Age-Related Dynamics of Liver Morphometric Changes and Hemostasis Parameters in Rats Following Prenatal Hypoxia
Gulnar Jafarova1* , Sevinj Yusifova1 , Nargiz Mahmudova1 ,
Aynur Qaflanova2 , and Gunay Hajiyeva2
Abstract. To study the long-term consequences of severe intermittent prenatal hypoxia on liver structure and hemostatic system dynamics in rats at different postnatal developmental stages. Pregnant Wistar rats were exposed to normobaric hypoxia (5% O₂, 20 min/day) during embryonic, pre-fetal, or fetal gestation periods. Liver morphometric parameters (hepatocyte and nuclear areas, nuclear-cytoplasmic ratio) and hemostatic indicators (fibrinogen, activated partial thromboplastin time [aPTT], and plasma heparin tolerance [PHT]) were evaluated in offspring at 1, 3, and 6 months of age. At 1 month, hypoxia-exposed animals showed a 19–25% liver mass decrease versus controls (p < 0.001), hydropic hepatocyte degeneration, increased cell size, and systemic hypocoagulation. By 3 and 6 months, hepatocyte and nuclear sizes normalized. However, relative liver mass remained elevated (p < 0.01), with histology revealing persistent sinusoidal congestion and venous stasis. Concurrently, an age-related inversion from hypocoagulation to a procoagulant state occurred. In 6-month-old rats, fibrinogen increased, aPTT shortened, and PHT decreased to 56–77% of control values (p < 0.01). Severe prenatal hypoxia induces a biphasic adaptive response. Despite morphometric parenchymal recovery, hepatic vascular remodeling and microcirculatory disorders persist into adulthood, likely driving the development of a long-term procoagulant phenotype.
Keywords: blood coagulation, fetal programming, hepatocytes, microcirculation, venous stasis