Genipin improves reproductive health problems caused by circadian disruption in male mice

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.

Silk sericin alleviates aberrant photoperiod-induced alterations in testicular and adrenal steroidogenesis in adult mice

“…An extract from Gardenia jasminoides Ellis, a genipin, reversed the adverse changes in spermatogenesis and fertility caused by photoperiod disturbance in male mice. A normalization of sex hormones and proteins involved in steroidogenesis was observed, as well as a reduction of atrophy of the seminiferous tubules, decreased vacuolization, and restoration of typical control animals' sperm motility and concentration [41].…”

“…Although it is known that the desynchronization of endogenous circadian clocks affect each level of the HPG axis, the level of sex hormones, the process of spermatogenesis, final sperm concentration and motility, and, ultimately, fertility -both in males of various vertebrate species and in humans [8,39,40]. It has been shown that mice exposed to shortened light-dark cycle (Light/ Dark = 4 hours/4 hours) for 5 or 10 weeks responded with reduced testes size, abnormal morphology, decreased sperm concentration and motility, and lowered levels of dihydrotestosterone and androstenedione [41]. In our experiment, we found that 5-week exposure to both SD and LD photoperiods reduced sperm count and motility and increased the number of abnormal sperm (Fig.…”

Novel Findings regarding the Bioactivity of the Natural Blue Pigment Genipin in Human Diseases

“…It also offers potential in biocatalyst design, particularly in food modifications [ 69 ]. The physicochemical characteristics of genipin-cross-linked hydrogels, as well as various information on the use of biomaterials for drug delivery, including ocular drug delivery, buccal drug delivery, anti-inflammatory drug delivery, oral drug delivery, are given in a recent review by Xu et al [ 70 ].…”