Butyric acid regulates progesterone and estradiol secretion via cAMP signaling pathway in porcine granulosa cells

Abstract

Butyric acid (BA), one of the short chain fatty acids (SCFAs), has positive actions on the metabolism, inflammation, etc. However, whether it influences the reproductive physiology and if so the detail mechanism involved has not yet been determined. In this study, the porcine granulosa cells (PGCs) were treated with gradient concentrations of BA. After 24h culture, 0.05mM BA significantly stimulated the progesterone (P) secretion (P<0.05), 5mM and 10mM BA significantly inhibited the P secretion (P<0.05). Simultaneously, BA up-regulated the estradiol (E) secretion in a dose dependent manner, 5mM and 10mM BA significantly promoted the E level (P<0.05). In addition, 10mM BA significantly promoted the G-protein-coupled receptor 41/43 mRNA (P<0.05). Interestingly, 5mM BA treatment significantly down-regulated cyclic adenosine monophosphate (cAMP) content (P<0.05), steroidogenic acute regulatory (StAR), steroidogenic factor 1 (SF1), P450scc in the mRNA and/or protein level (P<0.05), and these actions were reversed by cAMP activator forskolin (FK). Moreover, the co-treatment of 5mM BA and bupivacaine (BPC, the cAMP inhibitor) significantly accumulated the inhibition action of BPC on cAMP, the secretion of P, and the abundance of StAR mRNA (P<0.05), inhibited the up-regulation of 5mM BA on the E secretion (P<0.05). Further, the Global Proteome and KEGG pathway analysis found that 5mM BA significantly up-regulated the I3LM80 proteins (P<0.05), which is involved in the steroid biosynthesis signaling pathway. 5mM BA significantly decreased the F2Z5G3 protein level (P<0.05), and the cAMP signaling pathway. In conclusion, present findings for the first time demonstrated that BA could regulate the P and E hormone synthesis in PGCs via the cAMP signaling pathway.

Di‐(2‐ethylhexyl) phthalate exposure induces female reproductive toxicity and alters the intestinal microbiota community structure and fecal metabolite profile in mice

“…90 The SCFA not only regulates the estradiol secretion but also participates in endogenous estrogen receptor-alpha-mediated signaling. 91,92 These result implied that the SCFAs potentially play an important role in DEHP-induced female reproductive toxicology. Overall, the reduction in the SCFA levels after DEHP exposure may be due to gut bacterial dysbiosis and alterations in gut permeability.…”

“…A study showed the changes of fecal microbiota composition and metabolites are related to the plasma reproductive hormones during pregnant and lactating stages in Bama mini pigs model 90 . The SCFA not only regulates the estradiol secretion but also participates in endogenous estrogen receptor‐alpha‐mediated signaling 91,92 . These result implied that the SCFAs potentially play an important role in DEHP‐induced female reproductive toxicology.…”

Effects of Diethyl Phosphate, a Non-Specific Metabolite of Organophosphorus Pesticides, on Serum Lipid, Hormones, Inflammation, and Gut Microbiota

“…The alteration of gut microbiota, as well as their metabolites, such as short-chain fatty acids (SCFAs), has been reported to play a role in the regulation of the testis‒pituitary axis [63] by disrupting steroid hormone synthesis [64]. It has been verified in cells that butyrate acid may increase the level of estradiol [65]. Accordingly, several butyrate-producing genera were significantly enriched in the DEP-H group, including Alloprevotella [66] and Intestinimonas [67] (Figure 5C, p < 0.05).…”

Butyrate drives the acetylation of histone H3K9 to activate steroidogenesis through PPARγ and PGC1α pathways in ovarian granulosa cells

“…Moreover, we found that butyrate can suppress early embryo loss through improving phospholipid metabolism and enhancing ovarian progesterone synthesis 12 . In vitro cultured granulosa cells of rats and pigs also suggest the improvements of progesterone and estradiol synthesis by butyrate 10,12 . However, the underlying molecular mechanism for this improvement is largely unknown.…”

“…SR‐BI/CD36 drives the transport of extracellular cholesterol into mitochondria for steroidogenesis 9 . In clinical practice, dietary fats have been reported to influence the levels of steroid hormones, including progesterone, estradiol, and testosterone, in mammals and rodents 10‐12 . We and others have found that maternal dietary butyrate supply during pregnancy leads to improvement of litter size and embryo implantation in rats 12,13 .…”