{"id":43248,"date":"2022-03-31T12:00:06","date_gmt":"2022-03-31T12:00:06","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=43248"},"modified":"2022-05-17T10:16:35","modified_gmt":"2022-05-17T10:16:35","slug":"chemosterilization-in-male-past-and-present-in-reproductive-biology","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol15no1\/chemosterilization-in-male-past-and-present-in-reproductive-biology\/","title":{"rendered":"Chemosterilization in Male: \u2018Past and Present\u2019 in Reproductive Biology"},"content":{"rendered":"

The effects of chemosterilizing agents on the testes and sperm production and maturation are much less understood than their effects on the ovaries and oogenesis. It\u00a0was discovered that sterilising male insects with ionising radiation caused the emergence of chromosome-wide or chromatid-specific dominant lethal mutations, which led to the\u00a0development of the classical male castration techniques1, 2<\/sup>. It was discovered in those investigations that alterations were not frequently found on spermatozoa, but that they\u00a0were commonly visible in anomalies during the division of the zygote in the fertilised egg2, 3<\/sup>. Dominant lethal mutation in the screw-worm, Cochliomyia hominivorax<\/em>, were first\u00a0discussed vividly by LaChance & Riemann (1964)3<\/sup> and LaChance & Crystal (1965)4<\/sup>, in the most classic experiments ever conducted. Detailed information on and complications\u00a0related to dominant lethal mutations in insects caused by irradiation and sterilizing agents have been enumerated by LaChance (1967), who has also incorporated a detailed references containing research that dispensed this arena long before the era when\u00a0chemosterilizing agents were introduced into the scientific community5<\/sup>.<\/p>\n

Chemical castration is no longer considered to be a real castration because it is no more invasive these days. When the treatment is stopped, it is generally considered to be reversible, but not always. It has been discovered in a number of recent experiments\u00a0that chemosterilization has the ability to reduce testosterone levels in the bloodstream6, 7<\/sup>. Endogenous androgens are important regulators of male sexuality7, 8<\/sup>. Testosterone levels have an effect on both erections and ejaculations9, 10<\/sup>. A testosterone surge, on the\u00a0other hand, occurs as a result of sexual activity11, 12<\/sup>. As a result, androgen receptor antagonists such as steroid antiandrogens and GnRH-agonists diminish sex drive by hindering androgen receptor binding13<\/sup>.<\/p>\n

As a result, both classical and recent experiments have demonstrated that chemosterilizing agents have an effect on the testicles and spermatogenesis14, 15<\/sup>. In present times, there lacks reasonable relevance of strong mutagens, such as those used\u00a0in conventional insect research, and recent research has looked into the possibility of using chemicals to cause aspermia or inactivate sperm for the purpose of sterilisation.<\/p>\n

The mechanism of action of these chemicals investigated thus far showed that spermatogonia and developing spermatocytes that are undergoing division are the most affected cells16, 17<\/sup>. As a result of the degeneration of spermatogenic cells, the size of the testicles as a whole decrease18<\/sup>. It is because they are androgen dependant that the\u00a0accessory glands degenerate and the sperm transport during copulation is prevented19<\/sup>. The results of recent animal experiments lend further support to this theory20<\/sup>. Recent studies have also demonstrated that some chemosterilizing agents are capable of inducing oxidative stress (i.e.,<\/em> generating reactive oxygen species) in the environment6, 21\u00a0<\/sup>Several other studies have reported that certain chemicals have steroidogenesis inhibitory activities18<\/sup>. Previous investigations on the induction of dominant lethal mutations have also stated that the impacts of chemosterilizing agents on sperm production and maturation are frequently followed by a decrease in the vitality of sperm,\u00a0which may result in its immobility or even death4, 5<\/sup>. The degree of spermatozoa motility in spermathecae of Musca domestica<\/em> (common housefly) females that had been sterilized with Brestan and Tinicide was investigated in another classic experiment conducted by Ascher et al.<\/em> (1968). In their research, they discovered that the extent of fertility is directly proportional to the degree of sperm motility20<\/sup>.<\/p>\n

So far, different chemosterilizing agents have been tested and found to be effective, but two of the most effective are medroxyprogesterone acetate (MPA) and cyproterone acetate (CA). It is also popular by the brand names Clinovir, Cycrin, Depo-Provera, and Hystron. MPA is a hormonal castration agent used for the treatment of male infertility. MPA was first introduced to the market in order to treat female gynaecological\u00a0issues. It has also been known for worsening drug therapy and the risk for the induction of non-alcoholic fatty liver disease (NAFLD)22, 23<\/sup>. Medicinal marijuana (MPA) was removed from the market by the Food and Drug Administration (FDA) in 1978. MPA is\u00a0available as a birth control pill in countries other than the United States; however, the FDA has never approved it for this purpose. For the first time, Heller et al.<\/em> (1958) discovered that progestational compounds reduced testicular volume and completely\u00a0suppressed male libido in males2<\/sup>4<\/sup>. MPA suppresses testosterone production by inhibiting gonadotropin secretion, which in turn suppresses testosterone production. MPA has been\u00a0shown to accelerate testosterone metabolism in the liver, resulting in lower testosterone levels in the blood25<\/sup>. MPA is administered as a 400 mg intramuscular injection once a\u00a0week, administered intravenously24, 25<\/sup>. The effects of MPA are noticeable within 2-3 weeks of beginning of the treatment. Gagne (1981) conducted a historical study with 48\u00a0respondents, finding that forty participants responded positively to MPA and that all participants experienced decreased sexual fantasy, arousal, and urges as a result\u00a0(particularly masturbation). MPA has been shown to significantly reduce the number of ejaculations and testosterone levels in the bloodstream26<\/sup>. As an alternative, cyproterone\u00a0acetate (CPA), which is marketed under the brand names Androcur, Cyprone, Cyprostat, and Dianette, is not formally permitted in the United States, but is approved in Canada,\u00a0the United Kingdom, and Germany for use in the treatment of acne. Because MPA and CPA are not available in the same countries, it is difficult to conduct comparative studies\u00a0between the two drugs. Laschet and Laschet (1971) conducted a study on the clinical uses of CPA in which they administered CPA at 100mg oral doses daily or 300mg\u00a0intramuscularly every two weeks to 100 sexually deviant male participants significantly reduced or eliminated sexual drive, erections, and orgasms. Competitive inhibition of\u00a0testosterone and DHT at androgen receptors is the mechanism by which CPA reduces testosterone production. CPA, like MPA, has a suppressive effect on sexual fantasies,\u00a0libido, the number of ejaculations, and spermatogenesis in the male reproductive system27<\/sup>.<\/p>\n

There is little information available about the behavioural consequences of chemocastration. However, only a few studies have been conducted in this area. Vinke\u00a0et al.<\/em> (2008) have reported the effects of surgical and chemocastration on inter-male aggression, sexual behaviour, and play behaviour in male ferrets (European polecats)\u00a0were assessed and compared in order to determine which was more effective. Animals that had undergone chemical castration showed less aggression toward other males,\u00a0regardless of whether or not they were in the presence of a receptive female. Chemical castration, as opposed to surgical castration, had a greater impact on the reduction of\u00a0aggression2<\/sup>8<\/sup>. In 2001, researchers conducted a study to establish the impacts of deslorelin administration on regulation of reproduction and sexual behaviour in wild\u00a0animals. The results were published in the journal Biological Control. However, despite the fact that this study was brief and only with a small number of animals, the subsequent\u00a0primary annotations were recorded: After being treated with a deslorelin implant, male sea otter antagonistic behaviour was no longer observed, and no adverse effects on\u00a0social behaviour were observed in four male cheetahs who were also treated with deslorelin29<\/sup>.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Marec F, Vreysen MJB. Advances and Challenges of Using the Sterile Insect Technique for the Management of Pest Lepidoptera. Insects<\/em>; 10(11):371 (2019).
    \nCrossRef<\/a><\/li>\n
  2. Robinson AS. Mutations and their use in insect control. Mut Res<\/em>; 511(2):113-32 (2002).
    \n    CrossRef<\/a><\/li>\n
  3. Lachance LE, Riemann JG. Cytogenetic investigations on radiation and chemically induced dominant lethal mutations in oocytes and sperm of the screw-worm fly. Mut Res<\/em>; 106:318-33 (1964).
    \n    CrossRef<\/a><\/li>\n
  4. Lachance LE, Crystal MM. Induction of dominant lethal mutations in insect oocytes and sperm by gamma rays and an alkylating agent: Dose-response and joint action studies. Genetics<\/em>; 51(5):699-708 (1965).
    \n    CrossRef<\/a><\/li>\n
  5. LaChance LE. The induction of dominant lethal mutations in insects by ionizing radiation and chemicals-as related to the sterile male technique of insect control. Genet Insect Vect Dis<\/em>; 21:617-50 (1967).<\/li>\n
  6. K. CA, Sengupta P, Goswami H, Sarkar M. Excessive dietary calcium in the disruption of structural and functional status of adult male reproductive system in rat with possible mechanism. Mol Cell Biochem<\/em>; 364(1-2):181-91 (2012).
    \n    CrossRef<\/a><\/li>\n
  7. Karmakar SN, Das SK. Chemosterilization induced by intratesticular injection of calcium chloride (Cacl2<\/sub>)-a tool for population control. Int J Pharm Chem Biol Sci<\/em>; 7(1) (2017).<\/li>\n
  8. Sengupta P, Dutta S. Hormones in male reproduction and fertility. Asian Pac J Reprod<\/em>; 8(5):187-8 (2019).
    \n    CrossRef<\/a><\/li>\n
  9. Rubinow DR, Schmidt PJ. Androgens, brain, and behavior. Am J Psych<\/em>; (1996).<\/li>\n
  10. Tahtali \u0130N. Is testosterone replacement an effective treatment of secondary premature ejaculation? Andrologia<\/em>; 52(1):e13452 (2020).
    \n    CrossRef<\/a><\/li>\n
  11. Jannini EA, Screponi E, Carosa E, Pepe M, Lo Giudice F, Trimarchi F, et al. Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone. Int J Androl<\/em>; 22(6):385-92 (1999).
    \n    CrossRef<\/a><\/li>\n
  12. Rastrelli G, Corona G, Maggi M. Testosterone and sexual function in men. Maturitas<\/em>; 112:46-52 (2018).
    \n    CrossRef<\/a><\/li>\n
  13. Hawley WR, Mosura DE. Effects of progesterone treatment during adulthood on consummatory and motivational aspects of sexual behavior in male rats. Behav Pharmacol<\/em>; 30(7):617-22 (2019).
    \n    CrossRef<\/a><\/li>\n
  14. LaChance LE, Degrugillier M, Leverich AP. Comparative effects of chemosterilants on spermatogenic stages in the house fly I. Induction of dominant lethal mutations in mature sperm and gonial cell death. Mut Res<\/em>; 7(1):63-74 (1969).
    \n    CrossRef<\/a><\/li>\n
  15. Lachance LE, Degrugillier M. Comparative effects of chemosterilants on spermatogenic stages in the house fly. II. Recovery of fertility and sperm transfer in successive matings after sterilization with 1, 3-propanediol dimethanesulfonate or X-rays. Ann Entomol Soc Am<\/em>; 63(2):422-8 (1970).
    \n    CrossRef<\/a><\/li>\n
  16. Sengupta P. Environmental and occupational exposure of metals and their role in male reproductive functions. Drug Chem Toxicol<\/em>; 36(3):353-68 (2013).
    \n    CrossRef<\/a><\/li>\n
  17. Mishra P, Banerjee S. Chromosome Aberrations Induced by TEPA-an alkylating Chemosterilant in Spermatocytes of Callosobruchus chinensis Linn.(Coleaptera, Bruchidae). Cytologia<\/em>; 52(3):499-506 (1987).
    \n    CrossRef<\/a><\/li>\n
  18. Chandra AK, Sengupta P, Goswami H, Sarkar M. Effects of dietary magnesium on testicular histology, steroidogenesis, spermatogenesis and oxidative stress markers in adult rats. Indian J Exp Biol<\/em>; 51(1):37-47 (2013).<\/li>\n
  19. Hamilton EW, Sutter GR. Chemosterilizing southern corn rootworm beetles with apholate. J Eco Entomol<\/em>; 62(6):1285-8 (1969).
    \n    CrossRef<\/a><\/li>\n
  20. Ascher K, Meisner J, Nissim S. The effect of fentins on the fertility of the male housefly. World Rev Pest Contr<\/em>; 7(2):84-96 (1968).<\/li>\n
  21. Pagseesing S, Yostawonkul J, Surassmo S, Boonrungsiman S, Namdee K, Khongkow M, et al. Formulation, physical, in vitro and ex vivo evaluation of nanomedicine-based chemosterilant for non-surgical castration of male animals. Theriogenology<\/em>; 108:167-75 (2018).
    \n    CrossRef<\/a><\/li>\n
  22. Zhang JW, Liu Y, Li W, Hao DC, Yang L. Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450 enzymes. Eur J Clin Pharmacol;<\/em> 62(7):497-502 (2006).
    \n    CrossRef<\/a><\/li>\n
  23. Savidou I, Deutsch M, Soultati AS, Koudouras D, Kafiri G, Dourakis SP. Hepatotoxicity induced by cyproterone acetate: a report of three cases. World J Gastroenterol;<\/em> 12(46):7551 (2006).
    \n    CrossRef<\/a><\/li>\n
  24. Heller CG, Laidlaw WM, Harvey HT, Nelson WO. Effects of progestational compounds on the reproductive processes of the human male. Ann NY Acad Sci<\/em>; 71(5):649-65 (1958).
    \n    CrossRef<\/a><\/li>\n
  25. Gijs L, Gooren L. Hormonal and psychopharmacological interventions in the treatment of paraphilias: An update. J Sex Res<\/em>; 33(4):273-90 (1996).
    \n    CrossRef<\/a><\/li>\n
  26. Gagne P. Treatment of sex offenders with medroxyprogesterone acetate. Am J Psych<\/em>;\u00a0 (1981).<\/li>\n
  27. Laschet U, Laschet L. Psychopharmacotherapy of sex offenders with cyproterone acetate. Pharmacopsychiatry<\/em>; 4(02):99-104 (1971).
    \n    CrossRef<\/a><\/li>\n
  28. Vinke CM, van Deijk R, Houx BB, Schoemaker NJ. The effects of surgical and chemical castration on intermale aggression, sexual behaviour and play behaviour in the male ferret (Mustela putorius furo). Appl Anim Behav Sci<\/em>; 115(1-2):104-21 (2008).
    \n    CrossRef<\/a><\/li>\n
  29. Bertschinger H, Asa C, Calle P, Long J, Bauman K, DeMatteo K, et al. Control of reproduction and sex related behaviour in exotic wild carnivores with the GnRH analogue deslorelin: preliminary observations. J Reprod Fertil Suppl<\/em>; 57:275-83 (2001).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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