Male fish are generally heavier and grow faster than female fish. Therefore, in order to ensure the supply of fish meat to the greatest extent, people use sex control technology to increase the yield and variety of fish under the premise of ensuring that exogenous hormones are harmless to the human body.

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Special Issue：What hormones are typically used for fish
sex reversal?
1.Introduction of fish sex reversal........................................................................................2
2.What is the mechanism of fish sex reversal?....................................................................2
3.Why need to reverse fish sex?...........................................................................................4
4.How to reverse fish sex?................................................................................................... 5
5. What influenced the fish sex reversal?............................................................................ 6
(1) Gene.......................................................................................................................... 6
(2) Temperature............................................................................................................. 7
(3) Genous hormones.....................................................................................................7
6.What are the commonly used hormones for fish sex reversal?........................................8
(1) 17-Methyltestosterone powder?............................................................................. 8
(2) Letrozole powder......................................................................................................9

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7.Where to buy the 17-methyltestosterone and Letrozole?...............................................10
1.Introduction of fish sex reversal
Fish sex reversal means that fish can change their original sex under certain conditions,
from male to female, or from female to male, or have both sexes at the same time. The
mechanism and reason of sex reversal in fish are still not completely clear, and it may be
related to factors such as genetics, environment, and hormones. There are many species of
fish that have natural or artificially induced sex reversal, such as eels, groupers, snappers,
and tilapias. Fish sex reversal has certain significance for aquaculture and resource
protection. It can improve yield and quality, and can also increase genetic diversity and
adaptability.
2.What is the mechanism of fish sex reversal?
Fish realizes its reproductive function and determines its final phenotype by controlling the
development and differentiation of germ cells. In this process, hormone regulation is an
important link. Hormone regulation mainly includes two systems, the
hypothalamic-pituitary-gonadal axis (HPG axis) and the hypothalamic-pituitary-thyroid axis
(HPT axis).
The HPG axis refers to the secretion of gonadotropin-releasing factor (GnRH) by the
hypothalamus, which stimulates the secretion of gonadotropin (GTH) by the pituitary gland,
and then acts on the gonads to promote the synthesis and secretion of estrogen and

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hormones, as well as the proliferation and maturation of germ cells. Estrogen feedback
regulates the activity of hypothalamus and pituitary gland, forming a dynamic balance.
The HPT axis refers to the secretion of thyrotropin-releasing factor (TRH) by the
hypothalamus, which stimulates the secretion of thyroid-stimulating hormone (TSH) by the
pituitary gland, which in turn acts on the thyroid gland, promotes the synthesis and
secretion of thyroid hormones, and regulates systemic metabolism. Thyroid hormone
feedback regulates the activity of hypothalamus and pituitary gland, forming a dynamic
balance.
When fish encounter factors that induce sex reversal, the above two systems will change,
causing the original male-female balance to be broken, which will trigger a series of gene
expression, cell proliferation, tissue remodeling and other processes, and finally achieve sex
change.
(1) When a fish reverses from male to female, it may go through the following steps:

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①Degeneration of male characteristics: testis began to shrink, sperm production
decreased or stopped, testicular stromal cells decreased or disappeared, and testosterone
levels decreased.
②Induction of female characteristics: ovarian primordia begin to increase, oocytes begin
to proliferate or rejuvenate, ovarian stromal cells begin to appear or increase, and estradiol
levels increase.
③Stable female characteristics: fully developed ovaries, normal ovulation, ovulation cycle
establishment, stable estradiol levels, etc.
(2) When a fish reverses from female to male, it may go through several steps:
①Regression of female characteristics: ovaries begin to shrink, oocytes begin to decrease
or degenerate, ovarian stromal cells decrease or disappear, and estradiol levels decrease,
etc.
②Induction of male characteristics: testicular primordia begin to increase, spermatogonia
begin to proliferate or rejuvenate, testicular stromal cells begin to appear or increase, and
testosterone levels increase.
③Stable male characteristics: fully developed testes, normal sperm production, mating
behavior, stable testosterone levels, etc.
3.Why need to reverse fish sex?

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The purpose of fish sex change is mainly to maximize the reproduction of offspring and to
enable individuals to obtain the stimulation of the sex. And why among vertebrates, only
fish undergo sex change? Experts believe that the increasing differentiation among
individuals of higher vertebrates led to this phenomenon. Now science has proved that
exogenous hormones can also denature fish that cannot be denatured. Whether it is larvae
or adult fish, after proper treatment, monophyletic or primary monophyletic populations
can be obtained. Male fish are generally heavier and grow faster than female fish.
Therefore, in order to ensure the supply of fish meat to the greatest extent, people use sex
control technology to increase the yield and variety of fish under the premise of ensuring
that exogenous hormones are harmless to the human body.
4.How to reverse fish sex?
The main means to achieve fish sex reversal are as follows:
Exogenous hormone induction: By injecting or implanting male or female hormones into
fish, the gonads of fish will change, thereby changing their sex. This method can artificially
control the sex ratio and reproductive cycle of fish and improve the efficiency of
farming.The common exogenous hormones are 17-Methyltestosterone and Letrozole.
Influence of environmental factors: By changing the temperature, light, density, nutrition
and other conditions of fish life, it affects the hormone level and gene expression in the fish,
thereby inducing its sex reversal. This method is more natural, but less controllable and
predictable.

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Gene manipulation: by editing or transferring the chromosomes or genes of fish, making
them have specific sex-determining genes or missing some key genes, so as to realize their
sex reversal. This approach can create new strains and traits, but is technically difficult and
may have safety and ethical concerns.
5.What influenced the fish sex reversal?
(1) Gene
The genetic sex determination mechanism means that the sex differentiation direction of
animals is not affected by external environmental factors, and is determined by the genetic
genes on the sex chromosomes. The sex-determining gene itself does not participate in the
differentiation of sex, but can only control its “determination process” and initiate a series
of sex differentiation events. The genetic sex determination process is a series of complex

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biochemical processes interacting, which ultimately lead to the determination and
differentiation of sex cells. Some components or combinations of components in the
pathway may become the dominant factors affecting the direction of sex determination.
(2) Temperature
During the hatching process of fish eggs, there will be a special period called the
temperature sensitive period (temperature sensitive period, TSP). During the temperature
sensitive period, artificially raising or lowering the temperature can ignore the influence of
genetic factors to change the direction of sex differentiation and sex ratio. There are even
gender reversals. For example, Nile tilapia enters a temperature-sensitive period 9 days
after fertilization. During this period, a certain proportion of hereditary females will revert
to physiological males if treated at a high temperature of 36°C. VASA immunohistochemical
staining showed that the gonads of Nile tilapia treated with high temperature changed
from ovarian type to testicular type at 21-39 days after fertilization; the gonads of
hereditary females treated with high temperature at 99 days after fertilization changed into
true testes.
(3) Genous hormones
Fish sex has strong plasticity, and artificially changing the external environment can also
reverse the sex of fish phenotype. There are two main methods of artificially inducing sex
reversal in fish, one is adding exogenous hormones to directly change hormone levels to
induce sex reversal. Common drugs include 17-methyltestosterone ((17-MT),

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11-ketotestosterone (11-KT), 17-estradiol (E2), etc.The second is to add inhibitor drugs to
interfere with hormones and receptors in the body in combination, reduce the level of fish
sex hormones, such as aromatase inhibitors and so on.
6.What are the commonly used hormones for fish sex reversal?
(1) 17-Methyltestosterone powder?
 What is 17-Methyltestosterone powder？
17-Methyltestosterone also known as 17-alpha-Methyltestosterone, 17a-MT, methyltest or
as 17α-methylandrost-4-en-17β-ol-3-one, is a synthetic, orally active androgenic-anabolic
steroid (AAS) and 17α-methylated derivative of testosterone that is used to treat males with
androgen deficiency. It bears close structural similarity to testosterone, but has a methyl
group at the C17α position in order to increase oral bioavailability. Due to efficient
aromatization into the potent estrogen methylestradiol, 17-Methyltestosterone Powder has
relatively high estrogenicity and hence potential side effects such as gynecomastia.
 What is 17-Methyltestosterone powder used for?
①Medical use: 17 alpha- Methyltestosterone Powder is or has been used in the treatment
of delayed puberty, hypogonadism, cryptorchidism, and erectile dysfunction in males, and
in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and
to increase libido and energy), postpartum breast pain and engorgement, and breast cancer
in women.
②Non-medical use: Methyltestosterone Powder is used for physique and
performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters,
although it is not commonly used relative to other AAS for such purposes.

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③Aquaculture use: MT ( 17α-Methyltestosterone) is a commonly used exogenous
androgen. Studies have shown that 100% male rate can be obtained by using 50 ug/g MT to
treat female Oreochromis niloticus; using 400 ug/ml of MT to treat hatching Oncorhynchus
tshawytscha can get 100% male rate;fertilized Cyprinus carpio were treated with 5 ug/ml of
MT soaking method for 75 hours and then fed with 50 mg/kg of MT every day for 40 to 70
days, and 100% male offspring could be obtained.
(2) Letrozole powder
 What is Letrozole powder?
Letrozole Powder is an anti-estrogen and one of the most potent Aromatase Inhibitor. It is
commonly sold under the brand name Femara among others. Now It is used by many
bodybuilders during post cycle therapy (PCT) and complements other anabolic steroids or
prohormones. Letrozole Powder helps the body get back to its normal stage and stabilize
the hormonal levels.
 What is Letrozole powder used for?

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①Treating breast cancer: Letrozole Powder is a medicine used for treating breast cancer. It
can also help prevent breast cancer coming back.It is mainly prescribed for women who
have been through the menopause and have a type of cancer called “hormone-dependent”
breast cancer.
②Induce and Increase Ovulation: Letrozole Powder encourages the ovaries to ovulate by
producing more natural stimulation. Femara Powder improves ovulation by blocking
estrogen production, which causes the body to release higher than normal levels of
follicle-stimulating hormone (FSH). The additional levels of FSH stimulate ovarian follicle(s)
to develop and mature in the ovary. For women who don’t ovulate regularly or who have
Polycystic Ovarian Syndrome (PCOS), the increased amounts of FSH can help to produce
mature follicle(s) and egg(s), so ovulation can occur.
③Achieving fish sex reversal: Studies have shown that aromatase is a key enzyme involved
in the regulation of fish sex differentiation, and the sex determination of fish can be
changed by regulating the expression of aromatase. Aromatase inhibitors (AI) can reduce
the activity of aromatase, block the pathway of testosterone and other male hormones into
estrogens, and change the ratio of male hormones to estrogens in the body, thereby
inducing masculinization of fish. Letrozole (LZ) is a commonly used aromatase inhibitor,
which can achieve sex control of fish by inhibiting aromatase activity, and has important
application value in aquaculture.
7.Where to buy the 17-methyltestosterone and Letrozole?
17-Methyltestosterone and letrozole can be sold in different forms, for example, raw
materials, tablets, pills, etc. Currently, there are many manufacturers and suppliers

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supplying 17-methyltestosterone and Letrozole, but the 17-methyltestosterone and
letrozole they sell are in different forms. Here are some information of the manufacturer
and supplier of 17-Methyltestosterone and letrozole for your reference.
①AdvaCare: a different kind of pharmaceutical and healthcare products company. AdvaCare
can provide 17-Alpha-Methyltestosterone and Letrozole tablets. The dose of MT is 5 mg, and
the specification is 10 tablets per box; the dose of letrozole is 2.5 mg, and the specification is 10
tablets per box.
③Kabir Life Sciences: a well-known platform for obtaining high-quality pharmaceutical
products through a variety of services, such as pharmaceutical manufacturing, PCD
franchise, and exporting their products internationally. They can provide
17-Methyltestosterone and Letrozole in tablets, the exact specifications can be found on the
order.
*Precaution: It is important to note that the use and sale of these substances is heavily
regulated, and obtaining them without a valid prescription is illegal and potentially
dangerous. Individuals seeking to use 17-methyltestosterone and letrozole for medical
purposes should consult a licensed healthcare professional who can provide guidance on
the appropriate use and sources of these drugs. It is important to follow all safety and legal
guidelines to avoid potentially harmful consequences.

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【Reference】
[1] Li SJ, Zhang YJ, Chai XS, Nie MF, Zhou YY, Chen JL, et al. Letrozole Ovulation Induction: An
Effective Option in Endometrial Preparation for Frozen-Thawed Embryo Transfer. Arch
Gynecol Obstetrics (2014) 289:687–93. doi: 10.1007/s00404-013-3044-0
[2] Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, et al. Androgen Receptor
Gene Expression in the Primate Ovary: Cellular Localization, Regulation, and Functional
Correlations. J Clin Endocrinol Metab (1998) 83:2479–85. doi: 10.1210/jcem.83.7.4917
[3] Cytogenetic toxicity and gonadal effects of 17 α-methyltestosterone in Astyanax
bimaculatus (Characidae) and Oreochromis niloticus (Cichlidae).
Rivero-Wendt CL, Miranda-Vilela AL, Ferreira MF, Borges AM, Grisolia CK.
Genet Mol Res. 2013 Sep 23;12(3):3862-70. doi: 10.4238/2013.September.23.4.
PMID: 24085447
[4] Franks S, Adams J, Mason H, Polson D. Ovulatory Disorders in Women With Polycystic
Ovary Syndrome. Clin Obstet Gynaecol (1985) 12:605–32. doi:
10.1016/S0306-3356(21)00138-2

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[5] Lack of genotoxicity in Astyanax bimaculatus and Oreochromis niloticus of
17α-methyltestosterone used in fish hatcheries to produce male monosex
populations.Rivero-Wendt CL, Miranda-Vilela AL, Ferreira MF, Amorim FS, da Silva VA,
Louvandini H, Grisolia CK. Genet Mol Res. 2013 Oct 24;12(4):5013-22. doi:
10.4238/2013.October.24.14. PMID: 24301763