Sexual differentiation
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224235408
2008-07-07T22:46:11Z
87.1.131.193
/* Psychological and behavioral differentiation */ hominids are extinct, humans excluded
{{otheruses4|the development of sexual dimorphisms in humans|sex differences for all animals|Sexual dimorphism}}
: ''See [[sex differences in humans]] for permanent sex differences.''
'''Sexual differentiation''' is the process of development of the differences between [[male]]s and [[female]]s from an undifferentiated [[zygote]] ([[fertilization|fertilized]] [[ovum|egg]]). As male and female individuals develop from zygotes into [[fetus]]es, into infants, children, adolescents, and eventually into adults, [[sex]] and [[gender]] differences at many levels develop: [[gene]]s, [[chromosome]]s, [[gonad]]s, [[hormone]]s, [[anatomy]], psyche, and social [[behavior]]s.
[[Sex differences]] range from nearly absolute to simply statistical. Sex-dichotomous differences are developments which are wholly characteristic of one sex only. Examples of sex-dichotomous differences include aspects of the sex-specific genital organs such as [[ovary|ovaries]], a [[uterus]] or a phallic [[urethra]]. In contrast, [[sexual dimorphism|sex-dimorphic]] differences are matters of degree (e.g., size of [[Phallus#In physical anatomy|phallus]]). Some of these (e.g., [[height|stature]], behaviors) are mainly statistical, with much overlap between male and female populations.
Nevertheless, even the sex-dichotomous differences are not absolute in the human population, and there are individuals who are exceptions (e.g., males with a uterus, or females with an [[XY sex-determination system|XY]] [[karyotype]]), or who exhibit biological and/or behavioral characteristics of both sexes.
Sex differences may be induced by specific [[genes]], by [[hormones]], by [[anatomy]], or by [[social learning]]. Some of the differences are entirely physical (e.g., presence of a uterus) and some differences are just as obviously purely a matter of social learning and custom (e.g., relative hair length). Many differences, though, such as [[gender identity]], appear to be influenced by both biological and social factors ([[nature versus nurture|"nature" and "nurture"]]).
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 life, a [[fetus]] has no anatomic or hormonal [[sex]], and only a [[karyotype]] distinguishes male from female. Specific genes induce [[gonad]]al 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 [[society|social environment]].
The various ways that genes, hormones, and upbringing affect different human behaviors and mental traits are difficult to test experimentally and charged with political conflict.
==Chromosomal sex differences==
Humans have forty-six chromosomes, including two sex chromosomes, [[XY sex-determination system|XX]] in females and [[XY sex-determination system|XY]] in males. It is obvious that the [[Y chromosome]] must carry at least one essential gene which determines [[testis|testicular]] formation (originally termed ''TDF''). A gene in the sex-determining region of the short arm of the Y, now referred to as ''[[SRY]]'', has been found to direct production of a protein which binds to DNA, inducing differentiation of cells derived from the genital ridges into testes. In transgenic XX mice (and some human [[XX male syndrome|XX male]]s), ''SRY'' alone is sufficient to induce male differentiation.
Investigation of other cases of human sex reversal ([[XX male syndrome|XX male]]s, [[Swyer syndrome|XY female]]s) has led to discovery of other genes crucial to testicular differentiation on [[autosome]]s (e.g., ''WT-1'', ''SOX9'', ''SF-1''), and the short arm of X (''DSS'').
==Timeline==
{|
|+'''Human prenatal sexual differentiation'''
|-
|Fetal age<br>(weeks)
|Crown-rump length<br>(mm)
|Sex differentiating events
|-
|0
|[[blastocyst]]
|Inactivation of one [[X chromosome]]
|-
|4
|2-3
|Development of [[wolffian duct]]s
|-
|5
|7
|Migration of primordial [[germ cell]]s in the undifferentiated [[gonad]]
|-
|6
|10-15
|Development of [[müllerian duct]]s
|-
|7
|13-20
|Differentiation of [[seminiferous tubules]]
|-
|8
|30
|Regression of müllerian ducts in male [[fetus]]
|-
|8
|32-35
|Appearance of [[Leydig cells]]. First synthesis of [[testosterone]]
|-
|9
|43
|Total regression of müllerian ducts. Loss of sensitivity of müllerian ducts in the female fetus
|-
|9
|43
|First meiotic [[prophase]] in [[oogonium|oogonia]]
|-
|10
|43-45
|Beginning of [[virilization|masculinization]] of external [[sex organ|genitalia]]
|-
|10
|50
|Beginning of regression of wolffian ducts in the female fetus
|-
|12
|70
|Fetal [[testicle|testis]] is in the internal [[inguinal ring]]
|-
|12-14
|70-90
|Male penile [[urethra]] is completed
|-
|14
|90
|Appearance of first [[spermatogonium|spermatogonia]]
|-
|16
|100
|Appearance of first [[ovarian follicles]]
|-
|17
|120
|Numerous Leydig cells. Peak of testosterone secretion
|-
|20
|150
|Regression of Leydig cells. Diminished testosterone secretion
|-
|24
|200
|First multilayered ovarian follicles. Canalisation of the vagina
|-
|28
|230
|Cessation of oogonia multiplication
|-
|28
|230
|Descent of testis
|}
*Reference: [http://www.gfmer.ch/Books/Reproductive_health/Human_sexual_differentiation_Table1.html PC Sizonenko] in ''Pediatric Endocrinology'', edited by J. Bertrand, R. Rappaport, and PC Sizonenko, (Baltimore: Williams & Wilkins, 1993), pp. 88-99.
==Gonadal differentiation==
Early in fetal life, [[germ cell]]s migrate from structures known as yolk sacs to the [[Gonadal ridge|genital ridge]]. By week 6, undifferentiated [[gonad]]s consist of [[germ cell]]s, supporting cells, and steroidogenic cells.
In a male, ''SRY'' and other genes induce differentiation of supporting cells into [[Sertoli cell]]s and (indirectly) steroidogenic cells into [[Leydig cell]]s to form [[testis|testes]], which become microscopically identifiable and begin to produce hormones by week 8. Germ cells become [[Spermatogonium|spermatogonia]].
Without ''SRY'', [[ovary|ovaries]] form during months 2-6. Failure of ovarian development in 45,X girls ([[Turner syndrome]]) implies that two functional copies of several [[X chromosome|Xp]] and [[X chromosome|Xq]] genes are needed. Germ cells become [[ovarian follicle]]s. Supporting and steroidogenic cells become [[theca cell]]s and [[granulosa cell]]s, respectively.
==Hormonal differentiation==
In a male fetus, testes produce [[steroid hormone|steroid]] and protein [[hormones]] essential for internal and external anatomic differentiation. [[Leydig cell]]s begin to make [[testosterone]] by the end of month 2 of gestation. From then on, male fetuses have higher levels of [[androgen]]s in their systemic blood than females. The difference is even greater in pelvic and genital tissues. [[Antimullerian hormone]] (AMH) is a protein hormone produced by [[Sertoli cell]]s from the 8th week on. AMH suppresses development of [[müllerian ducts]] in males, preventing development of a [[uterus]].
Fetal ovaries produce [[estradiol]], which supports follicular maturation but plays little part in other aspects of prenatal sexual differentiation, as maternal estrogen floods fetuses of both sexes.
==Genital differentiation==
{{Main|Development of the urinary and reproductive organs}}
A differentiation of the [[sex organ]] can be seen. However, this is only the external genital differentiation. There is also an internal genital differentiation.
===Internal genital differentiation===
[[Gonad]]s are histologically distinguishable by 6-8 weeks of gestation. A fetus of that age has both mesonephric ([[wolffian ducts|wolffian]]) and paramesonephric ([[mullerian ducts|mullerian]]) ducts. Subsequent development of one set and degeneration of the other depends on the presence or absence of two testicular hormones: [[testosterone]] and [[antimullerian hormone|AMH]]. Disruption of typical development may result in the development of both, or neither, duct system, which may produce morphologically [[intersexual]] individuals.
Local testosterone causes each wolffian duct to develop into [[epididymis]], [[vas deferens]], and [[seminal vesicles]]. Without male testosterone levels, wolffian ducts degenerate and disappear. Müllerian ducts develop into a [[uterus]], [[fallopian tube]]s, and upper [[vagina]] unless AMH induces degeneration. The presence of a uterus is stronger evidence of absence of testes than the state of the external [[genitalia]].
===External genital differentiation===
''For illustrations, see the [[#External links|External links]] section.''
By 7 weeks, a fetus has a [[genital tubercle]], [[urogenital groove]] and sinus, and [[labioscrotal folds]]. In females, without excess androgens, these become the [[clitoris]], [[urethra]] and [[vagina]], and [[labia (genitalia)|labia]].
Males become externally distinct between 8 and 12 weeks, as androgens enlarge the phallus and cause the urogenital groove and sinus to fuse in the midline, producing an unambiguous [[penis]] with a phallic urethra, and a thinned, rugated [[scrotum]].
A sufficient amount of any androgen can cause external [[virilization|masculinization]]. The most potent is [[dihydrotestosterone]] (DHT), generated from testosterone in skin and genital tissue by the action of 5α-reductase. A male fetus may be incompletely masculinized if this enzyme is [[5-alpha-reductase deficiency|deficient]]. In some [[disease]]s and circumstances, other androgens may be present in high enough concentrations to cause partial or (rarely) complete masculinization of the external genitalia of a genetically female fetus.
Further sex differentiation of the external genitalia occurs at [[puberty]], when androgen levels again become disparate. Male levels of testosterone directly induce growth of the penis, and indirectly (via DHT) the [[prostate]].
==Breast differentiation==
Visible differentiation occurs at [[puberty]], when [[estradiol]] and other hormones cause [[breast]]s to develop in girls. However, fetal or neonatal androgens may modulate later breast development by reducing the capacity of breast tissue to respond to later [[estrogen]].
==Hair differentiation==
The amount and distribution of body [[hair]] differs between the sexes. Males have more [[terminal hair]], especially on the [[facial hair|face]], [[chest hair|chest]], [[abdominal hair|abdomen]] and back, and females have more [[vellus hair]], which is less visible. This may also be linked to [[neoteny]] in humans, as [[vellus hair]] is a [[adolescent|juvenile]] characteristic.
==Other body differentiation==
The differentiation of other parts of the body than the [[sex organ]] creates the [[secondary sex characteristic]]s.
General habitus and shape of body and face, as well as [[sex hormone]] levels, are similar in prepubertal boys and girls. As puberty progresses and sex hormone levels rise, obvious differences appear.
In males, testosterone directly increases size and mass of muscles, [[vocal cords]], and [[bone]]s, enhancing strength, deepening the voice, and changing the shape of the face and skeleton. Converted into DHT in the skin, it accelerates growth of androgen-responsive facial and body hair. Taller stature is largely a result of later puberty and slower [[epiphyses|epiphyseal fusion]].
In females, in addition to breast differentiation, estrogen also widens the [[pelvis]] and increases the amount of body [[fat]] in hips, thighs, buttocks, and breasts. Estrogen also induces growth of the uterus, proliferation of the [[endometrium]], and [[menstrual cycle|menses]].
The difference in adult masculine and feminine faces is largely a result of heavier jaw and jaw muscle development induced by testosterone in late adolescence. Masculine features on average are slightly thicker and coarser. Androgen-induced recession of the male hairline accentuates these differences by middle adult life.
Sexual dimorphism of skeletal structure develops during childhood, and becomes more pronounced at adolescence. Sexual orientation has been demonstrated to correlate with skeletal characters that become dimorphic during early childhood (such as arm length to stature ratio) but not with characters that become dimorphic during puberty (such as shoulder width) (Martin & Nguyen, 2004).
==Brain differentiation==
In most animals, differences of exposure of a fetal or infant [[brain]] to sex hormones produce significant and irreversible differences of brain structure and function which correlate with adult reproductive behavior.
This seems to be the case in humans as well; sex hormone levels in male and female fetuses and infants differ, and both [[androgen receptors]] and [[estrogen receptors]] have been identified in brains. Several sex-specific genes not dependent on sex steroids are expressed differently in male and female human brains. Structural sex differences begin to be recognizable by 2 years of age, and in adult men and women include size and shape of [[corpus callosum]] and certain [[hypothalamus|hypothalamic]] nuclei, and the [[gonadotropin]] feedback response to [[estradiol]].
==Psychological and behavioral differentiation==
Human adults and children show many psychological and behavioral sex differences, both dichotomous and dimorphic. Some (e.g., dress) are learned and obviously cultural. Others are demonstrable across cultures and may have both biological and learned determinants. For example, girls are, on average, more verbally fluent than boys, but males, on average, are better at spatial calculation. Because we cannot explore hormonal influences on human behavior experimentally, and because potential political implications are so unwelcome to many factions of society, the relative contributions of biological factors and learning to human psychological and behavioral sex differences (especially gender identity, role, and [[sexual orientation|orientation]]) remain unsettled and controversial.
Current theories of mechanisms of sexual differentiation of brain and behaviors in humans are based primarily on three sources of evidence: animal research involving manipulation of hormones in early life, observation of outcomes of small numbers of individuals with disorders of sexual development ([[intersex]] conditions or cases of early [[sex reassignment]]), and statistical distribution of traits in populations (e.g., rates of homosexuality in twins). Many of these cases suggest some genetic or hormonal effect on sex differentiation of behavior and mental traits<ref>[[Steven Pinker|Pinker, Steven]]. [[The Blank Slate]]. New York: Penguin. 2002. pages 346-350</ref>; others do not{{Fact|date=March 2007}}.
In addition to affecting development, changing hormone levels affect certain behaviors or traits that are gender dimorphic, such as superior verbal fluency among women.<ref>[[Steven Pinker|Pinker, Steven]]. [[The Blank Slate]]. New York: Penguin. 2002. pages 347-348</ref>.
In most [[mammal]]ian species females are more oriented toward child rearing and males toward competition with other males.
===Biology of gender===
{{Main|Biology of gender}}
Biology of gender is the scientific analysis of the physical basis for behavioural differences between men and women. It deals with [[gender identity]], [[gender roles]] and [[sexual orientation]].
==Defeminization and masculinization==
{{Main|Defeminization and masculinization}}
'''[[Defeminization]] and [[masculinization]]''' are the differentiating processes that a fetus goes through to become male. From this perspective, the female is the default path for a developing human being in that gene actions that are eliminated and that are necessary for formation of male genitalia lead to the development of external female genitalia.
Biologically, this perspective is supported by the fact that there are neither female genes nor female hormones that correspond to the hormones active in males only. Estrogen, for instance, is present in both the male and female fetus.
==See also==
* [[Virilization]]
* [[Sexual dimorphism]]
* [[Sex differences in humans]]
* [[List of homologues of the human reproductive system]]
* [[gender]]
*[[Sex-determination system]]
**[[XY sex-determination system]]
**[[X0 sex-determination system]]
**[[ZW sex-determination system]]
**[[Haplo-diploid sex-determination system]]
* [[Fetal genital development]]
==References==
{{Reflist}}
* Baum MJ. Mammalian animal models of psychosexual differentiation: When is
‘translation’ to the human situation possible? (2007)Hormones and Behavior 50:579–88.
* Crouch RA. Betwixt and between: the past and future of intersexuality. J Clin Ethics 9:372-384.
Hughes IA, Houk C, Ahmed SF, Lee PA, LWPES/ESPE Consensus Group. (2006) Consensus statement on management of intersex disorders. Arch Dis Childhood.
* Martin, J. T. and Nguyen, D. H. (2004). Anthropometric analysis of homosexuals and heterosexuals: implications for early hormone exposure. Hormones and Behavior 45. 31-39.
* Phoenix, C.H., Goy, R.W., Gerall, A.A. and Young, W.C. (1978). Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65, 369-382.
* Wallen, K. (2005) Hormonal influences on sexually differentiated behavior in nonhuman primates. Frontiers in Neuroendocrinology 26, 7-26.
* Wilson BE, Reiner WE. (1998) Management of intersex: a changing paradigm. J Clin Ethics 9:360-9.
==External links==
* [http://www.gfmer.ch/Books/Reproductive_health/Human_sexual_differentiation.html Human Sexual Differentiation] by P. C. Sizonenko
* [http://www.the-clitoris.com/n_html/n_netter.htm The Ciba Collection of Medical Illustrations: Vol.2, Reproductive System] by Frank H. Netter, M.D. comparing female and male reproductive systems development and anatomy
* [http://www.the-clitoris.com/n_html/n_develop.htm Development of the Female Sexual & Reproductive Organs] – illustrations comparing female and male genitalia during the early development
{{Reproductive physiology}}
[[Category:Biology of gender]]
[[Category:Gender]]
[[Category:Sex]]
[[de:Geschlechtsdetermination]]