Transcriptome Sequencing in the Preoptic Region of Rat Dams Reveals a Role of Androgen Receptor in the Control of Maternal Behavior

Abstract

(1) Background: Preoptic region of hypothalamus is responsible to control maternal behavior, which was hypothesized to be associated with gene expressional changes. (2) Methods: Transcriptome sequencing was first applied in the preoptic region of rat dams in comparison to a control group of mothers whose pups were taken away immediately after parturition and did not exhibit caring behavior 10 days later. (3) Results: Differentially expressed genes were found and validated by quantitative RT-PCR, among them NACHT and WD repeat domain containing 1 (Nwd1) is known to control androgen receptor (AR) protein levels. The distribution of Nwd1 mRNA and AR was similar in the preoptic area. Therefore, we focused on this steroid hormone receptor and found its reduced protein level in rat dams. To establish the function of AR in maternal behavior, its antagonist was administered intracerebroventricularly into mother rats and increased pup-directed behavior of the animals. (4) Conclusions: AR levels are suppressed in the preoptic area of mothers possibly mediated by altered Nwd1 expression in order to allow sustained high-level care for the pups. Thus, our study first implicated the AR in the control of maternal behaviors.

Enhanced pup retrieval behaviour in a mouse model of polycystic ovary syndrome

“…With hyperandrogenism being a key feature in clinical PCOS and the basis for most preclinical animal models of the disorder, it is important to consider potential effects of elevated androgens on mammalian maternal behaviour. A recent RNA‐sequencing analysis of the MPOA of lactating rats with and without pups, showed that androgen receptor (AR) expression is downregulated in the presence of pups 65 . In that same study, central administration of an AR antagonist to rat dams increased pup‐directed behaviour, 65 suggesting that AR‐signalling in the brain suppresses normal postpartum maternal behaviour.…”

“…A recent RNA‐sequencing analysis of the MPOA of lactating rats with and without pups, showed that androgen receptor (AR) expression is downregulated in the presence of pups 65 . In that same study, central administration of an AR antagonist to rat dams increased pup‐directed behaviour, 65 suggesting that AR‐signalling in the brain suppresses normal postpartum maternal behaviour. To date, few studies have investigated the impact of androgen administration during pregnancy on subsequent maternal behaviour in mammals.…”

Medial preoptic circuits governing instinctive social behaviors

“… 88 In turn, AR levels were also suppressed in the MPOA of mothers. 89 In contrast, it has been observed that during parturition 90 , 91 and during lactation 92 there is an increase in OTR levels in mothers' MPOA. Furthermore, hormones can affect each other’s receptor levels, as evidenced by estrogen-induced progesterone receptor (PR) expression, 93 and progesterone’s ability to elevate prolactin receptor levels (PRLRs).…”