Testosterone enhancement during pregnancy influences social coping and gene expression of oxytocin and vasopressin in the brain of adult rats

Abstract

Steroid hormones are important mediators of prenatal maternal effects and play an important role in fetal programming. The aim of our study was to investigate how testosterone enhancement during pregnancy influences neurobehavioral aspects of social coping of rat offspring in adulthood. Pregnant rat dams were exposed to depot form of testosterone during the last third of pregnancy (i.e., beginning on the 14 th day of pregnancy). Their adult offspring were later tested in a social interaction test and expression of oxytocin and arginine-vasopressin mRNA in the hypothalamic nuclei was evaluated. Our research showed that prenatal exposure to higher levels of testosterone activated socio-cohesive and socio-aversive interactions, but only in males. The testosterone-exposed group also showed decreased oxytocin mRNA expression in the supraoptic and paraventricular nuclei of the hypothalamus, and increased arginine-vasopressin mRNA expression in the supraoptic and suprachiasmatic nuclei as compared to controls. However, we did not observe any sex differences in the expression of oxytocin and arginine-vasopressin mRNA in these regions. Our findings show that testosterone enhancement in pregnancy could have long-lasting effects on oxytocin and arginine-vasopressin levels in the brain of adult animals, but lead to changes in behavioral aspects of coping strategies only in males.

Oxytocin and Pregnancy

“…In 1993, Broad et al [24] demonstrated that pregnant sheep exposed to progesterone had more OT mRNA in the paraventricular and supraoptic nuclei of the hypothalamus, while those exposed to estrogen didn't show significant growth in the supraoptic nuclei. However, testosterone enhancement during pregnancy brought about decreased oxytocin mRNA expression in the paraventricular nuclei of pregnant rats [25]. Estrogen and testosterone may play an opposite role in the central OT system.…”

Effects of prenatal testosterone exposure on the development of autism‐like behaviours in offspring of Wistar rats

“…According to some research findings (Auyeung et al, 2009; Bakker‐Huvenaars et al, 2018; Xu et al, 2013), autism spectrum disorders are associated with increased testosterone and decreased oxytocin, whereas psychotic affective disorders like schizophrenia are associated with increased oxytocin and decreased testosterone (Crespi, 2016). The oxytocin and testosterone systems interact directly on a molecular and physiological level in humans and rats, leading to opposite, antagonistic responses (Dai et al, 2017; Dzirbíková et al, 2018; Khan et al, 2018; Nicholson & Jenkin, 1995). None of the aforementioned investigations, however, investigated the social behaviour patterns or human brain.…”

Controversies involving the use of SSRIs during pregnancy and the increased risk of having a child with autism spectrum disorders – a case report and literature review

“…Besides, the results of the most recent studies indicate the lowered oxytocin and increased testosterone levels in the placenta of mothers with offspring who developed ASD [55]. Animal models and studies on humans provide the data indicating that increased testosterone levels during pregnancy negatively affect the levels of oxytocin and increases the risk of ASD [56], which might be partially associated with a more frequent incidence of ASD in male children [57].…”

“…Dodatkowo wyniki badań wskazują na zmniejszony poziom oksytocyny i zwiększony poziom testosteronu w łożyskach matek u potomstwa, u którego rozwinął się ASD [55]. Zwierzęce modele i badania na ludziach również dostarczają dowodów na to, że zwiększony poziom testosteronu w ciąży wpływa negatywnie na poziom oksytocyny i zwiększa prawdopodobieństwo rozwoju ASD [56], co po części może tłumaczyć częstsze występowanie ASD u dzieci płci męskiej [57].…”