Metabolomics during canine pregnancy and lactation.

During pregnancy and parturition, female dogs have to cope with various challenges such as providing nutrients for the growth of the fetuses, hormonal changes, whelping, nursing, milk production, and uterine involution. Metabolomic research has been used to characterize the influence of several factors on metabolism such as inter- and intra-individual factors, feeding, aging, inter-breed differences, drug action, behavior, exercise, genetic factors, neuter status, and pathologic processes. Aim of this study was to identify metabolites showing specific changes in blood serum at the different phases of pregnancy and lactation. In total, 27 privately owned female dogs of 21 different breeds were sampled at six time points: during heat, in early, mid and late pregnancy, at the suspected peak of lactation and after weaning. A validated and highly automated canine-specific NMR metabolomics technology was utilized to quantitate 123 measurands. It was evaluated which metabolite concentrations showed significant changes between the different time points. Metabolites were then grouped into five clusters based on concentration patterns and biochemical relationships between the metabolites: high in mid-pregnancy, low in mid-pregnancy, high in late pregnancy, high in lactation, and low in lactation. Several metabolites such as albumin, glycoprotein acetyls, fatty acids, lipoproteins, glucose, and some amino acids show similar patterns during pregnancy and lactation as shown in humans. The patterns of some other parameters such as branched-chain amino acids, alanine and histidine seem to differ between these species. For most metabolites, it is yet unstudied whether the observed changes arise from modified resorption from the intestines, modified production, or metabolism in the maternal or fetal tissues. Hence, further species-specific metabolomic research may support a broader understanding of the physiological changes caused by pregnancy that are likely to be key for the normal fetal growth and development. Our findings provide a baseline of normal metabolic changes during healthy canine pregnancy and parturition. Combined with future metabolomics findings, they may help monitor vital functions of pre-, intra-, and post-partum bitches and may allow early detection of illness.

Thyroid hormones in canine pregnancy and lactation.

It is believed that thyroid function has a significant effect on fertility and fetal development in mammals. So far, however, only few studies have been published about potential effects of the reproductive cycle stage on thyroid hormone concentrations in dogs. Therefore, over the course of 122 pregnant and non-pregnant cycles in healthy bitches, Thyroid stimulating hormone (TSH), free Thyroxine (fT4), total Thyroxine (tT4) and Progesterone (P4) were measured six times to assess the influence of the cycle stage and pregnancy on hormone concentrations. The aim was to evaluate established reference intervals for the thyroid hormones in a female study population. Of the 122 bitches, 98 became pregnant. Blood samples were collected during estrus, three times in pregnancy, during lactation and after weaning, or at equivalent times during and after estrus in non-pregnant dogs. No differences between pregnant and non-pregnant animals in any of the thyroid hormones were found. Hormone concentrations, however, differed significantly between the six samplings (p < .01). TSH initially declined during pregnancy, then rose again. The mean concentration of all dogs exceeded the overall upper reference limit of 0.70 ng/mL during lactation. Concentrations of tT4 and ft4 increased during the first third of pregnancy and then subsequently declined. The overall reference limits for tT4 were 0.47-3.20 µg/dL, and for fT4 4.86-29.60 pmol/L, but the reference intervals varied between the sampling dates. The observed patterns may reflect that maternal tT4 and fT4 seem to have important effects during early pregnancy, including a pronounced negative feedback effect on TSH. The initial increase and subsequent decline of tT4 and fT4 concentrations during the course of pregnancy is in accordance with findings in humans and may support the development of fetal thyroid function. The observed peak of TSH concentrations during lactation suggests that the demand for thyroid hormones in this phase is largest. Even if the underlying causes and mechanisms of thyroid regulation are not fully understood, the results of this study show relevant changes of hormone concentrations in the course of the sexual cycle and pregnancy. In that regard, cycle stage needs to be considered when assessing thyroid function in bitches.

Progesterone Concentrations during Canine Pregnancy.

Pregnancy and lactation are amongst the most challenging times of a bitch's life. Most studies focusing on the endocrinological aspect of pregnancy consider only a small number of animals. The aim of this study was to evaluate progesterone (P4) concentrations in a large number of bitches during early, mid and late pregnancy. In total, 126 bitches of various breeds were recruited following a thorough clinical and gynecological examination during estrus. Blood samples were collected three times (T1-T3) during pregnancy or from non-pregnant dogs in diestrus, and P4 was measured via chemiluminescence. At T1 (11-19 days post-ovulation (dpo)), serum P4 concentrations were 30.23 ± 6.65 ng/mL and 28.45 ± 6.26 ng/mL, at T2 (23-32 dpo) they were 22.73 ± 6.27 ng/mL and 22.59 ± 5.77 ng/mL and at T3 (52-60 dpo) they were 6.68 ± 2.18 ng/mL and 3.17 ± 2.26 ng/mL, in pregnant (n = 98) and non-pregnant (n = 23) dogs respectively. The P4 concentrations differed significantly between pregnant and non-pregnant animals at the last examination (p ≤ 0.001). In the context of hypoluteoidism, the gathered data yielded interesting results. Overall, 28 out of 98 pregnant bitches showed a greater decline (>15 ng/mL) in P4 concentrations from early to mid-pregnancy, and 56 bitches showed P4 concentrations lower than deemed adequate (>20 ng/mL at T1 and T2, >5 ng/mL at T3) according to existing recommendations. Despite not being supplemented with P4, none of those animals suffered from abortion or preterm delivery. Considering that supplementation of P4 can entail considerable risks for the bitch and the puppies, more research on P4 concentration patterns, diagnosis of hypoluteoidism and treatment indications and options is indicated.