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Reprod Biol Endocrinol

Title:		Genipin improves reproductive health problems caused by circadian disruption in male mice
Author(s):		Xu Y; Wang L; Cao S; Hu R; Liu R; Hua K; Guo Z; Di HJ; Hu Z;
Address:		"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, 210023, Nanjing, China. Department of Endocrinology, The Second Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 210017, Nanjing, China. dihongjie@sina.com. Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, 210023, Nanjing, China. huzg_2000@126.com"
Journal Title:		Reprod Biol Endocrinol
Year:		2020
Volume:		20201211
Issue:		1
Page Number:		122 -
DOI:		10.1186/s12958-020-00679-9
ISSN/ISBN:		1477-7827 (Electronic) 1477-7827 (Linking)
Abstract:		"BACKGROUND: Circadian rhythm disruption impacts a wide range of physiological processes, including fertility. However, the effect of circadian disruption on male spermatogenesis and fertility, and treatments for these effects have been largely unexplored at the molecular level. METHODS: In this study, we examined the effects of genipin on improving the reproductive health problems caused by circadian disruption. Three groups of animals were fed under different conditions: control group (normal T cycle with saline), group of shortened T cycles (Light/Dark = 4 hours/4 hours) with saline, and a group of shortened T cycles with genipin by oral gavage. The male fertility was evaluated by fertility study and pups parameters analysis after successful sexual behavior and mating with female mice. We sacrificed the treated animals after 5 or 10 weeks and collected the testis, sperm and serum for histological analysis, sperm motility assay, and serum hormone detection, respectively. Furthermore, the effect of genipin was assessed by detection of progesterone secretion and steroidogenic key proteins expression, including StAR and CYP11A1, in mouse Leydig tumor MLTC-1 cells. RESULTS: Male mice exposed to shortened light-dark cycles, much shorter than 24 hours, had reduced fertility with decreased sperm concentrations and sperm motility. Male mice under circadian disruption have reduced testis size and abnormal morphology, leading to lower fertility rates, reduced litter size and pup body weight. Treatment with exogenous genipin, a natural plant-derived compound, alleviated circadian disruption-induced damage to fertility and spermatogenesis and normalized testosterone, dihydrotestosterone (DHT), and androstenedione (ASD) levels in the male mice. The levels of key proteins involved in steroidogenesis, StAR and CYP11A1, were reduced in mouse testes after the circadian disruption, but genipin treatment restored the reduction. The mRNA expression of SRD5A1, which encodes an androgen synthesis enzyme, was also upregulated by genipin treatment. Furthermore, genipin treatment showed a positive effect on steroidogenesis in MLTC-1 cells, resulting in an increase in hormone secretion and the upregulation of StAR and CYP11A1. CONCLUSIONS: Our results showed an association between circadian disruption and reproductive health problems in male mice and indicated that treatments with genipin have positive effects on the reproductive health of male mice with circadian rhythm disorders"
Keywords:		"3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics/metabolism Androstenedione/blood Animals Cell Line, Tumor Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism Circadian Rhythm/*physiology Dihydrotestosterone/blood Female Fertility/*drug effects/physi;"
Notes:		"MedlineXu, Yihua Wang, Li Cao, Siyuan Hu, Ruihua Liu, Rui Hua, Ke Guo, Zhigang Di, Hong-Jie Hu, Zhigang eng 31400659/National Natural Science Foundation of China/ 19KJA180010/Natural Science Fund of Colleges and Universities in Jiangsu Province/ England 2020/12/15 Reprod Biol Endocrinol. 2020 Dec 11; 18(1):122. doi: 10.1186/s12958-020-00679-9"