Haematological Profile in Chronically Undernourished Thrifty Rats at 28 Days of Age

Foetal programming due to undernutrition is a known risk factor for the worldwide epidemic of Type 2 diabetes and cardiovascular disease.Total leukocyte count (6.9 vs. 12.7x 103/μL ; p<0.0001, n=6, U vs. C) and Lymphocytes (36.5% vs. 67.7%; p<0.0001, n=6, U vs. C) was significantly lower but granulocytes was significantly higher (21.1% vs. 69.9%; p<0.0001, n=6, U vs. C ) in the undernourished colony, RBC content (7.7 vs. 9.4 x 1012/L;, p< non significant,n=6, U vs. C) Hb (11.5g/ dl vs 14.8g/dl; p<0.0001, n=6, U vs. C) and Hematocrit (39.05% vs. 47.11%; p<0.0001, n=6, U vs. C ) were less but with a high RBC distribution width (11.99 vs. 13.36,p<0.0001,n=6,U vs. C). Platelet count (424.3 vs. 602.3 x 103/microliter, p<0.001, n=6, U vs. C) and Mean platelet volume (5.9 vs. 6.1 fL p< 0.01, n=6, U vs. C) were lower in the undernourished colony. This is indicative of a state of anaemia, an inflammatory process and a hypoplastic bone marrow. Introduction Developing countries like India face a burden of Type 2 Diabetes Mellitus, microand macro-vascular disease and cancer (Echouffo-Tcheugui 2012). There is increasing evidence from worldwide studies that have shown that these diseases occur due to impaired intrauterine growth (IUGR) and development (Godfrey and Barker 2000) . Experimental studies in a variety of animals have shown that this occurs due to “programming”, wherein an insult during the intrauterine life causes permanent changes in the development of a variety of tissue and organ systems. These alterations include a variety of cellular, structural, chemical, metabolic and hormonal adaptations to the undernourished environment during fetal life (McMillan and Robinson 2005). A variety of clinical studies have confirmed these observations. The studies carried out by David Barker and C.S. Yajnik provide evidence for the role of undernutrition in fetal programming especially in the Indian scenario. The Thin-Fat Indian phenotype as seen in the Pune Maternal Nutrition Studies has highlighted the role of body composition. Indian babies have the third lowest birth weight in the world, are insulin resistant, centrally obese but have a lower soft tissue weight. This phenotype is present at birth and is probably programmed through many generations of undernutrition (Yajnik, Fall et al 2003). Similar observations by have been made in a Wistar rat model (Thrifty Jerry) that has been chronically undernourished for more than 50 generations. The rats were insulin resistant, centrally obese, had higher homocysteine, endotoxin and leptin levels but lower adiponectin, vitamin B12 and folate levels.Exposure to streptozotocin, a selective β cell toxin showed an eight-fold increased susceptibility to diabetes. These animals also showed a reduction in soft tissue growth especially in muscle, heart, liver and the pancreas (Hardikar et al 2015). A restricted diet has also shown a disturbed hematopoietic environment in the bone marrow leading to hypocellularity, necrosis, and extracellular matrix modifications in undernourished animals (Travlos GS (2006), Fried W et al (1978), Vituri CL(2000), Prestes-Carneiro et al (2006) and Borelli P et al(1995). However, the effect of multigenerational undernutrition on the haematological profile has not been evaluated. In this study we looked at the effect of multigenerational undernutrition on the blood cell count in 28 day pups. Materials and Methods The study was carried out in pups from a multigenerationally (50 generations) undernourished wistar rat colony. The colony was undernourished for proteins, fats, fiber, vitamins and received a 50% isocaloric diet. (Hardikar et al 2015). The control group received a standard rat feed. Blood was collected from 28 day pups by retro-orbital bleeding and serum was immediately separated and analysed for Complete Blood Count (CBC) on an autoanalyser (Mindray BC2800 ). The study was ethically approved by the institutional ethics committee. Statistical Analysis All estimations were carried out in triplicates and values are expressed as +/Std Error of Mean (SEM). The statistical significance was evaluated by the unpaired t test using GraphPad Prism 6 version software. Results Table 1: Complete Blood Counts in Control and Undernourished (Thrifty Jerry) Wistar Rat Pups (28 Day) Parameter Undernourished Control TLC ( x 103/μL) *** 6.9 ± 0.7016 12.7 ± 1.519 Lymphocytes % **** 36.5 ± 4.280 67.7 ± 4.020 Granulocytes % **** 69.9 ± 3.301 29.13 ± 3.861 Monocyte % 3.05 ± 0.1258 3.16 ± 0.1764 RBC Count ( x 106/μL) 7.74 ± 0.7441 9.39 ± 0.2817 Hb (g/dl) **** 11.5 ± 0.4359 14.8 ± 0.3180 RBC distribution width *** 11.99 ± 0.1370 13.36 ± 0.2881 Platelet Count ( x 103/ μL) ** Mean platelet Vol (fL)* 424.3 ± 42.89 5.960 ± 0.05099 602.3 ± 51.34