Role of TNF-α in prenatal alterations in dams of mice under thermal stress

Abstract

The possible involvement of cytokines such as tumour necrosis factor-a (TNF-a), interleukin-1b (IL-1b) and interferon-g (IFN-g) that are suspected of causing pregnancy loss and miscarriage has been investigated in dams of mice subjected to hyperthermia. Thermal stress was induced by exposing mice dams at 40721C for 4 h every day during the different phases of the gestation period whereas the normothermic animals were housed at 22721C. The effect of maternal thermal stress was measured in pregnant mice at different phases of the gestation period namely, blastogenesis-implantation phase (days 0-5 postconceptionem [p.c.]), organogenesis or embryogenesis phase (days 6-15 p.c.) and fetogenesis phase (days 16-20 p.c.). Uterine examination of dams subjected to hyperthermia on days 6-15 p.c. showed maximum reduction in live fetus number, gestational index and maximum pre-and postimplantation loss in comparison with dams housed in normothermic environment and dams exposed to thermal stress between days 0-5 and 16-20 p.c. Maximum resorption rate and number of non-viable fetuses were observed in dams exposed to hyperthermia during days 6-15 p.c. Elevated levels of TNF-a and IL-1b were observed in the amniotic fluid of dams subjected to hyperthermia during days 6-15 p.c. but IFN-g levels remained unaltered. Single intraperitoneal (i.p.) administration of recombinant mouse TNF-a at a dose of 1 and 0.5 ng/ mice in dams on day 6 in normothermic condition resulted in a reduced number of live fetuses. Administration of anti-TNF-a antibody i.p. at a dose of 10 mg/dam on day 6 p.c. and subjected to thermal stress between days 6-15 p.c. increased marginally the number of fetuses but failed to attain statistical significance in comparison with days 6-15 p.c. thermally stressed dams without antibody treatment. It is concluded that the induction of TNF-a, in the amniotic fluid is associated with thermal stress during pregnancy and may be linked to the reproductive performances of dams. This study will help in understanding the mechanism of thermal injury in pregnant subjects.

Maximum apparent temperature lowers birth weight and increase hazards of preterm birth in a constant high ambient temperature exposed population in Piura, Peru

“…It is postulated that one of the mechanisms by which temperature affects pregnancy is by promoting an in ammatory state of the placenta (21). It is possible that this mechanism is more relevant during the third trimester of gestation, since it is during this stage that the growth rate of the fetus is higher, thus explaining why we found a greater decrease in birth weight in this window of exposure, like other studies.…”

La temperatura máxima aparente se asocia con un menor peso al nacer, en una población expuesta a una temperatura ambiente alta y constante en Piura, Perú

“…Se postula que uno de los mecanismos por los que la temperatura afecta al embarazo es promoviendo un estado inflamatorio de la placenta (20) . Es posible que este mecanismo sea más relevante durante el tercer trimestre de gestación, ya que es durante esta etapa cuando la tasa de crecimiento del feto es mayor, explicando así por qué encontramos una mayor disminución del peso al nacer en esta ventana de exposición, al igual que otros estudios.…”