Abstract: Associations between the immune and endocrine systems during equine pregnancy remain poorly understood. Based on the hypothesis that distinct phases of the equine healthy gestation are characterized by specific associations between circulating immunological and hormonal parameters, contributing to pregnancy maintenance, this investigation aimed to: (i) evaluate how circulating immunological and hormonal parameters change across different phases of pregnancy; (ii) investigate associations between changes in circulating immunological and hormonal parameters; and (iii) propose potential hormonal drivers of immunological modulation during pregnancy. Peripheral blood samples were prospectively collected from mares (n = 8) before ovulation and during pregnancy at 30, 90, 150, 210, 240, 270, 300, and 330 days of their healthy gestations. An immunological panel included the distribution of circulating T cell (CD3, CD4, and CD8) and B cell subpopulations, complete blood counts (CBC), and serum protein profile. Hormonal analyses included equine chorionic gonadotropin (eCG), progestogens, androgens, estrogens, corticosteroids, and thyroid hormones. At 90 days, a statistically significant increase in peripheral blood CD4 T cell distribution was accompanied by a concomitant reduction in B cell distribution. This immunological modulation correlated positively with eCG, progesterone (P4), 5α-dihydroprogesterone (DHP), and estrone sulfate, and inversely with B cell levels. In contrast, at 210 days, B cell distribution peaked significantly while CD4 T cell distribution declined, concomitant with a rise in albumin levels. These changes positively correlated with cortisone and hematocrit. Mid-gestation was characterized by associations between different androgens and circulating T cell and B cell distributions. Consistent negative associations were observed between progesterone, DHP, and estradiol-17β with glucocorticoid metabolites throughout gestation. Estradiol-17β and IgM concentrations showed a positive correlation in late gestation. Immune-hormone and hormone-hormone associations were more pronounced during early and mid-gestation, while the final 100 days of pregnancy were characterized by relatively constant levels. Collectively, our findings suggest immune-hormone associations that potentially orchestrate immunomodulation, fetal development, successful pregnancy maintenance, and parturition in the mare.
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Overview
This study examined how immune system components and hormone levels interact during different stages of healthy pregnancy in mares (female horses).
It aimed to understand how these interactions contribute to maintaining pregnancy by analyzing blood samples collected throughout gestation.
Study Objectives
Evaluate changes in circulating immunological and hormonal parameters across different pregnancy phases.
Investigate the associations between these immunological and hormonal changes.
Identify hormonal factors potentially driving immune system modulation during pregnancy.
Methodology
Sample Collection:
Blood samples taken from 8 healthy mares before ovulation and at 30, 90, 150, 210, 240, 270, 300, and 330 days into pregnancy.
Immunological Analysis:
Measured distributions of T cells (CD3+, CD4+, CD8+ subsets) and B cells in peripheral blood.
Complete blood counts (CBC) and serum protein profiles were performed.
Hormonal Analysis:
Measured levels of equine chorionic gonadotropin (eCG), progestogens (progesterone and its metabolites), androgens, estrogens, corticosteroids, and thyroid hormones.
Key Findings
Early Gestation (around 90 days):
Significant increase in CD4+ T cell distribution in blood.
Concomitant decrease in B cell distribution.
These immune changes correlated positively with hormones eCG, progesterone (P4), 5α-dihydroprogesterone (DHP), and estrone sulfate.
Inverse correlation between B cell levels and the above hormones.
Mid-Gestation (around 210 days):
Peak in B cell distribution occurred simultaneously with a decline in CD4+ T cells.
Increase in serum albumin levels observed.
These changes positively correlated with cortisone (a glucocorticoid) and hematocrit levels (which reflect red blood cell concentration).
Associations between various androgens and lymphocyte subpopulations were noted.
Throughout Gestation:
Negative correlations found consistently between progesterone, DHP, and estradiol-17β with glucocorticoid metabolites, suggesting hormonal balance affecting immune regulation.
Late Gestation:
Positive correlation between estradiol-17β levels and IgM antibody concentration, indicating immune system activity before parturition.
Immune and hormonal parameters showed relative stability during the last 100 days of pregnancy.
Interpretation and Implications
The study identifies phase-specific patterns where immune cell populations and hormone levels are tightly linked, implying coordinated modulation for pregnancy success.
Early immunomodulation with increased helper T cells (CD4+) and decreased B cells, influenced by pregnancy hormones, might help tolerate the fetus.
Later shifts, such as increased B cells and glucocorticoid correlation, may prepare the mare’s immune system for childbirth and neonatal immunity.
Negative associations between progesterone/estrogens and glucocorticoids suggest a complex hormonal interplay regulating immune steady state.
The findings contribute to better understanding of reproductive immunology in horses, potentially aiding in managing pregnancy disorders or improving breeding programs.
Cite This Article
APA
Feijo LS, Ledeck J, Wolfsdorf K, Ponthier J, Parry S, Felippe MJB.
(2025).
Associations between immunological and hormonal parameters during healthy pregnancy in mares.
Theriogenology, 250, 117719.
https://doi.org/10.1016/j.theriogenology.2025.117719
Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary, Cornell University, Ithaca, NY, USA.
Ledeck, Joy
Equine Theriogenology, Equine Clinical Sciences Department, FARAH Comparative Veterinary Medicine, University of Liège, Belgium.
Wolfsdorf, Karen
Hagyard Equine Medical Institute, Lexington, KY, USA.
Ponthier, Jerome
Equine Theriogenology, Equine Clinical Sciences Department, FARAH Comparative Veterinary Medicine, University of Liège, Belgium.
Parry, Stephen
Cornell Statistical Consulting Unit, Cornell University, Ithaca, NY, USA.
Felippe, M Julia B
Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary, Cornell University, Ithaca, NY, USA. Electronic address: mbf6@cornell.edu.
MeSH Terms
Animals
Female
Horses / immunology
Horses / blood
Horses / physiology
Pregnancy
Pregnancy, Animal / immunology
Pregnancy, Animal / blood
Hormones / blood
Conflict of Interest Statement
Declaration of competing interest None of the authors have any conflict of interest to declare.