In:
Journal of Endocrinology, Bioscientifica, Vol. 248, No. 3 ( 2021-03), p. 337-354
Abstract:
Obesity is strongly linked to male infertility. Apoptotic inflammatory response caused by oxidative stress in testicular spermatogenic cells is one of the important causes of obesity-related male infertility. As bioactive peptide is secreted by the pituitary gland, pituitary adenylate cyclase activating polypeptide (PACAP) has a powerful triple role of anti-oxidation, anti-apoptosis, and anti-inflammation, and it is involved in the male reproduction regulation, but the specific mechanism remains unknown. The purpose of this study is to explore the role of PACAP in obesity-related male infertility. In cellular level experiments, mouse spermatocytes (GC-2) were treated with palmitate (PA) to establish an high-fat injury cell model in vitro and then treated with PACAP. In animal-level experiments, C57BL/6 male mice were fed with a high-fat diet (HFD) to induce obesity and subsequently treated with PACAP. The cell mechanism studies show that PACAP selectively binded to the PAC1 receptor to attenuate palmitic acid-induced mouse spermatogenic cell (GC-2) oxidative damage and apoptotic inflammatory response via the PKA/ERK/Nrf2 signaling axis. However, this mechanism was inhibited in GC-2 cells inhibiting the activity of Nrf2. The animal experiment studies show that PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes/body weight, serum lipids levels, and reproductive hormone levels in vivo . Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology and sperm parameters via Keap1/Nrf2/ARE pathway. These beneficial effects of PACAP were abolished in obese mice with testes-specific knockdown of Nrf2. Our data suggested that PACAP could ameliorate fertility in obese male mice and may be a promising candidate drug for obesity-induced male infertility.
Type of Medium:
Online Resource
ISSN:
0022-0795
,
1479-6805
Language:
Unknown
Publisher:
Bioscientifica
Publication Date:
2021
detail.hit.zdb_id:
1474892-7
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