Sexual differentiation

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Sexual differentiation
2915 Sexual Differentation-02.jpg
Differentiation of the male and female reproductive systems does not occur until the fetal period of development.
Anatomical terminology

Sexual differentiation is the process of development of the sex differences between males and females from an undifferentiated zygote. [1] [2] Sex determination is often distinct from sex differentiation; sex determination is the designation for the development stage towards either male or female, while sex differentiation is the pathway towards the development of the phenotype. [3]

Contents

In many species, testicular or ovarian differentiation begins with appearance of Sertoli cells in males and granulosa cells in females. [4] [ citation needed ]

As male and female individuals develop from embryos into mature adults, sex differences at many levels develop, such as genes, chromosomes, gonads, hormones, anatomy, and psyche. Beginning with determination of sex by genetic and/or environmental factors, humans and other organisms proceed down different pathways of differentiation as they grow and develop.

Sex determination systems

Humans, many mammals, insects and other animals have an XY sex-determination system. Humans have forty-six chromosomes, including two sex chromosomes, XX in females and XY in males. The Y chromosome must carry at least one essential gene which determines testicular formation (originally termed TDF). [5] In transgenic XX mice (and some human XX males), SRY alone is sufficient to induce male differentiation. [6]

Other chromosomal systems exist in other taxa, such as the ZW sex-determination system in birds [7] and the XO system in insects. [8]

Environmental sex determination refers to the determination (and then differentiation) of sex via non-genetic cues like social factors, temperature, and available nutrients. In some species, such as the hermaphroditic clownfish, sex differentiation can occur more than once as a response to different environmental cues, [9] offering an example of how sex differentiation does not always follow a typical linear path.

There have been multiple transitions between environmental and genetic sex determination systems in reptiles over time, [10] and recent studies have shown that temperature can sometimes override sex determination via chromosomes. [11]

Humans

The Human Y Chromosome showing the SRY gene which codes for a protein regulating sexual differentiation. YChromShowingSRY2.png
The Human Y Chromosome showing the SRY gene which codes for a protein regulating sexual differentiation.

The early stages of human differentiation appear to be quite similar to the same biological processes in other mammals and the interaction of genes, hormones and body structures is fairly well understood. In the first weeks of gestation, a fetus is anatomically indistinguishable as male or female and lacks production of any particular sex hormones. Only a karyotype distinguishes male from female. Specific genes induce gonadal differences, which produce hormonal differences, which cause anatomic differences, leading to psychological and behavioral differences, some of which are innate and some induced by the social environment.

Various processes are involved in the development of sex differences in humans. Sexual differentiation in humans includes development of different genitalia and the internal genital tracts, breasts, body hair, and plays a role in gender identification. [12] [ better source needed ]

The development of sexual differences begins with the XY sex-determination system that is present in humans, and complex mechanisms are responsible for the development of the phenotypic differences between male and female humans from an undifferentiated zygote. [13] Atypical sexual development, and ambiguous genitalia, can be a result of genetic and hormonal factors. [14]

The differentiation of other parts of the body than the sex organ creates the secondary sex characteristics. Sexual dimorphism of skeletal structure develops during childhood, and becomes more pronounced at adolescence.

Other animals

The first genes involved in the cascade of differentiation can differ between taxa and even between closely related species. For example: in zebrafish the first known gene to induce male differentiation is the amh gene, in tilapia it is tDmrt1, and in southern catfish it is foxl2. [15]

In fish, due to the fact that modes of reproduction range from gonochorism (distinct sexes) to self-fertilizing hermaphroditism (where one organism has functioning gonadal features of multiple sexes), sexual differentiation is complex. Two major pathways in gonochores exist: one with a nonfunctional, undifferentiated phase leading to delayed differentiation (secondary), and one without (primary), where differences between the sexes can be noted prior to hatching. [4] Secondary gonochorists remain in the bipotential phase until a biotic or abiotic cue directs development down one pathway. Primary gonochorism, without an intersex phase, follows classical pathways of genetic sex determination, but can still be later influenced by the environment. [4] Differentiation pathways progress, and secondary sex characteristics such as anal fin bifurcation and ornamentation typically arise at puberty. [15]

In birds, thanks to research on Gallus gallus domesticus , it has been shown that determination of sex is likely cell-autonomous, i.e. that sex is determined in each somatic cell independently of, or in conjunction with, the hormone signaling that occurs in other species. [16] Studies on gynandromorph chickens showed that the mosaicism could not be explained by hormones alone, pointing to direct genetic factors, possibly one or a few Z-specific genes such as double-sex or DMRT1. [16]

Flexibility

The most intensively studied species, such as fruit flies, nematodes, and mice, reveal that evolutionarily, sex determination/differentiation systems are not wholly conserved and have evolved over time. [10] Beyond the presence or absence of chromosomes or social/environmental factors, sexual differentiation can be regulated in part by complex systems like the ratio of genes on X chromosomes and autosomes, protein production and transcription, and specific mRNA splicing. [10]

Differentiation pathways can be altered at many stages of the process. Sex reversal, where the development of a sexual phenotype is redirected during embryonic development, happens in the initiation phase of gonadal sex differentiation. Even in species where there is a well-documented master regulator gene, its effects can be overridden by a downstream gene. [17]

Furthermore, hermaphrodites serve as examples of the flexibility of sexual differentiation systems. Sequential hermaphrodites are organisms that possess reproductive capabilities of one sex, and then that sex changes. [18] Differentiated gonadal tissue of the organism's former sex degenerates, and new sex gonadal tissue grows and differentiates. [9] Organisms that have the physiological capability to reproduce as a male and as a female at the same time are known as simultaneous hermaphrodites. Some simultaneous hermaphroditic organisms, like certain species of goby, have distinctive male and female phases of reproduction and can flip back and forth, or "sex reverse", between the two. [19]

Socially-determined

In some species, such as sequentially hermaphroditic clownfish, changes in social environment can lead to sexual differentiation or sex reversal, i.e. differentiation in the opposite direction. [9] In clownfish, females are larger than males, and in social groups, there is typically one large female, multiple smaller males, and undifferentiated juveniles. If the female is removed from the group, the largest male changes sex, i.e. the former gonad tissue degenerates and new gonad tissue grows. Furthermore, the pathway of differentiation in activated in the largest juvenile, which becomes male. [9]

Alternative morphs

Sexual differentiation in a species does not have to produce one recognizable female type and one recognizable male type. In some species alternative morphs, or morphotypes, within one sex exist, such as flanged (larger than females, with large flap-like cheek-pads) and unflanged (about the same size as females, no cheek-pads) male orangutans, [20] and sometimes differences between male morphs can be more noticeable than differences between a male and a female within such species. [21] Furthermore, sexual selection can be involved in the development of different types of males with alternative reproductive strategies, such as sneaker and territorial males in dung beetles [22] or haremic males and pair-bonding males in the Nigerian cichlid fish P. pulcher. [15] [23] Sometimes alternative morphs are produced by genetic differences, and in other cases, the environment can be involved, demonstrating some degree of phenotypic plasticity. [24]

Brain differentiation

In many animals, differences in the exposure of a fetal brain to sex hormones are correlated with significant differences of brain structure and function, which correlate with adult reproductive behavior. [5] The causes of differences between the sexes are only understood in some species. Fetal sex differences in human brains coupled with early differences in experience may be responsible for sex differences observed in children between 4 years old and adolescence. [25]

Many individual studies in humans and other primates have found statistically significant sex differences in specific brain structures; however, some studies have found no sex differences, and some meta-analyses have called into question the over-generalization that women and men's brains function differently. [26] Males and females statistically differ in some aspects of their brains, but there are areas of the brain which appear not to be sexually differentiated at all. Some scholars describe human brain variation not as two distinct categories, and not even a maleness-femaleness continuum, but as mosaics. [27]

In birds, hypotheses of male-female brain sex differences have been challenged by recent findings that differences between groups can be at least partially explained by the individual's dominance rank. [28] Furthermore, the behavioral causes of brain sex differences have been enumerated in studies of sex differences between different mating systems. For example, males of a polygynous vole species with intrasexual male competition have better spatial learning and memory than the females of their own species, but also better spatial learning and memory than all sexes of other closely related species that are monogamous; thus the brain differences commonly seen as "sex differences" have been instead linked to competition. [29] Sexual selection does play a role in some species, though, as males who display more song behaviors are selected for by females⁠—so some sex differences in bird song brain regions seem to have been evolutionarily selected for over time. [29]

Related Research Articles

<span class="mw-page-title-main">Sex</span> Trait that determines an organisms sexually reproductive function

Sex is the trait that determines whether a sexually reproducing organism produces male or female gametes. During sexual reproduction, a male and a female gamete fuse to form a zygote, which develops into an offspring that inherits traits from each parent. By convention, organisms that produce smaller, more mobile gametes are called male, while organisms that produce larger, non-mobile gametes are called female. An organism that produces both types of gamete is hermaphrodite.

<span class="mw-page-title-main">XY sex-determination system</span> Method of determining sex

The XY sex-determination system is a sex-determination system used to classify many mammals, including humans, some insects (Drosophila), some snakes, some fish (guppies), and some plants. In this system, the sex of an individual is determined by a pair of sex chromosomes. Females have two of the same kind of sex chromosome (XX), and are called the homogametic sex. Males have two different kinds of sex chromosomes (XY), and are called the heterogametic sex.

<span class="mw-page-title-main">Sex-determination system</span> Biological system that determines the development of an organisms sex

A sex-determination system is a biological system that determines the development of sexual characteristics in an organism. Most organisms that create their offspring using sexual reproduction have two common sexes and a few less common intersex variations.

<span class="mw-page-title-main">Gonad</span> Gland that produces sex cells

A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sperm in the form of spermatozoa. The female gonad, the ovary, produces egg cells. Both of these gametes are haploid cells. Some hermaphroditic animals have a type of gonad called an ovotestis.

<span class="mw-page-title-main">Sexual dimorphism</span> Condition where males and females exhibit different characteristics

Sexual dimorphism is the condition where sexes of the same species exhibit different morphological characteristics, particularly characteristics not directly involved in reproduction. The condition occurs in most dioecious species, which consist of most animals and some plants. Differences may include secondary sex characteristics, size, weight, color, markings, or behavioral or cognitive traits. Male-male reproductive competition has evolved a diverse array of sexually dimorphic traits. Aggressive utility traits such as "battle" teeth and blunt heads reinforced as battering rams are used as weapons in aggressive interactions between rivals. Passive displays such as ornamental feathering or song-calling have also evolved mainly through sexual selection. These differences may be subtle or exaggerated and may be subjected to sexual selection and natural selection. The opposite of dimorphism is monomorphism, when both biological sexes are phenotypically indistinguishable from each other.

<span class="mw-page-title-main">Sex-determining region Y protein</span> Protein that initiates male sex determination in therian mammals

Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.

<span class="mw-page-title-main">Male</span> Sex of an organism which produces sperm

Male is the sex of an organism that produces the gamete known as sperm, which fuses with the larger female gamete, or ovum, in the process of fertilisation. A male organism cannot reproduce sexually without access to at least one ovum from a female, but some organisms can reproduce both sexually and asexually. Most male mammals, including male humans, have a Y chromosome, which codes for the production of larger amounts of testosterone to develop male reproductive organs.

<span class="mw-page-title-main">Male reproductive system</span> Reproductive system of the human male

The male reproductive system consists of a number of sex organs that play a role in the process of human reproduction. These organs are located on the outside of the body, and within the pelvis.

Sexual characteristics are physical traits of an organism which are indicative of or resultant from biological sexual factors. These include both primary sex characteristics, such as gonads, and secondary sex characteristics.

<span class="mw-page-title-main">Hypothalamic–pituitary–gonadal axis</span> Concept of regarding the hypothalamus, pituitary gland and gonadal glands as a single entity

The hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.

<span class="mw-page-title-main">XX male syndrome</span> Congenital condition where an individual with a 46,XX karyotype is male

XX male syndrome, also known as de la Chapelle syndrome, is a rare condition in which an individual with a 46,XX karyotype develops a male phenotype. Synonyms for XX male syndrome include 46,XX testicular difference of sex development

<span class="mw-page-title-main">Sex cords</span> Structures that develop from the genital ridges that further differentiate based on an embryos sex

Sex cords are embryonic structures which eventually will give rise (differentiate) to the adult gonads. They are formed from the genital ridges - which will develop into the gonads - in the first 2 months of gestation which depending on the sex of the embryo will give rise to male or female sex cords. These epithelial cells penetrate and invade the underlying mesenchyme to form the primitive sex cords. This occurs shortly before and during the arrival of the primordial germ cells (PGCs) to the paired genital ridges. If there is a Y chromosome present, testicular cords will develop via the Sry gene : repressing the female sex cord genes and activating the male. If there is no Y chromosome present the opposite will occur, developing ovarian cords. Prior to giving rise to sex cords, both XX and XY embryos have Müllerian ducts and Wolffian ducts. One of these structures will be repressed to induce the other to further differentiate into the external genitalia.

Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. One type of gonadal dysgenesis is the development of functionless, fibrous tissue, termed streak gonads, instead of reproductive tissue. Streak gonads are a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.

<span class="mw-page-title-main">Sexual differentiation in humans</span> Process of development of sex differences in humans

Sexual differentiation in humans is the process of development of sex differences in humans. It is defined as the development of phenotypic structures consequent to the action of hormones produced following gonadal determination. Sexual differentiation includes development of different genitalia and the internal genital tracts and body hair plays a role in sex identification.

<span class="mw-page-title-main">Temperature-dependent sex determination</span> Environmental sex determination by temperature during development

Temperature-dependent sex determination (TSD) is a type of environmental sex determination in which the temperatures experienced during embryonic/larval development determine the sex of the offspring. It is observed in reptiles and teleost fish, with some reports of it occurring in species of shrimp. TSD differs from the chromosomal sex-determination systems common among vertebrates. It is the most studied type of environmental sex determination (ESD). Some other conditions, e.g. density, pH, and environmental background color, are also observed to alter sex ratio, which could be classified either as temperature-dependent sex determination or temperature-dependent sex differentiation, depending on the involved mechanisms. As sex-determining mechanisms, TSD and genetic sex determination (GSD) should be considered in an equivalent manner, which can lead to reconsidering the status of fish species that are claimed to have TSD when submitted to extreme temperatures instead of the temperature experienced during development in the wild, since changes in sex ratio with temperature variation are ecologically and evolutionally relevant.

<span class="mw-page-title-main">Disorders of sex development</span> Medical conditions involving the development of the reproductive system

Disorders of sex development (DSDs), also known as differences in sex development or variations in sex characteristics (VSC), are congenital conditions affecting the reproductive system, in which development of chromosomal, gonadal, or anatomical sex is atypical.

<span class="mw-page-title-main">Prenatal hormones and sexual orientation</span> Hormonal theory of sexuality

The hormonal theory of sexuality holds that, just as exposure to certain hormones plays a role in fetal sex differentiation, such exposure also influences the sexual orientation that emerges later in the individual. Prenatal hormones may be seen as the primary determinant of adult sexual orientation, or a co-factor with genes, biological factors and/or environmental and social conditions, for males and females, but at the moment are just hypotheses, more studies will give an answer to this scientific challenge began more than 70 years ago.

46,XX/46,XY is a chimeric genetic condition characterized by the presence of some cells that express a 46,XX karyotype and some cells that express a 46,XY karyotype in a single human being. The cause of the condition lies in utero with the aggregation of two distinct blastocysts or zygotes into a single embryo, which subsequently leads to the development of a single individual with two distinct cell lines, instead of a pair of fraternal twins. 46,XX/46,XY chimeras are the result of the merging of two non-identical twins. This is not to be confused with mosaicism or hybridism, neither of which are chimeric conditions.

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. The process of sex reversal occurs during embryonic development or before gonad differentiation. In GSD species, sex reversal means that the sexual phenotype is discordant with the genetic/chromosomal sex. In TSD species, sex reversal means that the temperature/conditions that usually trigger the differentiation towards one sexual phenotype are producing the opposite sexual phenotype.

<span class="mw-page-title-main">Eric Vilain</span>

Eric Vilain is a physician-scientist and professor in the fields of Differences of Sex Development (DSDs) and precision medicine. He is the Associate Vice Chancellor for Scientific Affairs at the University of California, Irvine Health Affairs and also the director of the UCI Institute for Clinical and Translational Science. He previously was the director of the Center for Genetic Medicine Research at Children's National Medical Center and the chair of the Department of Genomics and Precision Medicine at the George Washington University School of Medicine & Health Sciences in Washington, D.C. Vilain is a fellow of the American College of Medical Genetics, serves on the International Olympic Committee's Medical Commission, and sits on the Board of Scientific Counselors for the National Institute of Child Health and Human Development (NICHD).

References

  1. ↑ Beukeboom, Leo W.; Perrin, Nicolas (2014). The Evolution of Sex Determination. Oxford University Press. p. 158. ISBN   978-0199657148.
  2. ↑ Koob, George F. (2010). Encyclopedia of Behavioral Neuroscience. Elsevier. p. 21. ISBN   978-0080914558.
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  4. 1 2 3 Pandian, T. J. (2013-05-07). Endocrine Sex Differentiation in Fish. CRC Press. doi:10.1201/b14771. ISBN   978-0-429-10222-6.
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  6. ↑ Gilbert, Scott F. (2000). "Chromosomal Sex Determination in Mammals". Developmental Biology. 6th Edition.
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  15. 1 2 3 Pandian, T. J. (2012-06-05). Genetic Sex Differentiation in Fish. CRC Press. doi:10.1201/b12296. ISBN   978-0-429-08641-0.
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  17. ↑ Capel, Blanche (2017-08-14). "Vertebrate sex determination: evolutionary plasticity of a fundamental switch". Nature Reviews Genetics. 18 (11): 675–689. doi:10.1038/nrg.2017.60. ISSN   1471-0056. PMID   28804140. S2CID   4313871.
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  21. ↑ Taborsky, Michael; Schütz, Dolores; Goffinet, Olivier; Doorn, G. Sander van (2018-05-01). "Alternative male morphs solve sperm performance/longevity trade-off in opposite directions". Science Advances. 4 (5): eaap8563. Bibcode:2018SciA....4.8563T. doi:10.1126/sciadv.aap8563. ISSN   2375-2548. PMC   5966226 . PMID   29806019.
  22. ↑ Partridge, Charlyn (2017), "Sneak Copulation as an Alternative Mating Strategy", in Shackelford, Todd K.; Weekes-Shackelford, Viviana A. (eds.), Encyclopedia of Evolutionary Psychological Science, Springer International Publishing, pp. 1–3, doi:10.1007/978-3-319-16999-6_3610-1, ISBN   978-3-319-16999-6
  23. ↑ Oliveira, Rui F. (Rui Filipe Nunes Pais de) (2008). Alternative reproductive tactics an integrative approach. Cambridge University Press. pp. 1–21. ISBN   978-0-521-83243-4. OCLC   850824972.
  24. ↑ Gotthard, Karl; Berger, David; Bergman, Martin; Merilaita, Sami (2009-10-01). "The evolution of alternative morphs: density-dependent determination of larval colour dimorphism in a butterfly". Biological Journal of the Linnean Society. 98 (2): 256–266. doi: 10.1111/j.1095-8312.2009.01290.x . ISSN   0024-4066.
  25. ↑ Fausto-Sterling, Anne; Coll, Cynthia Garcia; Lamarre, Meghan (2012-06-01). "Sexing the baby: Part 1 – What do we really know about sex differentiation in the first three years of life?". Social Science & Medicine. Gender and health: Relational, intersectional, and biosocial approaches. 74 (11): 1684–1692. doi:10.1016/j.socscimed.2011.05.051. ISSN   0277-9536. PMID   21802808.
  26. ↑ Bishop, KATHERINE M.; Wahlsten, DOUGLAS (1997-01-01). "Sex Differences in the Human Corpus Callosum: Myth or Reality?". Neuroscience & Biobehavioral Reviews. 21 (5): 581–601. doi:10.1016/S0149-7634(96)00049-8. ISSN   0149-7634. PMID   9353793. S2CID   9909395.
  27. ↑ Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus (2015-11-30). "Sex beyond the genitalia: The human brain mosaic". Proceedings of the National Academy of Sciences. 112 (50): 15468–15473. Bibcode:2015PNAS..11215468J. doi: 10.1073/pnas.1509654112 . ISSN   0027-8424. PMC   4687544 . PMID   26621705.
  28. ↑ Voigt, Cornelia; Gahr, Manfred (2011-06-08). "Social Status Affects the Degree of Sex Difference in the Songbird Brain". PLOS ONE. 6 (6): e20723. Bibcode:2011PLoSO...620723V. doi: 10.1371/journal.pone.0020723 . ISSN   1932-6203. PMC   3110770 . PMID   21687671.
  29. 1 2 Geary, David C. (2017). "Evolutionary framework for identifying sex- and species-specific vulnerabilities in brain development and functions". Journal of Neuroscience Research. 95 (1–2): 355–361. doi: 10.1002/jnr.23794 . ISSN   1097-4547. PMID   27870407.

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