Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice

Enduring sex-dependent implications of pubertal stress on the gut-brain axis and mental health

“…The HPA axis, known as the stress response system, also undergoes maturation during puberty ( Smith et al, 2021 ). When encountered with a stressor, the HPA axis becomes activated, which initiates the stimulation and release of corticotropin-releasing hormone in the paraventricular nucleus of the hypothalamus ( Herman et al, 2016 ).…”

Testis–Gut-Reproduction Axis: The Key to Reproductive Health

“…Probiotics can produce SCFAs, protect intestinal barrier function, promote the production of anti-inflammatory factors such as interleukin 10 (IL-10), and inhibit the chronic low-grade inflammatory state [20,106]. Poutahidis et al [107] demonstrated that elderly mice fed with L. reuteri showed an increase in testicular interstitial area and a number of interstitial cells, an increase in nuclear volume, and an increase in serum T levels compared with the control group, indicating that probiotics restored Leydig cell function. At the same time, the study showed that this effect was achieved by inhibiting pro-inflammatory factor interleukin 17 (IL-17) and upregulating anti-inflammatory factor IL-10 [107].…”

“…Poutahidis et al [107] demonstrated that elderly mice fed with L. reuteri showed an increase in testicular interstitial area and a number of interstitial cells, an increase in nuclear volume, and an increase in serum T levels compared with the control group, indicating that probiotics restored Leydig cell function. At the same time, the study showed that this effect was achieved by inhibiting pro-inflammatory factor interleukin 17 (IL-17) and upregulating anti-inflammatory factor IL-10 [107]. Substances such as SCFAs and LPS derived from GM can directly act on the testes or affect the inflammatory state, thereby impacting the synthesis of androgens in the testes.…”

“…The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which promotes the synthesis and secretion of LH in the anterior pituitary gland and stimulates the synthesis of T by Leydig cells. LPS can restrain hypothalamic-pituitary function and reduce serum LH levels through mediators such as Kisspeptin, inflammatory factors, and hypothalamic-pituitary-adrenal axis [107,108]. However, Shen et al [109] suggest that intraperitoneal injection of LPS into adult male mice can lead to acute systemic inflammation, eventuating excessive activation of GnRH neurons in the medial preoptic area of the hypothalamus, ultimately increasing serum LH levels.…”

Immune signaling as a node of interaction between systems that sex-specifically develop during puberty and adolescence

“…The effects of inflammation on reproduction via GnRH and LH secretion occur through various mechanisms ( Wu and Wolfe, 2012 ). LPS-induced inflammation suppresses the HPG axis by inhibiting GnRH and LH pulsatile secretion and disturbing the ovarian response to gonadotropin stimulation ( Lee et al, 2019 , Smith et al, 2021 ). IL-1β is the most effective modulator of GnRH and subsequent LH secretion ( Barabas et al, 2020 , Kalra et al, 1998 ).…”