I was a little surprised to see this hasn’t been documented here.
Vitamin A1-deprived but all-trans-retinoic acid-supplemented male rats exhibit hypogonadism and infertility due to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due to fetal resorption caused by a lack of local retinoic acid synthesis in the embryo.[10][11] The retinoic acid synthesis in testes is catalyzed primarily by the RALDH2 (ALDH1A2) aldehyde dehydrogenase. Suppressing this enzyme has been proposed as a possible way to make a male contraceptive pill, because retinoic acid is necessary for spermatogenesis in humans, much as in rats.[
Go tell that to the “all vitamin A is poison” folks. It’ll go down real well.
There was something I posted on here long ago showing that a (very) small amount of 13-cis RA (Accutane) local to the testes was necessary to maintain sperm production.
Yup, accutane is naturally produced in small amounts, as a metabolite of Vit A. It’s needed for some biological functions. Like all things that are “needed”, too much or too little and you have a problem.
Here is a more recent study. Alot of good info here.
Coming from Accutane, the game we play where everything is mediated by androgens or the androgen receptor, you could also play that game with Retinoic Acid and its receptors.
Its involvement with skin and hair health, skin barrier function, gastrointestinal health, immunity, growth and development are all very well documented.
In fact I recently posted a study where a retinoic acid related receptor was actually working upstream of the androgen receptor and affected its function.
Just some things to keep in mind.
Retinoic acid receptor signaling is necessary in steroidogenic cells for normal spermatogenesis and epididymal function
Spermatogenesis in mammals is a very complex, highly organized process, regulated in part by testosterone and retinoic acid (RA). Much is known about how RA and testosterone signaling pathways independently regulate this process, but there is almost no information regarding whether these two signaling pathways directly interact and whether RA is crucial for steroidogenic cell function. This study uses a transgenic mouse line that expresses a dominant-negative form of RA receptor α (RAR-DN) and the steroidogenic cell-specific Cre mouse line, Cyp17 iCre, to generate male mice with steroidogenic cells unable to perform RA signaling. Testes of mutant mice displayed increased apoptosis of pachytene spermatocytes, an increased number of macrophages in the interstitium and a loss of advanced germ cells. Additionally, blocking RA signaling in Leydig cells resulted in increased permeability of the blood-testis barrier, decreased levels of the steroidogenic enzyme cytochrome P450 17a1 and decreased testosterone levels. Surprisingly, the epididymides of the mutant mice also displayed an abnormal phenotype. This study demonstrates that RA signaling is required in steroidogenic cells for their normal function and, thus, for male fertility.
On top of RAR having multiple affects on multiple biological processes. Accutane also induces p53/foxo1 which causes a downstream effect of reducing igf1,androgen receptor expression, dht, 5ar, and testosterone/mtorc1 mrna/expression. So not only are we dealing with hundreds of DIRECT (rar is involved in almost every biological process) effects from retonoic acid receptor activation, we are also dealing with repressed androgen signaling/androgen receptor function. The more I research the more hopeless I become. We are literally altered on a biological/genetic level…the fine tuning that’d be required to set us straight seems astronomically high.
@Calcified, I would guess it’s the difference between having an adequate concentration of either ATRA or 13-cis RA to maintain their desired effect, and the “controlled vitamin A poisoning” we went through.
Shared some relevant info about it here with a nice arm-chair theory to go along with it:
Simply put; for many things, there is an optimal range, and once that is exceeded, it may induce an opposite effect.
Doesn’t 20mg twice daily for 20 weeks in a study for fertility seem excessive, I get they were deficient, but I think that’s still fairly high, but it’s one of my favourite studies as it shows 13cis drop after treatment. It’s called isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia
There is one thought on this.
The inability to efficiently transform dietary vitamin a (including supplements) to retinoic acid.
Imagine never needing Accutane to begin with.
So here could be a scenario where there could be a build up of the storage form of vitamin a, while at the same time lacking the retinoic acid that is most involved in the biological functions of vitamin a.
Just to put that scenario out there.
@guitarman01 if there is an inability to transform to retinoic acid wouldn’t it result in high retinol levels? But it doesn’t seem to. Unless it’s all in ester form in liver or maybe usage in the skin is now massive?
This would be the extreme version of the what if scenario. There would likely be lesser versions of this.
Im sure it wouldn’t be a complete inability to convert vitamin a.
Hypothetically, the storage form though would accumulate in the liver first before spilling out into the bloodstream. (Keep in mind the majority are not having liver problems showing up on tests, even 20 years later)
I suppose im talking about a optimal level of retinoic acid as it benefits health, which would be endogenously sourced.
You could also wonder if taking Accutane could hurt the body’s ability to naturally generate retinoic acid or shut off production (sound familiar?), but thats starting to guess a little too much.
Isn’t it strange that doctors or scientists never show up here with thoughts and opinions on this? Or at least to learn. I wonder if they read this stuff?
Some of the things people have been diagnosed with seem questionable.
Im somewhat convinced on the foxo1/p53 theory. Foxo1 downregulates AR, DHT, IGF1, TESTOSTERONE, MTOR…you name it. It’s also (mostly) responsible for the muscle catabolism seen during chemotherapy . Foxo1 knockout mice show substantially reduced anxiety. One of my main accutane symptoms was an inability to gain muscle…this persisted for about 1.25 years. Milk, Insulin, BCAAS (in particular leucine) downregulate foxo1 and upregulate mtor1
