Long-term effects of maternal mild hyperthyroidism on the development and the behavior of offspring in adulthood

MICHEL LARA, MARÍA CECILIA; SÁNCHEZ MARÍA BELÉN; NEIRA FLAVIA JUDITH; VIRUEL LUCIANA BELÉN; SOAJE MARTA; PIETROBON ELISA OLIVIA; GOMEZ SILVINA; JAHN GRACIELA ALMA; MACKERN OBERTI JUAN PABLO; VALDEZ SUSANA RUTH

Congreso; XL Reunión Anual de la Sociedad de Biología de Cuyo; 2022

Abnormal levels of thyroid hormones (THs) are associated with alterations in anxiety and circulating hormones such as glucocorticoids (GCs) and prolactin affecting fertility and reproductive success. However, little is known about the long-term effects of maternalhyperthyroidism on the development and behavior of their offspring. For this purpose, eight pregnant Wistar rats were divided in two groups defined as: Control (Euthyroid, n=4) and HyperT (n=4). Hyperthyroidism was induced with T 4 0.1mg/kg/day, s.c. After delivery,on day 2 of lactation, the number of pups in each litter was standardized to eight and the offspring allowed to growth under standard condition according to the NIH guide for the Care and Use of Laboratory Animals. Pup development parameters were recorded from birth to 42 postnatal day (PND). Adult female and male offspring (PND 85-100) were subjected to the Open Field Test (OFT) to evaluate locomotor activity using EthoWatcher computacional tool. The parameters assessed were as follows: a) rearings, b) entries to areas of interest, c) total distance traveled. At PND 100-120, the adult offspring were sacrificed, trunk blood was collected for serum hormonaldeterminations for ELISA and adrenal glands (AG) dissected for histological analysis using Image J program. We found that offspring from HyperT mothers (named HyperT pups) presented alterations in the postnatal development of some physical, sensory, motor, and l pups). Body length at PND 1 was lower in HyperT pups (p<0.001) while there were delays in the eye opening (p<0.01), ear canal opening (p<0.05), forelimb grasp (p<0.05), auditory startle(p<0.001), testicular descent (p<0.01), vaginal opening (p<0.05) in HyperT pups compared to Control pups. In the OFT, adult female and male pups showed different behaviours in locomotor activity and exploration: female HyperT pups exhibited greater distance traveled (p<0.01), increased number of entries to areas of interest (p<0.01) and of rearings (p<0.05) compared to Control female pups. In addition, female HyperT pups showed increased entries and time spent in the center of the square (p<0.01) and number of rearings (p<0.05) compared to male HyperT pups. At PND 100-120, we found an increased size of the AG zona fasciculata (GCs synthesis zone)in adult female HyperT pups compared to adult female Control pups (636,6  40,01 vs 451,0 10 arbitrary units p<0.01, while there was no differences between male of both group. Also, at PND 100-120 the basal serum corticosterone levels were similar in both male and female Control and HyperT rats. These results show that a maternal mild hyperthyroidism may have long- term effects on physical and neurological development of the offspring triggering sex-dependent behavioral consequences in adulthood.