Name: PRISCILA LANG PODRATZ
Publication date: 11/10/2018
Advisor:
Name |
Role |
|---|---|
| ELISARDO CORRAL VASQUEZ | Co-advisor * |
| JONES BERNARDES GRACELI | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| BRENO VALENTIM NOGUEIRA | External Examiner * |
| ELISARDO CORRAL VASQUEZ | Co advisor * |
| GIRLANDIA ALEXANDRE BRASIL AMORIM | External Examiner * |
| JONES BERNARDES GRACELI | Advisor * |
| LÍVIA CARLA DE MELO RODRIGUES | Internal Examiner * |
Pages
Summary: Organotin compounds (OTs) such as tributyltin (TBT) are environmental pollutants, with human exposure occurring mainly through the ingestion of contaminated shellfish. These chemical agents act as endocrine disruptors in marine invertebrates and also in rodents, affecting mainly the reproductive function and the lipids and carbohydrates metabolism. OTs can accumulate in the placenta and be transferred to fetuses. However, there is still no biotransfer model of OTs for mammals and rather few data on the gestational period and offspring. This study aims to evaluate the genesis and mechanisms involved in the reproductive and energy status alterations in adult female rats, placental dysfunction and fetal impairment in both genders, induced by direct exposure and maternal multigenerational inheritance through the ingestion of OTs-contaminated molluscs. Three-months-old female Wistar rats were divided into three groups: daily treated with vehicle (distilled water, control, CON), with Leucozonia nassa molluscs without OTs (LNN, 600 mg / day collected at Aracruz Beach, Espirito Santo, area without OTs contamination), or Leucozonia nassa with imposex (LNI, 600 mg / day, collected at Ilha do Frade Beach, Vitória, Espirito Santo, area contaminated with OTs), for 15 days, via gavage. Some of the animals were used for the evaluation of reproductive morphophysiology, with the remaining ones being allocated with control males for mating and subsequent cesarean section on the 20th gestational day, for the analysis of gestational parameters and collection of the placenta and fetuses. Adult LNI rats showed increased serum tin concentration, evidencing the transfer of OTs through the intake of contaminated molluscs. LNI rats developed irregularities in the estrous cycle; elevation of estrogen, progesterone and testosterone levels; ovarian folliculogenesis disorders and deposition of perifollicular collagen; hypertrophy of the luminal epithelium with pseudostratified areas, inflammatory process, increased collagen deposition and increased expression of uterine ERα. Regarding fertility parameters of the LNI group, we observed delays in establishing pregnancy, reduction in litter frequency, decrease in the number of implantations and consequent increase in pre-implantation embryo losses. Pregnant LNIs showed increased lipid profile, with hepatic accumulation of round lipid vacuoles with clearly-defined boundaries and variable sizes. Placentas from LNIs displayed increases in weight and percentage of glycogen cells, which is associated with higher expression of GLUT1 and with glucose transfer through the umbilical cord; accumulation of lipids (triglycerides and total cholesterol), with higher cholesterol supply to the fetuses; inflammatory process; higher expression of the regulatory proteins IRβ, p-Akt and p-mTOR. LNI fetuses of both genders exhibited higher body weight, increased megakaryocytes, lipids and oxidative stress in the liver. According to these findings, female rats directly exposed to OTs through the ingestion of contaminated molluscs revealed features of polycystic ovary syndrome. This endocrine disruption impairs placental formation and the expression of placental nutrient transporter, resulting in fetal anthropometric and hepatic disorders, due to adaptive responses to maternal influence.
