Semester of Graduation

Summer 2025

Degree

Master of Science (MS)

Department

Animal Sciences

Document Type

Thesis

Abstract

While consequences of equine obesity are well defined, the extent to which persistent hyperleptinemia and accompanying leptin (Lep) resistance affect the fetal-maternal environment warrants further exploration. This study compared endocrine, fetal, placental, and uterine parameters during early pregnancy (through day 70) in mares with elevated leptin versus normal leptin (NL) concentrations. Fourteen mares were classified as either NL (n = 6; Lep 0.9 ± 0.3 ng/mL), moderate leptin (ML; n = 4; Lep 3.0 ± 0.3 ng/mL), or high leptin (HL; n = 4; Lep 5.8 ± 0.7 ng/mL) based on annual plasma leptin. Mares were artificially inseminated and induced to ovulate. Blood was collected serially through day 70 to monitor progesterone and equine chorionic gonadotropin (eCG). On day 70, fetuses were collected transcervically for morphometric measurements, and placental and endometrial tissues were snap-frozen for transcriptomic analysis. No differences were observed in embryonic vesicle diameter (days 14–25), fetal crown-rump length, fetal weight, or placental membrane weight between the three groups. Equine chorionic gonadotropin (eCG) levels were elevated from day 45 to 70 without group differences. Progesterone was significantly lower in both ML and HL mares on day 35 (P = 0.02) and greater in ML mares on day 70 (P = 0.02). Transcriptomic analyses revealed differential expression of 681 genes in the allantochorion, 1,506 in the gravid horn, and 2,796 in the non-gravid horn across leptin groups. Pathway enrichment analyses identified changes related to lipid metabolism, immune modulation, and angiogenesis. Notably, genes associated with cholesterol biosynthesis and transport (e.g., DHCR24, APOD, PLTP), pro- and anti-inflammatory signaling (e.g., CD81, NCF2, TLR4, HMGB1), and vascular remodeling (e.g., VEGFC, ANGPT1, PDGFD) were differentially expressed. Despite no observable differences in fetal biometry or eCG secretion during the first 70 days, mares with elevated leptin exhibited distinct endocrine and transcriptomic profiles indicative of metabolic stress, inflammation, and disrupted placental angiogenesis. These findings suggest that persistently elevated leptin may prime the uterine and placental environment for future dysfunction, even in the absence of early fetal growth restriction. Further investigation is needed to determine whether these changes persist and affect pregnancy outcomes later in gestation.

Date

7-16-2025

Committee Chair

Oberhaus, Erin

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