The onset of lactation requires a variety of physiological adaptions as a mammal transitions from a non-lactating to lactating state. In order to initiate lactation, a coordination of changes in tissue metabolism occurs in response to the physiological demands of lactation. Due to these immense nutrient demands by the mammary gland, many maternal adaptations occur to support lactation (Bauman & Currie, 1980). To meet these demands, in addition to traditionally

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants used by pregnant women. However, adverse pregnancy outcomes have been described in women taking SSRI during pregnancy—placental lesions, premature birth, poor neonatal adaptation. We aimed to investigate the effects of fluoxetine (Prozac® most commonly used SSRI) treatment during the last month of gestation on pregnancy complications, placental and neonatal health in a non-depressed sheep model. On day 119 ± 1 postbreeding (experimental day 0; E0) of a 151-day expected gestation, Hampshire ewes were randomly assigned to receive fluoxetine (n = 9 ewes, 15 lambs; daily intravenously treatment with 10 mg/kg on E0 and E1 and 5 mg/kg daily thereafter until parturition) or to a control group (n = 10; 14 lambs; vehicle only). Blood samples from ewes were collected throughout the experimental period and postpartum; blood from lambs were collected postpartum. Analysis of variance was used for statistical analysis. Fluoxetine treatment reduced placentome growth during the last month of pregnancy. Gestation length was decreased by 4.5 days in fluoxetine-treated ewes. Birthweight was reduced in lambs exposed to fluoxetine in utero; weights remained decreased until postnatal day 3. Placentome diameter by birthweight ratio was not different between groups suggesting that the decreased placentome diameter was accompanied by decreased lamb birthweight. During the first week postnatal, lambs exposed to fluoxetine in utero had decreased blood pH and decreased total carbon dioxide, bicarbonate, and base excess and increased lactate (days 3–6), collectively indicative of metabolic acidemia. Additionally, ionized calcium was decreased between postnatal days 0 to 4 in lambs exposed to fluoxetine in utero. Using a non-depressed animal model clearly defines a role for SSRI on the occurrence of perinatal complications and neonatal morbidity. The decreased placentome diameter, shortened gestation, decreased birthweight, decreased calcium levels, and neonatal acidemia suggest the occurrence of intrauterine growth restriction. The persistence of neonatal acidemia for several days postpartum suggests poor neonatal adaptation to extrauterine environment.

Increased milking frequency and incomplete milking have differential effects on milk yield and mammary gland physiology that are important for optimization of milking practices in dairy herds. The objectives of this experiment were to determine the effects of increased milking frequency and incomplete milking on milk production rate (MPR) and milk composition and to determine if milking 3 times daily (3×) could rescue the negative production effects of incomplete milking. Twenty-two multiparous cows were enrolled onto this experiment beginning at 5 days in milk (DIM) and continuing through 47 DIM. A split-plot design was used to randomize the 2 treatments, which were milking frequency and incomplete milking. Eleven cows were randomly assigned to be milked 2 times (2×) daily and 11 cows were randomly assigned to be milked 3×. Within each cow, a contralateral half-udder was randomly assigned to be incompletely milked (30% milk remaining in the gland; IM), and the other half-udder was randomly assigned to be milked completely (CM). Quarter-level milk yields were recorded at each milking session. Milk samples from all quarters were collected twice weekly at the beginning of the morning milking for analysis. Cows milked 2× tended to have reduced MPR compared with 3× milked cows (1.81 ± 0.06 vs. 1.97 ± 0.06 kg milk/h; P = 0.06). Half-udders that were CM and IM produced 1.09 ± 0.03 and 0.80 ± 0.03 kg milk/h, respectively. There was an interaction between incomplete milking treatment and week of lactation (P = 0.04). No interaction was detected between milking frequency and incomplete milking for MPR or milk components. Cows milked 3× had increased milk fat percent (1.93 ± 0.09% vs. 1.65 ± 0.09%, P = 0.047), decreased milk lactose percent (4.80 ± 0.04% vs. 4.93 ± 0.04%, P = 0.04), and exhibited no differences in milk protein percent or milk somatic cell count (SCC) compared with cows milked 2×. Half-udders that were IM had increased milk fat percent (2.15 ± 0.07% vs. 1.43 ± 0.07%, P < 0.0001), decreased lactose percent (4.75 ± 0.03% vs. 4.99 ± 0.03%, P < 0.0001), increased milk log10SCC (4.22 ± 0.05 vs. 4.41 ± 0.05, P = 0.0004), and no differences in milk protein percent compared with CM half-udders. These results indicate that a 3× milking frequency in IM half-udders was not able to improve milk production compared with IM half-udders milked 2×. Our results indicate that 30% milk remaining in the gland had an irreversible impact on milk yield as increased milking frequency was not able to reverse the milk yield lost.

The peripartal cow experiences a rapid change in calcium metabolism at the onset of lactation. Research has focused on understanding how mammary-derived factors, such as serotonin (5HT) and parathyroid hormone like hormone (PTHLH), aid in coordinating these calcemic adaptations to lactation. Therefore, the aim of our study was to determine how induced subclinical hypocalcemia influences physiological responses, specifically the 5HT-PTHLH-Ca axis, in lactating and nonlactating dairy cows to elucidate the potential contribution of the mammary gland. Twelve nonlactating, nonpregnant (NL) multiparous Holstein cows and 12 early-lactation (EL) multiparous Holstein cows received either (1) a continuous 24-h intravenous solution of 0.9% NaCl or (2) 5% ethylene glycol tetraacetic acid (EGTA) solution in 0.9% NaCl (n = 6 EL, n = 6 NL per treatment) with the aim of maintaining blood ionized calcium (iCa) less than 1.0 mM. Mammary gland biopsies were taken immediately after and 48 h after termination of infusion. Blood was sampled hourly during infusion and 4, 8, 12, 24, 48, and 72 h after termination of infusion. Infusion of EGTA successfully decreased blood iCa concentrations. However, EL EGTA-infused cows required increased rates of EGTA infusion to maintain iCa below 1.0 mM. Circulating and mammary serotonin concentrations were increased in EL relative to NL cows, with no difference as a result of EGTA infusion. Mammary PTHLH expression was increased in EL cows, with highest expression observed in EL EGTA-infused cows. Collectively, these data demonstrate the robust adaptations EL cows have to maintain Ca homeostasis and the supporting roles 5HT and PTHLH may play.

The monoamine serotonin has been shown to regulate peripartal calcium homeostasis in multiparous cows and be a possible mitigation tool for hypocalcemia. Increasing circulating serotonin concentrations via prepartum intravenous (IV) administration of the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) increases postpartum calcium concentrations. However, the ability of 5-HTP to be used orally or ruminally to alter circulating serotonin concentrations has not been established. Hence, our objective was to determine if ruminal administration of 5-HTP altered circulating serotonin concentrations. Four ruminally cannulated, nonlactating, nonpregnant multiparous Holstein dairy cows were randomly assigned to 1 of 4 treatments in a 4 × 4 replicated Latin square with 4-d periods separated by a 7-d washout. On d 1 and 2 of each period, cows were dosed with 1 of 4 experimental treatments as follows: (1) 0 mg/kg of body weight (BW) of 5-HTP, (2) 1 mg/kg of BW of intraruminal 5-HTP, (3) 2 mg/kg of BW of intraruminal 5-HTP, or (4) 1 mg/kg of BW of IV 5-HTP. Infusions were administered over a 1-h period, and all groups not receiving 5-HTP IV were infused with an equal volume of IV saline to that of IV 1 mg/kg of BW of 5-HTP treatment. Continuous serial blood samples were collected beginning after d 2 of treatment administration. Whole blood serotonin concentrations were higher in cows dosed with 2 mg/kg of BW of intraruminal 5-HTP immediately after dosing when compared with cows dosed with 0 mg/kg of BW of 5-HTP on d 2, but were similar on d 3 and 4 of the experimental period. Cows receiving IV 5-HTP had the highest circulating serotonin concentrations relative to all other treatments. These findings demonstrated that 2 intraruminal dosings of 5-HTP at 2 mg/kg of BW resulted in elevated circulating serotonin concentrations relative to the control immediately after dosing. This supports the potential for 5-HTP to be used orally to manipulate circulating serotonin concentrations.