HUMAN DOSES OF DEHP DURING PREGNANCY INFLUENCE POST-NATAL GROWTH AND REPRODUCTION IN OFF-SPRING FEMALE MICE

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is an endocrine-disrupting chemical that interferes with reproductive function and hormone regulation. Among different exposure routes (oral ingestion, inhalation, and dermal contact), the most common routes of exposure are via oral ingestion from food packaging and the use of cosmetic products, but high levels of phthalates are also present in household dust. Thus, exposure to phthalates is ubiquitous in human populations. For the general population, it was estimated that the average total daily individual ambient exposure to DEHP ranges from 0.21 to 2.1 mg/day. Thus, the estimated range of daily human exposure to DEHP is 3–30 μg/kg/day based on urinary metabolite concentrations; however, measurements of DEHP in household dust can reach up to 700 mg/kg, potentially increasing exposure levels in certain individuals. The effect of phthalate on male reproduction is now well studied; however, the effect of phthalate on female reproduction warrants extensive investigation. Because women are exposed to phthalates at a higher level than men through their widespread use of personal care and cosmetic products, In addition, it is hypothesized that phthalate can cross the placenta and interfere with the embryo, postnatal growth and development, and the later life of offspring after parturition. In this study, the Swiss albino female mice were randomly divided into four groups namely T0 (control), T1 (2mg/kg DEHP), T2 (4mg/kg DEHP), and T3 (6 mg/kg DEHP). Mating‟s strategy was followed by two virgin females and one stud male, who were confirmed pregnant by observing a vaginal plug. DEHP was exposed from the plug confirmed to parturition. After parturition, litter size (number of pups), litter weight, weight/pups, and body weight took until sexual maturity, then evaluated the reproductive cyclicity, the hormonal profile, hematological parameters, and organ developments after sexual maturity of female mice. The result showed that from birth to weaning, offspring of the T1 group exhibited a significantly body weight gain compare to the T0 group. On the other hand, considering weaning to sexual maturity, the rate of body weight gain was higher in the T1 and T2 groups compared to the T0 group. The final body weight was higher in the T2 group compared to the offspring of the T0 group. The estrous cyclicity data revealed that the rate of estrous in the T1, T2, and T3 groups were gradually decreased compared to the T0 group, in case of proestrus T1 was increased compared to T0 group but T2, T3 group were decreased compared to T0 group. The rate of diestrus in the T1, T2 and T3 groups were increased compare to the T0 group. On the other hand the rate of metestrus in the T1 and T2 group were decreased compare to T0 group but T3 was increased compared to T0 group. In the hormonal assay, the percentage of estrogen in the T1, T2 and T3 were gradually decreased compared to T0 group and the percentages of progesterone levels in the treatment groups were decreased significantly. Hematological parameters showed that the platelets in the T1, T2, and T3 groups were significantly higher than T0 group. In the term of neutrophil percentage, the T3 group was significantly lower than the other groups, Lymphocyte percentage in the T1, T2, and T3 groups were significantly higher than the T0 group. In case of total WBC count in the T1, T2 and T3 groups were increased compared to T0 group. The hematological parameters of PCT, RDW-CV, and RDW-SD were significantly lower in the T1, T2, and T3 groups than the T0 group. The percentage of monocytes in the T1, T2 and T3 were gradually decreased compared to T0 group. In cases of organ development, lung weight in the T1 and T3 groups were significantly increased from the T0 group but the T2 group was decreased from T0 group. In the T1, T2 and T3 groups, kidney and liver weight were significantly higher than in the T0 group. Heart weight in the T2 and T3 groups were significantly higher than in the T0 group. In the same way, spleen weight is comparatively higher in the T1 and T2 groups compared to the T0 group. There were no significant changes in the thyroid, uterus, or ovaries. Visual observation of the morphological characteristics of different organs showed that slight discoloration of the liver and lung was substantially affected in T3 group compared to T0 group.