Effect of the induction of transgenerational obesity on maternal-fetal parameters

Abstract

Maternal obesity can cause complications for both women and their offspring for generations. Therefore, we intended to verify the repercussions of induction of transgenerational obesity on biochemical parameters, reproductive performance, and congenital anomaly frequency in Wistar rats. Female rats were used from successive generations. The female rats of parental generation (F, n=10) were mated to obtain their offspring (F generation). F female rats received a monosodium glutamate (MSG) solution to induce obesity (n=07) or vehicle (control, n=06) during the neonatal period. These adult female rats were classified as normal or obese using the Lee Index, mated, and delivered offspring (F generation), which were also evaluated for obesity using the Lee Index in adult life (FMSG, n=13, born from obese dams) or non-obesity status (FControl, n=12, born from control dams), and were mated in adulthood. During pregnancy, glycemia and an oral glucose tolerance test (OGTT) were analyzed. At term pregnancy, the females were sacrificed for serum biochemical profile, maternal reproductive outcomes, and fetal development. In FMSG rats, body weight gain at early pregnancy, glycemia by OGTT, total cholesterol, high-density-lipoprotein, and alanine transaminase activity were higher compared with those of FControl rats. FMSG rats also presented a lower implantation number and gravid uterus weight, increased pre-implantation loss and anomaly frequency in their fetuses (F generation) compared with those of FControl rats. Therefore, even without significant changes in body weight gain, obesity was established at the end of pregnancy of Wistar rats using other biomarkers. Additionally, these rats showed multiple adverse reproductive outcomes, confirming the deleterious effects that lead to obesity.

Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring

“…For obesity induction, male neonatal Wistar rats received 4 mg/g body weight subcutaneous (sc) injections of MSG (Sigma-Aldrich, USA) on days 2, 4, 6, 8, and 10 of postnatal life. Control Wistar rats received subcutaneous injections of saline solution (0.9% NaCl) on the same days ( 6 , 9 ). Both groups were weaned at 21 days of age and maintained in controlled conditions.…”

“…The Lee index was applied to all the male rats at 90 days of life. This index is defined as the cube root of body weight (g) × 10 / naso-anal length (cm) and values >0.300 are classified as obese ( 6 , 9 ). All obese animals included in the MSG group were defined as F1 generation.…”

“…In this context, parental health or exposures can affect the lifetime health outcomes of offspring ( 4 , 5 ). Since maternal effects have been the focus of the transgenerational transmission of metabolic disorders ( 5 – 9 ), the role of paternal obesity in offspring metabolic programming has been investigated but still not fully elucidated ( 8 , 10 ).…”

“…Experimental models might contribute towards understanding the pathophysiological mechanisms and consequences concerning transgenerational obesity ( 6 , 9 ). When administered to neonatal rats, monosodium glutamate (MSG) is recognized to cause obesity and clinical manifestations of metabolic syndrome ( 6 , 11 ).…”

Congenital Anomalies Programmed by Maternal Diabetes and Obesity on Offspring of Rats

“…For the obesity parameter, Lee Index was obtained at days 0 and 17 of pregnancy, and defined as the cube root of body weight (g) 10/nasoanal length (cm), for which a value equal to or <0.300 was classified as normal. Rats presenting values higher than 0.300 were classified as obese (Bernardis and Patterson, 1968;Soares et al, 2017). At term pregnancy (day 21), the female rats were anesthetized with sodium thiopental (Thiopentax R , intraperitoneal route, 120 mg/kg according to protocols of Ethical Committee), and, after confirming the signs that showed successful anesthetic procedure, the animals were decapitated to obtain blood samples.…”