Effectiveness of Stem Cells in the Treatment of Reproductive Functions and Fertility in Rats Exposed to the Endocrine Disruptor, Tributyltin

Abstract

Infertility is an important problem for its responsibility about many of personal suffering and marriage separation. Organotins (OTs) are a diverse group of widely distributed environmental pollutants that have been implicated as reproductive toxicants and endocrine disruptors, and mainly used as biocides in antifouling boat paints and in plastics industry as heat and light stabilizers for poly (vinyl chloride) PVC plastics. One of most toxic organotins is tributyltin (TBT). If these endocrine disrupters may mimic endogenous hormone activities, immature male rats would be more vulnerable during the pubertal period where sexual maturation and reproductive organs are still under development. Stem cells are non-differentiated cells that have the ability to proliferate, regenerate, and transform into differentiated cells and it has been reported that mesenchymal stem cells (MSCs), when transplanted systemically, it can home into the damaged site and finally differentiate into cells specific to the tissue. The target of this study is to evaluate the potential role of bone marrow mesenchymal stem cells in the restoration of fertility and reproductive functions in mature male rats after testicular dis-functions induced by one of the endocrine disrupters, tributyltin oxide (TBTO) in young rats. In this experiment, a total number of 115 of wistar rats (85-90 g. average body weight) and 84 female rats (140-150 g. average body weight) were used. To determine the half lethal dose (LD50) of TBTO, a total number of 40 male rats were used and calculated LD50 was found to be 0.25 mg/kg b.wt, 16 rats were used for dose selection and 1/4 of LD50 (0.062) mg/kg b.wt was selected during the experiment as the most dose that induced testicular dis-functions. 15 rats were used for isolation of mesenchymal stem cells (MSCs). Male rats were divided into 5 groups: Group 1 (-ve control): with no treatment. Group 2 (TBTO vehicles control): Rats were received orally 1ml distilled H2O containing 50µ ethanol, twice a week for 3 months. Group 3 (TBTO group): In order to induce testicular dis-functions. Rats were received orally 1ml dist. H2O containing 50µ ethanol and (0.062) mg/kg b.wt TBTO (1/4 of calculated LD50) twice a week for 3 months. Group 4 (TBTO and MSCs vehicles control): Rats were received orally 1ml distilled H2O containing 50µ ethanol, twice a week for 3 months, and then injected intravenously (IV) through the tail vein with a single dose of 0.5 ml phosphate buffer saline (PBS) per animal until 5 months. Group 5 (TBTO and mesenchymal stem cells group) (TBTO and MSCs): Rats which induced testicular dis- functions by receiving of (0.062) mg/kg b.wt TBTO (1/4 of calculated LD50) twice a week for 3 months, and then injected intravenously (IV) through the tail vein with a single dose of MSCs (3x106 cells in 0.5 ml saline) per animal until 5 months.