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Link to original content: https://pubmed.ncbi.nlm.nih.gov/36816179
The metabolic differences of anestrus, heat, pregnancy, pseudopregnancy, and lactation in 800 female dogs - PubMed Skip to main page content
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. 2023 Feb 2:10:1105113.
doi: 10.3389/fvets.2023.1105113. eCollection 2023.

The metabolic differences of anestrus, heat, pregnancy, pseudopregnancy, and lactation in 800 female dogs

Claudia Ottka  1   2   3   4 , Katariina Vapalahti  1   2   3 , Sebastian P Arlt  5 , Alexander Bartel  6 , Hannes Lohi  1   2   3   4
Affiliations

The metabolic differences of anestrus, heat, pregnancy, pseudopregnancy, and lactation in 800 female dogs

Claudia Ottka et al. Front Vet Sci. .

Abstract

Introduction: Reproduction causes major hormonal and physiological changes to the female body. However, the metabolic changes occurring during canine reproduction are scarcely studied.

Methods: In this cross-sectional study, we assessed the metabolic effects of canine reproductive status using a 1H NMR metabolomics platform optimized and validated for canine use. The study population consisted of a total of 837 healthy, intact female dogs in breeding age, of which 663 dogs were in anestrus, 78 in heat, 43 were pseudopregnant, 15 were pregnant, and 38 were lactating. The differences in metabolite profiles between these states were studied by the Kruskal-Wallis test with post-hoc tests performed using the Dunn's test, and visualized by box plots and a heatmap. The ability of the metabolite profile to differentiate pregnant dogs from non-pregnant ones was assessed by creating a multivariate Firth logistic regression model using forward stepwise selection.

Results: Lactation, pregnancy and heat all were associated with distinct metabolic changes; pregnancy caused major changes in the concentrations of glycoprotein acetyls, albumin and creatinine, and smaller changes in several lipids, citrate, glutamine, and alanine. Pseudopregnancy, on the other hand, metabolically largely resembled anestrus. Lactation caused major changes in amino acid concentrations and smaller changes in several lipids, albumin, citrate, creatinine, and glycoprotein acetyls. Heat, referring to proestrus and estrus, affected cholesterol and LDL metabolism, and increased HDL particle size. Albumin and glycoprotein acetyls were the metabolites included in the final multivariate model for pregnancy detection, and could differentiate pregnant dogs from non-pregnant ones with excellent sensitivity and specificity.

Discussion: These results increase our understanding of the metabolic consequences of canine reproduction, with the possibility of improving maternal health and ensuring reproductive success. The identified metabolites could be used for confirming canine pregnancy.

Keywords: dog; lactation; metabolism; metabolomics; pregnancy; reproduction.

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Conflict of interest statement

This study received funding from PetBiomics Ltd. The funder had the following involvement with the study: the salaries of CO and KV were funded by PetBiomics Ltd. CO and KV were employees and HL the board director and an owner of PetBiomics Ltd., a company that provided the used NMR metabolomics platform for dogs. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Measurands quantified using the validated (24) canine NMR metabolomics platform. BCAA, Branched-chain amino acids; HDL, High-density lipoprotein; LDL, Low-density lipoprotein; VLDL, Very low-density lipoprotein.
Figure 2
Figure 2
Overview of the used samples, inclusion criteria, data preprocessing, and statistical analyses utilized in this study. XL-VLDL, Very large very low-density lipoprotein; -FC, free cholesterol; -CE, esterified cholesterol; -PL, phospholipids, -TG, triglycerides; PCA, Principal component analysis; MAD, median absolute deviation.
Figure 3
Figure 3
Heatmap of the measurands significantly (p < 0.0026) associated with the reproductive state in the Kruskal-Wallis test. The colors represent the median of each reproductive state group in median absolute deviation (MAD) scaled data. The intensity of the color increases proportionally with the magnitude each reproductive state differs from the overall median metabolite value. The change in magnitude is expressed as the amount of MAD:s the median of each reproductive state group differs from the overall median of the metabolite. Blue hues indicate that the median MAD of the group is lower, and red hues indicate that the median MAD of the group is higher than the overall median of the dataset. The letters indicate similarity of groups: groups with the same letters do not differ significantly from each other, whereas groups with different letters differ significantly (p < 0.05) from each other for the metabolite in question in the Dunn's test with Bonferroni correction, which was performed as a post-hoc test for the Kruskal-Wallis test. Emboldened, black letters indicate significant differences from anestrus. Anestrus n = 663, heat n = 78, pseudopregnancy n = 43, pregnancy n = 15, lactation n = 38. BCAA, Branched-chain amino acids; GlycA, Glycoprotein acetyls; SFA, Saturated fatty acids. %, percentage of the molar concentration of total fatty acids. Fatty acids without the symbol % are derived from the absolute (mmol/l) concentration of the fatty acid in question. LDL, Low-density lipoprotein; HDL, High-density lipoprotein; VLDL, Very low-density lipoprotein; S, small; L, large; XL, very large.
Figure 4
Figure 4
Box plots of selected measurands with significantly different concentrations from anestrus in one or more of the other reproductive cycle phases according to the Kruskal-Wallis test. The black horizontal lines indicate the serum all dogs' reference intervals of the NMR method (Ottka et al. 2021). Anestrus n = 663, heat n = 78, pseudopregnancy (Pseudopreg.) n = 43, pregnancy (Preg.) n = 15, lactation n = 38. (A) Albumin, (B) Glycoprotein acetyls, (C) Creatinine, (D) Free cholesterol, (E) Glutamine, (F) Glycine.
Figure 5
Figure 5
ROC curve of the multivariate model for classification of pregnant dogs. The dependent variables included in this model were albumin and glycoprotein acetyls (GlycA). An area under the curve (AUC) nearing 100% is considered excellent. Test: receiver operating characteristic (ROC) curve, AUC, and its 95% confidence intervals (CI) in testing data (pseudopregnant n = 8, pregnant n = 3), used to test the model fit in a sample set independent from the training data. Note, that the CI for an AUC of 100% is not defined. Train: ROC curve, AUC, and its 95% CI in training data (pseudopregnant n = 35, pregnant n = 12), which was used to create the model. The testing and training datasets were randomly split prior to model generation from data including all pregnant (n = 15) and pseudopregnant (n = 43) dogs to cover 20% and 80% of the samples, respectively. AE: ROC curve, AUC, and its 95% CI in the data including dogs in anestrus (n = 663) and all pregnant (n = 15) dogs. This data was used to test the model in a larger dataset of female dogs.
Figure 6
Figure 6
Scatter plot of (A) pregnant and pseudopregnant dogs in the testing and training data and (B) dogs in anestrus based on albumin and glycoprotein acetyls (GlycA) concentration. The dashed line represents the decision threshold for a cutoff of 0.5 of the multivariate Firth logistic regression model. Dogs above the dashed line (the top left) would be classified as pregnant and dogs below it (down right) as non-pregnant.
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