Maternal exposure to tributyltin alters female reproductive system development

Abstract: Tributyltin (TBT) is a toxic compound used in antifouling paints and known for its endocrine-disrupting properties, including female reproductive dysfunction. We hypothesized that TBT exposure during gestation and lactation induces long-term reproductive alterations in female offspring. Pregnant Wistar rats were orally exposed from gestational day 7 to the end of lactation to 0.01% ethanol (control), TBT 100 ng/kg, or TBT 1000 ng/kg body weight. Female offspring were evaluated at postnatal days (PND) 21, 45, and 180 for biometric, hormonal, and ovarian parameters. Birth weight was reduced in the TBT100ng group, and body weight was reduced by PND180 in the TBT1000ng group. At PND45, testosterone increased in both TBT groups, while FSH decreased in the TBT100ng group. Estrous cyclicity irregularities, such as a prolonged metestrus-diestrus phase, were noted in the TBT1000ng group. Ovarian analysis showed increased cystic and atretic follicles at PND21 and PND45. Reduction in primordial follicles (TBT100ng) and corpora lutea (both TBT groups) was observed at PND180, along with ovarian fibrosis. TBT exposure led to age- and dose-dependent disruptions in ovarian follicle dynamics: initial increases in healthy follicles at PND21, followed by elevated unhealthy follicles and reduced healthy ones at later stages. At PND21, both TBT doses increased ERα expression, while TBT100ng increased AR expression. These changes were accompanied by a persistent increase in ovarian mast cells and elevated IL-6 protein expression, particularly at PND21 and PND180. Thus, maternal TBT exposure disrupts ovarian development and function, potentially increasing susceptibility to abnormal conditions such as polycystic ovary syndrome and primary ovarian insufficiency later in life.