes with HSe–CON being intermediate. Both Se and nutritional plane may impact placental function and fetal growth, as fetal weight and liver glycogen are altered despite similar placental vascularity measurements.

To evaluate the estrogenic potential of secoisolariciresinol diglycoside (SDG) found in linseed meal (LSM) on visceral organ mass, IGF-I, and thyroid hormone (T(3) and T(4)) concentrations, 48 multiparous, ovariectomized ewes (54.6 +/- 1.1 kg) were used in a 3 x 4 factorial arrangement. Main effects were length of LSM feeding (0, 1, 7, or 14 d) and length of exposure to estradiol-17beta (E(2)) implant (0, 6, or 24 h prior to tissue collection). Implanting ewes with E(2) for 24h increased liver mass relative to empty body weight (EBW; g/kg EBW) compared with ewes implanted for 0 or 6 h (Por= 0.03), whereas feeding LSM for 14 d decreased liver mass compared with ewes fed LSM for 1 or 7 d (Por= 0.02). There was an LSM x E(2) interaction (P = 0.01) for duodenal mass (g/kg EBW), LSM, and E(2) tended (P = 0.07) to influence the stomach complex mass; however, ileal mass was not affected. Neither LSM nor E(2) affected (Por= 0.12) CYP2C or CYP3A mRNA expression or cellularity of the liver. Exogenous E(2) influenced circulating concentrations of IGF-I, T(3), and T(4). The estrogenic or anti-estrogenic potential of LSM is dependent upon the tissue, exposure to E(2), and the duration of LSM feeding. Feeding LSM during gestation, lactation, or during the grow-finish phase warrants further investigation.

To examine the effects of maternal metabolizable protein (MP) supplementation during late gestation on serum hormone and metabolites and organ masses, multiparous ewes (n = 45) carrying singletons or twins were allotted randomly (within pregnancy group) to 1 of 3 treatments: 60% (MP60), 80% (MP80), or 100% (MP100) of MP requirements. Blood samples were drawn before the initiation of diets (day 100) and before slaughter (day 130) for chemistry panel analysis and weekly for hormone analysis including progesterone (P4) and estradiol-17β (E2). At day 130, ewe organ masses were recorded. Despite being fed isocaloric diets, MP60 ewes gained less weight throughout pregnancy compared with MP80 and MP100 ewes which were similar. Although diet did not impact E2 or P4 concentrations, ewes carrying twins had greater (P < 0.05) concentrations of both as gestation advanced. Albumin, aspartate aminotransferase, and total protein were reduced (P < 0.05) in MP60 compared with MP100 ewes near term. There was a diet by fetal number interaction (P = 0.03) for lactate dehydrogenase. Twin-carrying MP80 ewes had greater lactate dehydrogenase compared with all other groups on day 130 of gestation. Ewes that were fed MP80 had greater body weight on day 130 of gestation compared with MP60 ewes. Kidney and heart weights were lighter in MP60 ewes compared with MP80 ewes. There was a maternal diet by fetal number interaction (P = 0.05) on fetal weight per unit empty ewe body weight. In ewes carrying singletons, MP60 ewes supported less fetal weight compared with MP100. In contrast, MP60 ewes supported more fetal mass compared with MP100 ewes when carrying twins. The level of protein, and not just total energy, in the diet appears to impact some aspects of the maternal system. Moreover, it appears some measurements of mobilizing maternal body resources are enhanced in ewes carrying twins.

The objective was to examine the effect of maternal nutrient restriction followed by realimentation during midgestation on uterine blood flow (BF). On Day 30 of pregnancy, lactating, multiparous Simmental beef cows were assigned randomly to treatments: control (CON; 100% National Research Council; n = 6) and nutrient restriction (RES; 60% of CON; n = 4) from Day 30 to 140 (period 1), and thereafter, realimented to CON until Day 198 of gestation (period 2). Uterine BF, pulsatility index (PI), and resistance index (RI) were obtained from both the ipsilateral and contralateral uterine arteries via Doppler ultrasonography. Generalized least square analysis was performed. Ipsilateral uterine BF in both groups increased quadratically (P < 0.01) during period 1 and linearly (P < 0.01) during period 2. There was a treatment (P = 0.05) effect during period 2; where RES cows had greater ipsilateral BF versus CON. Ipsilateral uterine PI and RI decreased linearly (P ≤ 0.01) during period 1 across treatments. Contralateral uterine BF in CON cows tended (P < 0.09) to be greater versus RES in both periods. Contralateral PI in both groups increased linearly (P ≤ 0.01) during period 1. Contralateral uterine RI was increased (P ≤ 0.05) in RES cows versus CON in both periods. There was no interaction or treatment effect (P ≥ 0.24) for total BF during either period. Nutrient restriction does not alter total uterine BF, but it may increase vascular resistance. However, up on realimentation, local conceptus-derived vasoactive factors appear to influence ipsilateral uterine BF.