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'''Sex reversal''' is a biological process whereby the pathway directed towards the already determined-sex fate is flipped towards the opposite sex, creating a discordance between the primary sex fate and the sex phenotype expressed.<ref name="Weber_2018">{{cite journal | vauthors = Weber C, Capel B | title = Sex reversal | language = en | journal = Current Biology | volume = 28 | issue = 21 | pages = R1234–R1236 | date = November 2018 | pmid = 30399341 | pmc = 8941919 | doi = 10.1016/j.cub.2018.09.043 | pmcdoi-access = 8941919free | doi-accessbibcode = free2018CBio...28R1234W }}</ref><ref>{{cite journal | vauthors = Charnov EL, Bull J | title = When is sex environmentally determined? | journal = Nature | volume = 266 | issue = 5605 | pages = 828–30828–830 | date = April 1977 | pmid = 865602 | doi = 10.1038/266828a0 | bibcode = 1977Natur.266..828C | s2cid = 4166753 | urlbibcode = https://digitalrepository1977Natur.unm266.edu/cgi/viewcontent.cgi?article=1010&context=biol_fsp828C }}</ref> The process of sex reversal occurs during embryonic development or before gonad differentiation. In [[Sex-determination system|GSD]] species, sex reversal means that the sexual phenotype is discordant with the genetic/chromosomal sex. In [[Temperature-dependent sex determination|TSD]] species, sex reversal means that the temperature/conditions that usually trigger the differentiation towards one sexual phenotype are producing the opposite sexual phenotype.<ref name="Weber_2018" />
 
Sex reversal can occur naturally, by mutations, or can be induced artificially. Sex reversal can be genetically or hormonally induced in laboratory. It can also occur artificially by exposure to endocrine disruptors such as [[pollutant]]s, including [[herbicide]]s, which can act as estrogen promoters or inhibitors, for instance by altering [[aromatase]] expression.<ref name="Gilbert_2010">{{cite book |last1=Gilbert |first1vauthors =Scott FGilbert | name-list-style = vancSF |url=https://books.google.com/books?id=aLzVQwAACAAJ|title=Developmental Biology|date=2010-04-15|publisher=Sinauer Associates |isbn=978-0-87893-384-6}}</ref><ref>{{cite journal | vauthors = Nakamura M | title = The mechanism of sex determination in vertebrates-are sex steroids the key-factor? | journal = Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology | volume = 313 | issue = 7 | pages = 381–98381–398 | date = August 2010 | pmid = 20623803 | doi = 10.1002/jez.616 | bibcode = 2010JEZA..313..381N }}</ref><ref>{{cite journal | vauthors = Chew KY, Renfree MB | title = Inducing Sex Reversal in Marsupial Mammals | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 301–312 | date = 2016 | pmid = 27794571 | doi = 10.1159/000450927 | s2cid = 749166 }}</ref><ref>{{cite journal | vauthors = Chan ST | title = Natural sex reversal in vertebrates | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 259 | issue = 828 | pages = 59–71 | date = August 1970 | pmid = 4399069 | doi = 10.1098/rstb.1970.0046 | doi-access = | bibcode = 1970RSPTB.259...59C | doi-access = free }}</ref>
 
== In vertebratesfishes ==
'''Gonochoristic Fishes'''
 
In gonochoristic fishes, the sex can be determined genetically, environmentally or by a combination of both. In fishes, primary sexual fate can be susceptible to alteration by hormones exposure and multiple environmental factors, such as population density, water pH, or temperature. Those conditions can affect the gonad development and differentiation, which can lead to sex reversal.<ref>{{cite journal | vauthors = Yamaguchi T, Kitano T | title = High temperature induces cyp26b1 mRNA expression and delays meiotic initiation of germ cells by increasing cortisol levels during gonadal sex differentiation in Japanese flounder | journal = Biochemical and Biophysical Research Communications | volume = 419 | issue = 2 | pages = 287–92287–292 | date = March 2012 | pmid = 22342721 | doi = 10.1016/j.bbrc.2012.02.012 }}</ref><ref>{{cite journal | vauthors = Baroiller JF, D'Cotta H | title = The Reversible Sex of Gonochoristic Fish: Insights and Consequences | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 242–266 | date = 2016 | pmid = 27907925 | doi = 10.1159/000452362 | doi-access = free }}</ref> In medaka fish, where sex reversal has been documented show a shared gene related to normal male development, the ''dmy'' gene. In wild populations, genetically female fate can be phenotypically reversed to males if they carry the ''dmy'' gene or a mutated ''dmy'' gene and genetic males can be reversed to females if they lack the ''dmy'' gene.<ref>{{cite journal | vauthors = Matsuda M, Shinomiya A, Kinoshita M, Suzuki A, Kobayashi T, Paul-Prasanth B, Lau EL, Hamaguchi S, Sakaizumi M, Nagahama Y | display-authors = 6 | title = DMY gene induces male development in genetically female (XX) medaka fish | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 10 | pages = 3865–703865–3870 | date = March 2007 | pmid = 17360444 | pmc = 1820675 | doi = 10.1073/pnas.0611707104 | doi-access = free | bibcode = 2007PNAS..104.3865M | doi-access = free }}</ref>
=== In gonochoristic fishes ===
In gonochoristic fishes, the sex can be determined genetically, environmentally or by a combination of both. In fishes, primary sexual fate can be susceptible to alteration by hormones exposure and multiple environmental factors, such as population density, water pH, or temperature. Those conditions can affect the gonad development and differentiation, which can lead to sex reversal.<ref>{{cite journal | vauthors = Yamaguchi T, Kitano T | title = High temperature induces cyp26b1 mRNA expression and delays meiotic initiation of germ cells by increasing cortisol levels during gonadal sex differentiation in Japanese flounder | journal = Biochemical and Biophysical Research Communications | volume = 419 | issue = 2 | pages = 287–92 | date = March 2012 | pmid = 22342721 | doi = 10.1016/j.bbrc.2012.02.012 }}</ref><ref>{{cite journal | vauthors = Baroiller JF, D'Cotta H | title = The Reversible Sex of Gonochoristic Fish: Insights and Consequences | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 242–266 | date = 2016 | pmid = 27907925 | doi = 10.1159/000452362 | doi-access = free }}</ref> In medaka fish, where sex reversal has been documented show a shared gene related to normal male development, the ''dmy'' gene. In wild populations, genetically female fate can be phenotypically reversed to males if they carry the ''dmy'' gene or a mutated ''dmy'' gene and genetic males can be reversed to females if they lack the ''dmy'' gene.<ref>{{cite journal | vauthors = Matsuda M, Shinomiya A, Kinoshita M, Suzuki A, Kobayashi T, Paul-Prasanth B, Lau EL, Hamaguchi S, Sakaizumi M, Nagahama Y | display-authors = 6 | title = DMY gene induces male development in genetically female (XX) medaka fish | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 10 | pages = 3865–70 | date = March 2007 | pmid = 17360444 | pmc = 1820675 | doi = 10.1073/pnas.0611707104 | bibcode = 2007PNAS..104.3865M | doi-access = free }}</ref>
 
'''Hermaphroditic Fish'''
==== Induced reversal in aquaculture industry ====
 
Within seven [[teleost]] fish families, two modes of [[Hermaphrodite|hermaphrodism]] can be observed—simultaneous hermaphrodism and sequential hermaphrodism. These cases often arise due to social factors, such as a decline in population or changes in dominance. <ref name=":2">{{cite journal | vauthors = Sunobe T, Sado T, Hagiwara K, Manabe H, Suzuki T, Kobayashi Y, Sakurai M, Dewa SI, Matsuoka M, Shinomiya A, Fukuda K, Miya M | title = Evolution of bidirectional sex change and gonochorism in fishes of the gobiid genera Trimma, Priolepis, and Trimmatom | journal = Die Naturwissenschaften | volume = 104 | issue = 3–4 | pages = 15 | date = April 2017 | pmid = 28251305 | pmc = 5332495 | doi = 10.1007/s00114-017-1434-z | bibcode = 2017SciNa.104...15S }}</ref> It is assumed that hermaphroditic sex changing fish have increased plasticity within their gonads compared to the typical gonochoristic fish, allowing for gonadal differentiation. Although it is not a reversal of sex, simultaneous hermaphrodism is beneficial for low-density populations as it allows for an increase in conspecific mating opportunities overall. Simultaneous hermaphrodism occurs when fish are able to produce both mature sperm and eggs within their gonads—while self-fertilization is rare, it has been seen to occur in few low-density populations such as the ''Kryptolebias marmoratus.''<ref>{{cite book | vauthors = Sawada K | chapter = Simultaneous Hermaphroditism in Fishes |date=2023 | veditors = Kuwamura T, Sawada K, Sunobe T, Sakai Y | title = Hermaphroditism and Mating Systems in Fish |pages=31–62 |place=Singapore |publisher=Springer Nature |language=en |doi=10.1007/978-981-19-6095-6_2 |isbn=978-981-19-6095-6 }}</ref> Sequential hermaphrodism occurs when gonadal sex redifferentiation takes place, often due to a decrease in the population of a specific sex. This form of hermaphrodism has taken upon three modes—protogyny, protandry, and bi-directional sex change.<ref name=":3">{{cite journal | vauthors = Kobayashi Y, Nagahama Y, Nakamura M | title = Diversity and plasticity of sex determination and differentiation in fishes | journal = Sexual Development | volume = 7 | issue = 1–3 | pages = 115–125 | date = 31 August 2012 | pmid = 22948719 | doi = 10.1159/000342009 }}</ref>
 
Protogynous sex change is the female to male gonadal redifferentiation, and it is often found within species that practice haremic polygyny, or one male reproducing with many females. When socially dominant males disappear, larger initial phase female fish will undergo sex change to become terminal phase males. In this, the ovaries are constructed to mature, functional testis. Protogyny sex change has been found within fish species such as the three-spot wrasse (''Halichoreres trimaculatas'') and the saddleback wrasse (''Thalassoma duperrey'') with a decline in plasma estrogen contributing to testis development.<ref name=":3" />
 
In contrast, protandrous sex change is the male to female gonadal redifferentiation, but it is also triggered by the disappearance of the conspecific dominant, in this case the female. While protogynous fish are found within species dominated by larger males, protandrous fish are within large female dominant species, such as the clown fish (''Amphiprion'').<ref name=":3" /> <ref>{{cite journal | vauthors = Casas L, Saborido-Rey F | title = Environmental Cues and Mechanisms Underpinning Sex Change in Fish | journal = Sexual Development | volume = 15 | issue = 1–3 | pages = 108–121 | date = 10 June 2021 | pmid = 34111868 | pmc = 8491468 | doi = 10.1159/000515274 }}</ref> Within the clown fish populations, males develop bi-sexual gonads—mature testis and immature ovaries—while the dominant females only possess ovaries. In cases of protandrous sex change, the immature ovarian tissues develop and the testicular tissues deteriorate due to changes in the activity of gonadal steroid hormones such as estrogen.<ref name=":3" />
 
Bi-directional, or serial, sex change occurs when hermaphrodites are capable of changing their sex in either direction, possibly multiple times. Some fish species are capable of this sex change due to the presence of both ovaries and testis, with only one gonad actively producing gametic cells at a time. The activation of a gonad is possible through changes in expression of the gonadotropin receptors. This primarily occurs in cases of male-male and female-female mating pairs, with the smaller male changing to female or the larger female changing to male due to the disappearance of the respective sex.<ref name=":2" /> This can be found in the Okinawa rubble gobiid fish (''Trimma okinawae'') whose mating system consists of a polygynous harem. When the dominant male is removed, the largest female changes its sex to male; if the dominant male is reintroduced, the sex can be reversed back to female.<ref name=":3" />
 
==== Induced reversal in aquaculture industry ====
In aquaculture, sex control is important due to the role of sex in growth and reproduction. In fishes, growth rates can be different between sexes. These differences can affect their economic value. Producing a monosex fish population can improve product quality and therefore generates higher financial profit.<ref name="Budd_2015">{{cite journal| vauthors = Budd AM, Banh QQ, Domingos JA, Jerry DR |date=2015-05-28|title=Sex Control in Fish: Approaches, Challenges and Opportunities for Aquaculture |journal=Journal of Marine Science and Engineering|language=en|volume=3|issue=2|pages=329–355|doi=10.3390/jmse3020329 |doi-access=free}}</ref>
 
Hormone-induced sex reversal is the most frequent method used in aquaculture. It consists of exposing sexually undifferentiated fishes to [[sex steroid]]s.<ref>{{Cite journal|last=Yamamoto|first=Toki-O. |vauthors name-list-style= =Yamamoto vancTO |date=1953|title=Artificially induced sex-reversal in genotypic males of the medaka (Oryzias latipes)|journal=Journal of Experimental Zoology |volume=123|issue=3|pages=571–594|doi=10.1002/jez.1401230309 |bibcode=1953JEZ...123..571Y }}</ref><ref>{{Cite journal| vauthors = Pandian TJ, Sheela SG |date=1995|title=Hormonal induction of sex reversal in fish|journal=Aquaculture|volume=138|issue=1–4|pages=1–22|doi=10.1016/0044-8486(95)01075-0|bibcode=1995Aquac.138....1P |issn=0044-8486}}</ref> There are other methods to induced sex reversal in fishes such as chromosomal/genetic manipulation, hybridization, or treatments influencing sex determination or gonad differentiation (e.g. temperature, population density, pH, social factors).<ref name="Budd_2015" />
 
=== In reptilesamphibians ===
Sex is genetically determined in [[amphibian]]s.<ref>{{cite book |last1 vauthors = Schmid |first1=MichaelM, |last2=Steinlein |first2=ClausC | name-list-stylechapter = vanc |title=Sex chromosomes, sex-linked genes, and sex determination in the vertebrate class Amphibia |date title =2001|work=Experientia SupplementumGenes and Mechanisms in Vertebrate Sex Determination | issue = 91 | pages = 143–176 |publisher date =Birkhäuser Basel2001 |isbn pmid =978-3-0348-7783-1 11301597 | doi = 10.1007/978-3-0348-7781-7_8 |pmid publisher =11301597 Birkhäuser Basel | isbn = 978-3-0348-7783-1 | series = Experientia Supplementum | volume = 91 }}</ref><ref>{{Cite journal|last1=Hillis|first1=David M.|last2vauthors =Green|first2=David M.Hillis |DM, name-list-style =Green vancDM |date=1990|title=Evolutionary changes of heterogametic sex in the phylogenetic history of amphibians|journal=Journal of Evolutionary Biology|volume=3|issue=1–2|pages=49–64|doi=10.1046/j.1420-9101.1990.3010049.x|s2cid=83609311|issn=1010-061X|doi-access=free}}</ref> Temperature-induced sex reversal has been documented in some species of anuran and caudate amphibians. Temperature only can have an effect on sex differentiation during a window period called thermosensitive period (TSP) which varies among species.<ref>{{Cite journal|last=Witschi|first=Emil |vauthors name-list-style= =Witschi vancE |date=1929|title=Studies on sex differentiation and sex determination in amphibians. II. Sex reversal in female tadpoles of Rana sylvatica following the application of high temperature|journal=Journal of Experimental Zoology|volume=52|issue=2|pages=267–291|doi=10.1002/jez.1400520203|bibcode=1929JEZ....52..267W |issn=0022-104X}}</ref><ref>{{cite book |last1 vauthors = Flament |first1=StéphaneS, |last2=Chardard |first2=DominiqueD, |last3=Chesnel |first3=AmanAD, d|last4=Dumond H |first4title=HélèneHormones |and name-list-styleReproduction =of vancVertebrates |titlechapter=Sex Determination and Sexual Differentiation in Amphibians|date=2011|work=Hormones and Reproduction of Vertebrates|pages=1–19 |publisher=Elsevier |isbn=978-0-12-374932-1|doi=10.1016/b978-0-12-374932-1.00014-7}}</ref><ref>{{cite journal | vauthors = Sakata N, Tamori Y, Wakahara M | title = P450 aromatase expression in the temperature-sensitive sexual differentiation of salamander (Hynobius retardatus) gonads | journal = The International Journal of Developmental Biology | volume = 49 | issue = 4 | pages = 417–25417–425 | date = 2005 | pmid = 15968587 | doi = 10.1387/ijdb.041916ns | doi-access = free }}</ref> Tadpoles or larvae exposed to specific higher or lower temperatures, depending on the temperature thresholds of the species, can differentiate gonads that do not align with their primary sexual fate.<ref>{{cite journal | vauthors = Flament S | title = Sex Reversal in Amphibians | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 267–278 | date = 2016 | pmid = 27648840 | doi = 10.1159/000448797 | doi-access = free }}</ref>
 
Amphibian sex reversal can be also induced by exposure to sex steroid and pollutants. Endocrine disruptors can affect gonad differentiation, and therefore induce sex reversal. Exposure to ethylnyl estradiol (EE<sub>2</sub>) and bisphenol A (BPA) induces feminizing effects.<ref>{{cite journal | vauthors = Bhandari RK, Deem SL, Holliday DK, Jandegian CM, Kassotis CD, Nagel SC, Tillitt DE, Vom Saal FS, Rosenfeld CS | display-authors = 6 | title = Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species | journal = General and Comparative Endocrinology | volume = 214 | pages = 195–219 | date = April 2015 | pmid = 25277515 | doi = 10.1016/j.ygcen.2014.09.014 }}</ref> Masculinizing effects can be induced by exposure to the drug trenbolone, used in cattle.<ref>{{cite journal | vauthors = Olmstead AW, Kosian PA, Johnson R, Blackshear PE, Haselman J, Blanksma C, Korte JJ, Holcombe GW, Burgess E, Lindberg-Livingston A, Bennett BA, Woodis KK, Degitz SJ | display-authors = 6 | title = Trenbolone causes mortality and altered sexual differentiation in Xenopus tropicalis during larval development | journal = Environmental Toxicology and Chemistry | volume = 31 | issue = 10 | pages = 2391–82391–2398 | date = October 2012 | pmid = 22847831 | doi = 10.1002/etc.1965 | s2cid = 22489522 }}</ref>
 
Research <ref>{{cite journal | vauthors = Lambert MR, Tran T, Kilian A, Ezaz T, Skelly DK | title = Molecular evidence for sex reversal in wild populations of green frogs (<i>Rana clamitans</i>) | journal = PeerJ | volume = 7 | pages = e6449 | date = 2019-02-08 | pmid = 30775188 | pmc = 6369831 | doi = 10.7717/peerj.6449 | doi-access = free }}</ref> in wild populations of the North American green frog has demonstrated that sex reversal is common. This work shows that genetic females sex reverse into phenotypic males and that genetic males sex reverse into phenotypic females, providing evidence that sex reversal can be bidirectional in amphibians. While [[Endocrine disruptor|endocrine disrupting chemical]] contamination is known from laboratory experiments to cause sex reversal in amphibians,<ref>{{cite news | url = https://news.yahoo.com/s/afp/20070227/sc_afp/scienceenvironmentanimalssexfrogs_070227120242 | title = Pollutants change 'he' frogs into 'she' frogs | work= Yahoo! News | access-date = 2007-03-01 | year = 2007 |archive-url = https://web.archive.org/web/20070302073022/http://news.yahoo.com/s/afp/20070227/sc_afp/scienceenvironmentanimalssexfrogs_070227120242 |archive-date = March 2, 2007}}</ref> sex reversal in green frogs occurs irrespective of contamination, suggesting sex reversal is a natural process in amphibians <ref>{{cite news | url = https://www.nationalgeographic.com/animals/article/frogs-reverse-sex-more-often-than-thought | archive-url = https://web.archive.org/web/20210220224800/https://www.nationalgeographic.com/animals/article/frogs-reverse-sex-more-often-than-thought | url-status = dead | archive-date = February 20, 2021 | title = Healthy frogs can mysteriously reverse their sex | work= National Geographic}}</ref>
 
=== In birdsreptiles ===
Sex in reptiles can be determined genetically (GSD), environmentally (ESD) or by an interaction of both.<ref name="Holleley_2015">{{cite journal | vauthors = Holleley CE, O'Meally D, Sarre SD, Marshall Graves JA, Ezaz T, Matsubara K, Azad B, Zhang X, Georges A | display-authors = 6 | title = Sex reversal triggers the rapid transition from genetic to temperature-dependent sex | journal = Nature | volume = 523 | issue = 7558 | pages = 79–82 | date = July 2015 | pmid = 26135451 | doi = 10.1038/nature14574 | s2cid = 1741119 | bibcode = 2015Natur.523...79H | s2cid = 1741119 }}</ref> Sex reversal has been documented in detail in wild populations of the central bearded dragon ''[[Central bearded dragon|Pogona vitticeps]],'' and in the eastern three-lined skink ''[[Eastern three-lined skink|Bassiana duperreyi]].'' In these species, their genetically determined sex is overridden by temperature influence.<ref>{{cite journal | vauthors = Ezaz T, Quinn AE, Miura I, Sarre SD, Georges A, Marshall Graves JA | title = The dragon lizard Pogona vitticeps has ZZ/ZW micro-sex chromosomes | journal = Chromosome Research | volume = 13 | issue = 8 | pages = 763–76763–776 | date = 2005 | pmid = 16331408 | doi = 10.1007/s10577-005-1010-9 | s2cid = 4934610 }}</ref><ref name="Holleley_2015" /><ref name=":0" />
 
Further, there are certain primitive reptiles (some chelonians, some crocodilians, and one lizard species) that undergo Temperature-dependent Sex Determination ([[Temperature-dependent sex determination|TSD]]) during their egg incubation (a form of ESD).<ref>{{Cite journal | vauthors = Bull JJ |date=1980 |title=Sex Determination in Reptiles |url=https://www.jstor.org/stable/2826077 |journal=The Quarterly Review of Biology |volume=55 |issue=1 |pages=3–21 |doi=10.1086/411613 |jstor=2826077 |issn=0033-5770}}</ref><ref name=":1">{{cite journal | vauthors = Wibbels T, Bull JJ, Crews D | title = Chronology and morphology of temperature-dependent sex determination | journal = The Journal of Experimental Zoology | volume = 260 | issue = 3 | pages = 371–381 | date = December 1991 | pmid = 1744617 | doi = 10.1002/jez.1402600311 }}</ref> [[Temperature-dependent sex determination|TSD]] functions within a transitional range of temperature (TRT) that influences the sex of the egg and a pivotal temperature that would give rise to a 50:50 chance of females:males.<ref name=":1" /> For these reptiles that exhibit [[Temperature-dependent sex determination|TSD]], the egg is sensitive to temperature in the middle-third of incubation.<ref>{{cite journal | vauthors = Crews D, Bergeron JM, Bull JJ, Flores D, Tousignant A, Skipper JK, Wibbels T | title = Temperature-dependent sex determination in reptiles: proximate mechanisms, ultimate outcomes, and practical applications | journal = Developmental Genetics | volume = 15 | issue = 3 | pages = 297–312 | date = January 1994 | pmid = 8062460 | doi = 10.1002/dvg.1020150310 }}</ref> The sex of the eggs could be reversed or "corrected" (shifting from one sex, to another, and back to the original) during later stages of the middle-third of incubation if the temperature is shifted.<ref name=":1" />
 
Sex reversal in reptiles can be induced by hormonal manipulation, treatments influencing sex determination (e.g. temperature) or by inhibition of the [[aromatase]] gene (CYP19A1) which causes sex reversal from female to male phenotype.<ref name=":0">{{cite journal | vauthors = Holleley CE, Sarre SD, O'Meally D, Georges A | title = Sex Reversal in Reptiles: Reproductive Oddity or Powerful Driver of Evolutionary Change? | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 279–287 | date = 2016 | pmid = 27794577 | doi = 10.1159/000450972 | s2cid = 27199048 }}</ref> Further, estradiol-17β has been shown to reverse the sex of turtle species when injected into incubating eggs. These eggs were originally placed in are male producing temperatures, but with the estradiol-17β treatment, they would generate females.<ref>{{cite journal | vauthors = Wibbels T, Bull JJ, Crews D | title = Synergism between temperature and estradiol: a common pathway in turtle sex determination? | journal = The Journal of Experimental Zoology | volume = 260 | issue = 1 | pages = 130–134 | date = October 1991 | pmid = 1791420 | doi = 10.1002/jez.1402600117 }}</ref> However, hormone-based sex reversal would be dependent on the gonadal development stages of the embryo (the middle-third of incubation).<ref>{{cite journal | vauthors = Wibbels T, Gideon P, Bull JJ, Crews D | title = Estrogen- and temperature-induced medullary cord regression during gonadal differentiation in a turtle | journal = Differentiation; Research in Biological Diversity | volume = 53 | issue = 3 | pages = 149–154 | date = July 1993 | pmid = 8405765 | doi = 10.1111/j.1432-0436.1993.tb00703.x }}</ref>
 
=== In amphibiansbirds ===
In birds, sex reversal has been documented in natural and experimental conditions. [[Sex steroid]] manipulation can(such as hormones including androgens, estrogens, and progestogens<ref>{{cite journal |vauthors=Coveney D, Shaw G, Renfree MB |date=August 2001 |title=Estrogen-induced gonadal sex reversal in the tammar wallaby |journal=Biology of Reproduction |volume=65 |issue=2 |pages=613–621 |doi=10.1095/biolreprod65.2.613 |pmid=11466233|doi-access=free }}</ref>) can induce sex reversal in birds by interacting with vertebrae and hormone receptors. Aromatase inhibitors injected into chicken eggs before the gonadal differentiation stage induce testis development in ZW embryos.<ref>{{cite journal | vauthors = Major AT, Smith CA | title = Sex Reversal in Birds | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 288–300 | date = 2016 | pmid = 27529790 | doi = 10.1159/000448365 | s2cid = 5525642 | url = https://research.monash.edu/en/publications/1e9a5f3f-4b49-43c7-a269-bba0db289078 }}</ref>
Sex is genetically determined in [[amphibian]]s.<ref>{{cite book |last1=Schmid |first1=Michael |last2=Steinlein |first2=Claus | name-list-style = vanc |title=Sex chromosomes, sex-linked genes, and sex determination in the vertebrate class Amphibia|date=2001|work=Experientia Supplementum|issue=91 |pages=143–176|publisher=Birkhäuser Basel|isbn=978-3-0348-7783-1|doi=10.1007/978-3-0348-7781-7_8|pmid=11301597}}</ref><ref>{{Cite journal|last1=Hillis|first1=David M.|last2=Green|first2=David M. | name-list-style = vanc |date=1990|title=Evolutionary changes of heterogametic sex in the phylogenetic history of amphibians|journal=Journal of Evolutionary Biology|volume=3|issue=1–2|pages=49–64|doi=10.1046/j.1420-9101.1990.3010049.x|s2cid=83609311|issn=1010-061X|doi-access=free}}</ref> Temperature-induced sex reversal has been documented in some species of anuran and caudate amphibians. Temperature only can have an effect on sex differentiation during a window period called thermosensitive period (TSP) which varies among species.<ref>{{Cite journal|last=Witschi|first=Emil | name-list-style = vanc |date=1929|title=Studies on sex differentiation and sex determination in amphibians. II. Sex reversal in female tadpoles of Rana sylvatica following the application of high temperature|journal=Journal of Experimental Zoology|volume=52|issue=2|pages=267–291|doi=10.1002/jez.1400520203|issn=0022-104X}}</ref><ref>{{cite book |last1=Flament |first1=Stéphane |last2=Chardard |first2=Dominique |last3=Chesnel |first3=Aman d|last4=Dumond |first4=Hélène | name-list-style = vanc |title=Sex Determination and Sexual Differentiation in Amphibians|date=2011|work=Hormones and Reproduction of Vertebrates|pages=1–19 |publisher=Elsevier |isbn=978-0-12-374932-1|doi=10.1016/b978-0-12-374932-1.00014-7}}</ref><ref>{{cite journal | vauthors = Sakata N, Tamori Y, Wakahara M | title = P450 aromatase expression in the temperature-sensitive sexual differentiation of salamander (Hynobius retardatus) gonads | journal = The International Journal of Developmental Biology | volume = 49 | issue = 4 | pages = 417–25 | date = 2005 | pmid = 15968587 | doi = 10.1387/ijdb.041916ns | doi-access = free }}</ref> Tadpoles or larvae exposed to specific higher or lower temperatures, depending on the temperature thresholds of the species, can differentiate gonads that do not align with their primary sexual fate.<ref>{{cite journal | vauthors = Flament S | title = Sex Reversal in Amphibians | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 267–278 | date = 2016 | pmid = 27648840 | doi = 10.1159/000448797 | doi-access = free }}</ref>
 
Sex reversal in chickens form almost identical phenotypes, which characteristics of an expression of the individual genotype with the environment and the genotype being the presentation or its makeup. The sex reversal of bird's ties into mammals as well. However, the sex chromosomes are different: males have ZZ while females have ZW sex chromosomes. The sex orientation in birds is a mix of direct genetic and hormonal mechanisms. Birds show the most amazing sexually dimorphism that are seen in vertebrates. These birds can come from the same species having two different forms. The male bird is bright colored while the female bird is drab or "dull" in color with no radiant or vibrant color to it at all.
Amphibian sex reversal can be also induced by exposure to sex steroid and pollutants. Endocrine disruptors can affect gonad differentiation, and therefore induce sex reversal. Exposure to ethylnyl estradiol (EE<sub>2</sub>) and bisphenol A (BPA) induces feminizing effects.<ref>{{cite journal | vauthors = Bhandari RK, Deem SL, Holliday DK, Jandegian CM, Kassotis CD, Nagel SC, Tillitt DE, Vom Saal FS, Rosenfeld CS | display-authors = 6 | title = Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species | journal = General and Comparative Endocrinology | volume = 214 | pages = 195–219 | date = April 2015 | pmid = 25277515 | doi = 10.1016/j.ygcen.2014.09.014 }}</ref> Masculinizing effects can be induced by exposure to the drug trenbolone, used in cattle.<ref>{{cite journal | vauthors = Olmstead AW, Kosian PA, Johnson R, Blackshear PE, Haselman J, Blanksma C, Korte JJ, Holcombe GW, Burgess E, Lindberg-Livingston A, Bennett BA, Woodis KK, Degitz SJ | display-authors = 6 | title = Trenbolone causes mortality and altered sexual differentiation in Xenopus tropicalis during larval development | journal = Environmental Toxicology and Chemistry | volume = 31 | issue = 10 | pages = 2391–8 | date = October 2012 | pmid = 22847831 | doi = 10.1002/etc.1965 | s2cid = 22489522 }}</ref>
 
=== In mammals ===
Research <ref>{{cite journal | vauthors = Lambert MR, Tran T, Kilian A, Ezaz T, Skelly DK | title = Rana clamitans) | journal = PeerJ | volume = 7 | pages = e6449 | date = 2019-02-08 | pmid = 30775188 | pmc = 6369831 | doi = 10.7717/peerj.6449 }}</ref> in wild populations of the North American green frog has demonstrated that sex reversal is common. This work shows that genetic females sex reverse into phenotypic males and that genetic males sex reverse into phenotypic females, providing evidence that sex reversal can be bidirectional in amphibians. While [[Endocrine disruptor|endocrine disrupting chemical]] contamination is known from laboratory experiments to cause sex reversal in amphibians,<ref>{{cite news | url = https://news.yahoo.com/s/afp/20070227/sc_afp/scienceenvironmentanimalssexfrogs_070227120242 | title = Pollutants change 'he' frogs into 'she' frogs | work= Yahoo! News | access-date = 2007-03-01 | year = 2007 |archive-url = https://web.archive.org/web/20070302073022/http://news.yahoo.com/s/afp/20070227/sc_afp/scienceenvironmentanimalssexfrogs_070227120242 |archive-date = March 2, 2007}}</ref> sex reversal in green frogs occurs irrespective of contamination, suggesting sex reversal is a natural process in amphibians <ref>{{cite news | url = https://www.nationalgeographic.com/animals/article/frogs-reverse-sex-more-often-than-thought | title = Healthy frogs can mysteriously reverse their sex | work= National Geographic}}</ref>
Sex reversal in mammals has been documented in domestic species such as [[cattle]], [[water buffalo]], [[horse]]s, [[dog]]s, [[cat]]s, [[pig]]s, [[goat]]s, etc. Sex reversal in these species usually relates to genetic changes and the resulting phenotype is often associated with gonadal malformation.<ref name="Parma_2016">{{cite journal | vauthors = Parma P, Veyrunes F, Pailhoux E | title = Sex Reversal in Non-Human Placental Mammals | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 326–344 | date = 2016 | pmid = 27529721 | doi = 10.1159/000448361 | hdl-access = 2434/429122free | s2cid = 21751654 | hdl-access = free2434/429122 }}</ref> Natural sex reversal without disruptive effects on fertility has been documented in several rodents, including ''[[Wood lemming|Myopus schisticolor]], [[Arctic lemming|Dicrostonyx torquatus]], [[Akodon]], [[African pygmy mouse|Mus minutoides]], [[Cabrera's vole|Microtus cabrerae]].'' In these species some individuals genetically determined as males develop typical ovarian structure.<ref>{{cite journal | vauthors = Rahmoun M, Perez J, Saunders PA, Boizet-Bonhoure B, Wilhelm D, Poulat F, Veyrunes F | title = Anatomical and molecular analyses of XY ovaries from the African pygmy mouse Mus minutoides | journal = Sexual Development | volume = 8 | issue = 6 | pages = 356–63356–363 | date = 2014 | pmid = 25359508 | doi = 10.1159/000368664 | s2cid = 19650896 }}</ref> In these rodents species, sex reversal mainly occurs after mutational events.<ref name="Parma_2016" />
 
In mammals, sex reversal occurs when the gonadal or sexual phenotype does not align with the genetic sex determined by the XX/XY or ZZ/ZW chromosomal system. The development of an ovary and female phenotype in an individual with XY chromosomes represents the instance of sex reversal in mammals. Research has identified various genes involved in mammalian sex determination and differentiation. SRY (Sex-determining Region Y) in humans and mice is one of the sex-determination genes that plays a significant function in initiating male development. Mutations or anomalies can affect these sex-determining genes resulting in sex reversal phenotypes. <ref>{{cite book | vauthors = Gilbert SF | chapter = Chromosomal Sex Determination in Mammals |date=2000 | title = Developmental Biology. | edition = 6th | url=https://www.ncbi.nlm.nih.gov/books/NBK9967/ |access-date=2024-03-25 |publisher=Sinauer Associates |language=en}}</ref>
=== In reptiles ===
Sex in reptiles can be determined genetically (GSD), environmentally (ESD) or by an interaction of both.<ref name="Holleley_2015">{{cite journal | vauthors = Holleley CE, O'Meally D, Sarre SD, Marshall Graves JA, Ezaz T, Matsubara K, Azad B, Zhang X, Georges A | display-authors = 6 | title = Sex reversal triggers the rapid transition from genetic to temperature-dependent sex | journal = Nature | volume = 523 | issue = 7558 | pages = 79–82 | date = July 2015 | pmid = 26135451 | doi = 10.1038/nature14574 | bibcode = 2015Natur.523...79H | s2cid = 1741119 }}</ref> Sex reversal has been documented in detail in wild populations of the central bearded dragon ''[[Central bearded dragon|Pogona vitticeps]],'' and in the eastern three-lined skink ''[[Eastern three-lined skink|Bassiana duperreyi]].'' In these species, their genetically determined sex is overridden by temperature influence.<ref>{{cite journal | vauthors = Ezaz T, Quinn AE, Miura I, Sarre SD, Georges A, Marshall Graves JA | title = The dragon lizard Pogona vitticeps has ZZ/ZW micro-sex chromosomes | journal = Chromosome Research | volume = 13 | issue = 8 | pages = 763–76 | date = 2005 | pmid = 16331408 | doi = 10.1007/s10577-005-1010-9 | s2cid = 4934610 }}</ref><ref name="Holleley_2015" /><ref name=":0" />
 
Additionally, hormonal factors play a significant role in sex reversal among mammals. Estrogen and ovarian hormones facilitate female development whereas testosterone and anti-Müllerian hormone (AMH) produced by the testes promote male development.<ref name = "Navara_2013">{{cite journal | vauthors = Navara KJ | title = Hormone-mediated adjustment of sex ratio in vertebrates | journal = Integrative and Comparative Biology | volume = 53 | issue = 6 | pages = 877–887 | date = December 2013 | pmid = 23892413 | doi = 10.1093/icb/ict081 }}</ref> However, disruptions in hormone signaling pathways can lead to sex reversal. For instance, exposure to estrogen during critical periods of development can interfere with normal hormone levels and can cause sex reversal phenotypes.<ref>{{cite journal | vauthors = Coveney D, Shaw G, Renfree MB | title = Estrogen-induced gonadal sex reversal in the tammar wallaby | journal = Biology of Reproduction | volume = 65 | issue = 2 | pages = 613–621 | date = August 2001 | pmid = 11466233 | doi = 10.1095/biolreprod65.2.613 | doi-access = free }}</ref>
Sex reversal in reptiles can be induced by hormonal manipulation, treatments influencing sex determination (e.g. temperature) or by inhibition of the [[aromatase]] gene (CYP19A1) which causes sex reversal from female to male phenotype.<ref name=":0">{{cite journal | vauthors = Holleley CE, Sarre SD, O'Meally D, Georges A | title = Sex Reversal in Reptiles: Reproductive Oddity or Powerful Driver of Evolutionary Change? | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 279–287 | date = 2016 | pmid = 27794577 | doi = 10.1159/000450972 | s2cid = 27199048 }}</ref>
 
Sex reversal in mammals can be impacted by ecological factors such as habitat destruction, and resource availability. Changes in environmental conditions may influence the frequency of sex reversal within mammalian populations, ultimately affecting population dynamics and ecosystem functioning. Understanding sex reversal in mammals is crucial for wildlife conservation efforts, particularly in species facing threats such as habitat loss, and pollution. Sex reversal can potentially influence the long-term viability of populations by altering population demographics, reproductive success, and genetic diversity.<ref>{{cite journal | vauthors = Stelkens RB, Wedekind C | title = Environmental sex reversal, Trojan sex genes, and sex ratio adjustment: conditions and population consequences | journal = Molecular Ecology | volume = 19 | issue = 4 | pages = 627–646 | date = February 2010 | pmid = 20088884 | doi = 10.1111/j.1365-294X.2010.04526.x | bibcode = 2010MolEc..19..627S }}</ref>
=== In birds ===
In birds, sex reversal has been documented in natural and experimental conditions. [[Sex steroid]] manipulation can induced sex reversal in birds. Aromatase inhibitors injected into chicken eggs before the gonadal differentiation stage induce testis development in ZW embryos.<ref>{{cite journal | vauthors = Major AT, Smith CA | title = Sex Reversal in Birds | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 288–300 | date = 2016 | pmid = 27529790 | doi = 10.1159/000448365 | s2cid = 5525642 }}</ref>
 
Furthermore, sex reversal can lead to behavioral adaptations within mammalian populations as individuals navigate their altered reproductive roles and social dynamics. Research findings have demonstrated changes in mating behaviors, dominance hierarchies, and social interactions among individuals with sex reversal phenotypes. The evolutionary significance of sex reversal and its impact on population dynamics and social structure can be studied by understanding the mechanism of behavioral adaptations.<ref>{{cite journal | vauthors = Weber C, Capel B | title = Sex reversal | journal = Current Biology | volume = 28 | issue = 21 | pages = R1234–R1236 | date = November 2018 | pmid = 30399341 | pmc = 8941919 | doi = 10.1016/j.cub.2018.09.043 | bibcode = 2018CBio...28R1234W }}</ref>
=== In mammals ===
Sex reversal in mammals has been documented in domestic species such as [[cattle]], [[water buffalo]], [[horse]]s, [[dog]]s, [[cat]]s, [[pig]]s, [[goat]]s, etc. Sex reversal in these species usually relates to genetic changes and the resulting phenotype is often associated with gonadal malformation.<ref name="Parma_2016">{{cite journal | vauthors = Parma P, Veyrunes F, Pailhoux E | title = Sex Reversal in Non-Human Placental Mammals | journal = Sexual Development | volume = 10 | issue = 5–6 | pages = 326–344 | date = 2016 | pmid = 27529721 | doi = 10.1159/000448361 | hdl = 2434/429122 | s2cid = 21751654 | hdl-access = free }}</ref> Natural sex reversal without disruptive effects on fertility has been documented in several rodents, including ''[[Wood lemming|Myopus schisticolor]], [[Arctic lemming|Dicrostonyx torquatus]], [[Akodon]], [[African pygmy mouse|Mus minutoides]], [[Cabrera's vole|Microtus cabrerae]].'' In these species some individuals genetically determined as males develop typical ovarian structure.<ref>{{cite journal | vauthors = Rahmoun M, Perez J, Saunders PA, Boizet-Bonhoure B, Wilhelm D, Poulat F, Veyrunes F | title = Anatomical and molecular analyses of XY ovaries from the African pygmy mouse Mus minutoides | journal = Sexual Development | volume = 8 | issue = 6 | pages = 356–63 | date = 2014 | pmid = 25359508 | doi = 10.1159/000368664 | s2cid = 19650896 }}</ref> In these rodents species, sex reversal mainly occurs after mutational events.<ref name="Parma_2016" />
 
== See also ==
* [[Sex-determination system]]
* [[Sequential hermaphroditism]]
* [[Temperature-dependent sex determination]]
* [[Teratogenesis]]
 
== References ==
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[[Category:Embryology]]
[[Category:Sexuality]]
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