Bile acids alter male fertility through G-protein-coupled bile acid receptor 1 signaling pathways in mice

[Lokzo]

Bile acids alter male fertility through G-protein-coupled bile acid receptor 1 signaling pathways in mice

Bile acids (BAs) are signaling molecules that are involved in many physiological functions, such as glucose and energy metabolism. These effects are mediated through activation of the nuclear and membrane receptors, farnesoid X receptor (FXR-a) and TGR5 (G-protein-coupled bile acid receptor 1; GPBAR1). Although both receptors are expressed within the testes, the potential effect of BAs on testis physiology and male fertility has not been explored thus far. Here, we demonstrate that mice fed a diet supplemented with cholic acid have reduced fertility subsequent to testicular defects. Initially, germ cell sloughing and rupture of the blood-testis barrier occur and are correlated with decreased protein accumulation of connexin-43 (Cx43) and N-cadherin, whereas at later stages, apoptosis of spermatids is observed. These abnormalities are associated with increased intratesticular BA levels in general and deoxycholic acid, a TGR5 agonist, in particular. We demonstrate here that Tgr5 is expressed within the germ cell lineage, where it represses Cx43 expression through regulation of the transcriptional repressor, T-box transcription factor 2 gene. Consistent with this finding, mice deficient for Tgr5 are protected against the deleterious testicular effects of BA exposure. Conclusions: These data identify the testis as a new target of BAs and emphasize TGR5 as a critical element in testicular pathophysiology. This work may open new perspectives on the potential effect of BAs on testis physiology during liver dysfunction


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[shine]

So what is the deal here? Does this mean that all bile acids are bad for fertility, or only deoxycholic acid? What about TUDCA or ox bile?

 

[Inaut]

So what is the deal here? Does this mean that all bile acids are bad for fertility, or only deoxycholic acid? What about TUDCA or ox bile?

Or taurine?

 

[shine]

Or taurine?

Taurine Increases Spermatozoa Quality and Function in Asthenospermia Rats Impaired by Ornidazole - PubMed

Asthenospermia has been considered as one of the crucial causes of male infertility, which was closely related to epididymal dysfunction. Lots of documents have revealed that taurine palys an important role in male reproduction, including antioxidation, membrane stabilization, stimulation of...

pubmed.ncbi.nlm.nih.gov

Taurine deficiency in sperm causes male infertility

Sperm cells have a unique shape that allows them to travel. During fertilization, sperm pass through several physiological environments while still maintaining their shape, using poorly understood mechanisms. Researchers found that male mice lacking cysteine dioxygenase, a protein involved in...

www.sciencedaily.com

 

[shine]

G protein-coupled bile acid receptor - Wikipedia

en.wikipedia.org

This page is about the TGR5 receptor that was talked about in the study @Lokzo posted.

"One effect of this receptor is to activate deiodinases which convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). T3 in turn activates the thyroid hormone receptor which increases metabolic rate."

So activation of TGR5 by bile acids leads to higher levels of T3 and metabolic rate yet lowers fertility. I don't know what to make of this.

 

[Korven]

So what is the deal here? Does this mean that all bile acids are bad for fertility, or only deoxycholic acid? What about TUDCA or ox bile?

I think the problem is when you have a sluggish liver and cholestasis (impaired bile flow) and toxic bile acids aren't getting pooped out but leak into the blood - similar to what happens during cholestasis of pregnancy:

"Total serum bile acid levels were markedly elevated in all patients and correlated with impaired fetal prognosis." The Importance of Serum Bile Acid Level Analysis and Treatment With Ursodeoxycholic Acid in Intrahepatic Cholestasis of Pregnancy

TUDCA seems to be a good guy as it gets the bile flowing in the right direction, whereas perhaps other bile acids like cholic/deoxycholic acid aren't so great taken as a supplement, especially if you're already dealing with liver and gallbladder issues or a gut microbiome issue (bacteria creating secondary bile acids).

Interestingly when I took TUDCA before it just made me really nauseous and I didn't feel like I got any benefits. A low fat diet and 4 pints of hot water per day has been the most effective thing I've done so far for keeping my gallbladder happy.

 

[Korven]

From the authors of the study:

"Finally, it is worth mentioning that several correlations exist in humans between liver diseases and altered male fertility.41,42 Given that many liver diseases are characterized by a severely impaired BA homeostasis, it is tempting to speculate that pathological BA levels in serum may initiate testicular alterations during the early stages of liver dysfunction and subsequently promote subfertility. In this context, plasma BA concentrations and pool composition may offer promising tools for early diagnosis of testicular subfertility in patients with liver diseases. Although more human studies are warranted to corroborate this correlation in humans, our mouse studies provide strong indications for a deleterious effect of chronic BA exposure on testicular pathophysiology and fertility disorders."