Psyc 370 Sexual Development

Definition of Intersex:

"A general term used for a variety of conditions in which a person is born with a reproductive or sexual anatomy that doesn't seem to fit the typical definitions of male or female."

Gender Dysphoria (GD)

"A marked incongruence between one's experienced/expressed gender and assigned gender," A CNS-limited form of Intersexuality?

The stages of anatomical sexual development (10-13 yrs)

(Puberty) Secondary Sex Characteristics: Breasts, shoulders, hips, body hair

Making a man: Step 1

1. Genes: XY, Gene on Y produces Sry protein signals the primordial gonads

The stages of anatomical sexual development (12 wks)

12 weeks: Ductwork, Wolfian (male): Vas Deferens, Seminal Vesicles, Mullarian (female): Fallopian Tubes, Uterus

Making a woman: Step 2

2. (6 wks) Gonads: Cortex develops into ovary

Making a man: Step 2

2. (6 wks) Primordial Gonads Medulla matures into testes, Fetus: 11 cm (shrimp), Sry protein--> Medulla

Making a woman: Step 3

3. (12 weeks) Absence of Testosterone causes Ductwork to mature into Fallopian tubes, uterus, and upper portion of vagina, In the Absence of testes (and thus absence of testosterone & Mullerian inhibiting substance), the Mullerian system develops & Wolffian system deteriorates

Making a man: Step 3

3. (12 weeks) Testosterone causes Ductwork to mature into seminal vesicle & vas deferens, Testes secrets testosterone, Testosterone causes Wolfian system to develop into seminal vesicle and vas deferens and testes to descend, Testes also secrete Mullerian-inhibiting substance--> causes Mullarian system to deteriorate

Making a woman: Step 4

4. (8 weeks) External reproductive organs (clitoris, labia) begin to develop, Lack of testes/ testosterone means that the bipotential precursor will develop into female external genitals, 12-15 weeks: sonogram can detect sex

Making a man: Step 4

4. (8 weeks) External reproductive organs (penis and scrotum) begin to develop, Testes produce a surge of testosterone which causes the bipotential precursor to morph into a penis and scrotum, At 12-15 weeks you can see sex differences on sonogram

The stages of anatomical sexual development (8-15 wks)

8-15 weeks: Bipotential Precursor--> Primary sex characteristics (external genitals), Penis/Scrotum or Labia, Clitoris, *Brains also begin to develop sex differences at 8 wks

Congenital Adrenal Hyperplasia (CAH) XX or XY Cause:

Abnormal synthesis of corticosteroids leading to increased exposure to androgens late prenatally and postnatally

Sexual development and gender identity conclusion: Hormones

Almost certainly due to prenatal hormone environment

Trans man:

Anatomically F, but M gender identity

Trans woman:

Anatomically M, but F gender identity

What affects gender identity during fetal development?: Maternal use of drugs

Anticonvulsant drugs: Phenobarbital/diphantoin, Synthetic estrogens: Diethylstilbestrol (DES)

Mechanisms for Intersex: XY (male looks female) Early/Genetic Phase:

At 6 weeks, if the Y chromosome fails to produce SRY protein, Ovaries would develop instead of testes, Genotype XY, but Phenotype XX, "Streak" Ovaries- non-functional, Ductwork: Uterus, vagina, fallopian tubes, Primary sex char: Labia, Clitoris

Sexual development and gender identity conclusion: Genes

Best bet is on androgen receptors

Hormones affecting development: Mid pregnancy (late 2nd trimester - 3rd trimester)

Brain differentiation?

Typical brain-hormone connection

Brain--> hormone--> target: organs/tissues, Brain--> hormone--> endocrine gland--> hormone--> organs/tissues

Berthold (1849)

Castrated roosters, found that they no longer engaged in sex-stereotyped behavior (e.g., crow, approach females, act aggressively), Berthold concluded that a chemical produced by the testes and released into the circulatory system influenced sex-stereotyped behavior

Making a man/woman: Step 5

Caused by a cascade of hormones from the HPA axis, Development of Secondary Sex Characteristics: Body hair, breast & penis development

Hormone:

Chemical messenger produced by a gland that is carried by the circulatory system to a distant target organ, Produced in various regions of the brain (e.g., hypothalamus, pituitary) and adrenal glands, gonads (testes, ovaries), Targets: Mammary glands, muscle Tissue, brain

Steroid Hormones

Cholesterol is the common precursor, Brain: Hypothalamus, Pituitary produce Releasing/stimulating hormones, Adrenal Cortex hormones: Cortisol, corticosterone etc, Progesterone Gonadal Hormones: Estrogens (e.g., estradiol), Testosterone

Miscoded Somatosensory map Evidence (Ramachandron and McGeouch, 2007)

Cisgender men/women who have penilectomy/mastectomy often report phantom penises/breasts, Transwomen (penilectomy) usually do not report phantom penises and Transmen (mastectomy) don't report phantom breasts. Compared: 8 Transmen to 8 Cisgender women, Functional imaging (MEG, DTI), Compared physical stimulation (tapping) of hand and breast, No difference between groups in brain response to hand tapping

The stages of anatomical sexual development (conception-6 wks)

Conception: XX, XY, 6 wks: Primordial gonads--> ovaries/testes

Hormones affecting development: Puberty

Development of secondary sex characteristics and activation of interest in sexual activity

Hormones Organizing effects

Expression of primary and secondary sex differences, Conception, pregnancy, lactation, Sexual differentiation of the brain, Muscle development, Self-regulated behaviors

Turner Syndrome (XO) Ductwork:

Fallopian Tubes, Uterus

Treatment Processes: M to F

Feminizing hormone treatments: antiandrogen and oestrogen, Hair removal, Surgery: orchidectomy, penectomy, labioplasty, clitoroplasty, vaginoplasty, breast augmentation, facial plastic surgery, thyroid chondroplasty

What affects gender identity during fetal development?: Other

Fraternal birth order effects

Miscoded Somatosensory map

Gender could be/probably is included in the somatosensory homunculus, Theory: Transgender map not aligned with phenotype

Sexual development

Genes (Y chromosome) releases protein or not--> Ovaries/Testes, Ovaries/testes--> hormones--> Target in peripheral tissues--> sexual anatomy OR Target in brain--> anatomy AND gender identity

Congenital Adrenal Hyperplasia (CAH) XX or XY Ductwork:

Genetically concordant

Congenital Adrenal Hyperplasia (CAH) XX or XY Gonads:

Genetically concordant

Body:

Gonads, ovaries and testes

Anatomical sexual characteristics from birth until puberty

Gonads: Ovaries, Testes, Ducts: XX- Uterus, vagina, fallopian tubes, XY- seminal vesicles, vas deferens, External Reproductive organs: not well developed (Labia/Clitoris or Penis/Scrotum), Secondary Sex Characteristics: Not present

(Puberty) Anterior Pituitary-->

Growth Hormone--> bones/muscle--> Growth Spurt

Hormones: The other chemical messenger

Hormones are partially or wholly responsible for the following behaviors/characteristics/processes, Anatomical differences and developmental changes, activating effects and organizing effects

Sexual development and gender identity conclusion: Brain

Hypothalamus probably plays a role, Somatosensory cortex may play a role

Brain (CNS):

Hypothalamus, Amygdala, pre-optic regions

Mechanisms for Intersex XX (female looks male) Early Development:

If a XX fetus is exposed to testosterone after 6 weeks, Ovaries, Genotype XX, but Phenotype XY, Combination of ductwork, T--> Seminal Vesicles, Vas Deferens, Absence of MIS--> fallopian tubes, uterus, vagina, Scrotum, Penis

Mechanisms for Intersex XX Ductwork Phase:

If an XX fetus is exposed to testosterone between 8-15 weeks, Ovaries, Genotype XX, Phenotype ambiguous to XY, Ductwork: Uterus, and Fallopian tubes, BP will develop along male lines—Enlarged clitoris to penis

A Behavioral Neuroscience Hypothesis Transgenderism Working Hypothesis

If intersex conditions are caused by sex hormone abnormalities that occur early in development that affect the development of anatomy (gonads/sex organs) THEN it seems likely that transgender development is caused by sex hormone abnormalities that occur later in development and/or only affect the development of sex differences in the brain, Strongest evidence for the role of the hypothalamus

Mechanisms for Intersex: XY Ductwork Phase I:

If testicles failed to develop=NO Testosterone (T) or Mullerian Inhibiting Substance (MIS) Nonfunctional Testes, Genotype XY, but Phenotype XX, Ductwork: Uterus, vagina, fallopian tubes, Primary Sex Char: Labia, Clitoris

Hormones affecting development: Post natal period

In first few weeks post-partum, a surge of T for boys

What causes someone to be intersex?

Intersex development is caused by a mis-step in the stages of pre-natal sexual development, Important issues: The earlier in the process, the more profound the anatomical effects, The relationship between intersex and gender identity is complex

Turner Syndrome (XO) External Sex Characteristics:

Labia, Vagina, Secondary sex characteristics. At puberty, the lack of functioning ovaries disrupt pubertal development, primary amenorrhoea (no menstration), infertility. However, oocyte donation can make pregnancy possible.

Congenital Adrenal Hyperplasia (CAH) XX or XY External Sex Characteristics:

Male: Typical, Female: Masculinized external genitals (enlarged clitoris, partially fused labia), Secondary sex characteristics develop typically with hormone therapy

Treatment Processes: F to M

Masculinizing hormone treatment: testosterone, Surgery: mastectomy, oophorectomy, hysterectomy, vaginextomy, medoidioplasty or phalloplasty, scrotoplasty, urethroplasty, testicular prostheses

Caster Semenya

Middle distance runner (800 meters) for South Africa. Following her victory at the 2009 World Championships, some questioned whether she was indeed a woman. Caster was subjected to sex testing. She was withdrawn from international competition until 2010 when the IAAF cleared her to return to competition. Details of her medical history were leaked to the press, something that she reports to have been humiliating. Internal testes, Shallow vagina, Hyperandrogenic (HA)

Treatments (continued)

Most trans people satisfied with surgical/medical procedures, M to F: 87%, F to M: 97% (in 1990)

Transgender

No definitive explanation about what causes people to have a gender identity different from their anatomical sex. Theories: Social environments, Personal Choice, Biologically determined: Prevailing theory is that prenatal hormonal environment can produce changes in the brain independently of changes that affect development of anatomical differences.

Turner Syndrome (XO) Gonads:

Ovaries (but may be comprised of fibrous, non functional tissue)

Olympic sports physical examination

Pee-test, 1950s - 1996: chromosome testing, Late 1990s - now: hormone tests

Non-hormonally caused conditions that affect primary sex characteristics (XY) Ablatio penis:

Penis accidentally damaged during circumcision, Surgically altered to create female phenotype, Stats hard to come by

Hormones affecting development: 6-15 weeks

Physiological development of anatomical sex characteristics, Gonads, ductwork, external sex characteristics

What affects gender identity during fetal development?: Genetic

Polymorphisms in Estrogen receptor (ER A and B), androgen receptors, aromatase genes, Aromatase is the enzyme that converts androgens to estrogens, Some of these are on the X chromosome, Epigenetics: The key factor may be when/whether/where genes for receptors are turned on

Hormones affecting development post-natally:

Post natal Rhesus monkeys-neonatal castration produced no changes in sex-stereotyped behavior

Hormones affecting development post-natally: Conclusion

Postnatal changes in hormonal environment does not appear to have a marked effect on gender identity or at least gender stereotyped activity

Neurotransmitter:

Produced in a neuron/nerve, Targets: Dendritic receptors in brain, other organs, muscle tissue

Hypothalamus during puberty:

Releases Gonadotropin releasing hormones (GnRH), Ovaries/Testes--> Androgens, Estrogens, Important to note that both males and females have both androgens and estrogens, Balance determines the direction of development, "male" vs. "female" sex hormones play important roles in the development of both sexes

Hypothalamus:

Releasing Factor (RF)

Transgender

Reproductive anatomical features are consistent with typical male/female lines, Gender identity is discordant with anatomy, DSM V: Gender Dysphoria (GD)

Behavior (targets):

Reproductive system, Structures associated with secondary sex characteristics

Making a woman: Step 1

Same as man, w/o testosterone 1. Genes: XX, No Y, no Sry,

"True sex policy":

Sex should be determined by the "key biological criterion of sex," Pre 19th century: External genitalia, Late 19th century: Gonadal histology (do you have testicles or ovaries?), Mid 20th century: Genotype

How to describe AIS person

Sex: Male, Gender: Male, Gender identity: Almost (?) always female, Gender roles: , Sexual orientation:

Hormones Activating effects

Sexual behavior, Eating, drinking, voiding, Sleeping, Emotions

There are observed differences between transgender/cisgender

Sexual dimorphic nucleus (SDN)/Preoptic Area (POA), Central subdivision of the Bed nucleus of the strai terminalis (cBST), Interstitial Nuclei of the Anterior Hypothalamus (INAH)

What do we know about sex differences in the brain?

Sexual dimorphisms in adult brains were found in brain regions that have high sex hormone receptor density during early development, Differences in brain volume, F>M: Frontal, paralimbic areas, M>F: Frontomedial cortex, hypothalamus, amygdala, angular gyrus

Intersex

Someone who has reproductive anatomical features that are inconsistent with genetic sex, or don't fit the typical definitions of male or female, May or may not have GD

Congenital Adrenal Hyperplasia (CAH) XX or XY Gender identity:

Somewhat higher incidence of transgender in females

Intersex development

Stages of prenatal sexual development coincide with prenatal surges of Testosterone, First 12 weeks: XY, Gonads, Ductwork, External genitals, Hypothalamus development, Second half of pregnancy: Further sexual differentiation of brain development, Puberty (both estrogens and androgens), Secondary sex characteristics (puberty), Take home: Because brain and body develop at different stages of pregnancy, they are subject to disconnection

Pituitary:

Stimulating Hormones (SH)

Behavioral Endocrinology

Study of the relationship between hormones and the nervous system

Mechanisms for Intersex: XY Ductwork Phase II:

Testicles release T, but ductwork/precursor are Non-responsive to T, Internal Testes: T and MIS secreted, Genotype XY, XX phenotype, Ductwork non responsive to T: No Vas Deferens or seminal vesicles and testes don't descend, Mullarian Inhibiting substance--> No Uterus or fallopian tubes, BP non responsive to T--> Development of Labia, Clitoris

Hormones affecting development post-natally: Older age

Testosterone suppression or gonadectomy in men with prostate cancer produces no change in gender identity

Transition

The process of changing from living from one's phenotypic gender to living congruently with one's gender identity, Transition may or MAY NOT involve treatment/surgery

Miscoded Somatosensory map evidence: Breast tapping

Transmen (compared to cisgender W): Reduced activation in one region of the somatosensory cortex (supramarginal gyrus) and secondary somatosensory cortex . Heightened activation in medial temporal lobe. Supramaginal gyrus is part of the somatosensory cortex and plays a role in perception of body in space, Diminished activation in these regions may explain why breasts don't feel like "self" for transmen

Hyperandrogenism (HA)

Typical female range: 0.12 to 1.79 nmol/L, Typical male ranges: 7.7 and 29.5 nmol/L

Turner Syndrome (XO) Gender identity:

Typically female

Turner Syndrome (XO) Genetics:

XO or X (dysfunctional X)

Congenital Adrenal Hyperplasia (CAH) XX or XY Genetics:

XX or XY

Non-hormonally caused conditions that affect primary sex characteristics (XY) Cloacal exstrophy:

XY born with malformations of bladder, intestines, and penis (penis may be absent). (Historically) surgically altered to create female phenotype, 35-53% gender dysphoric to transgender

(Puberty) Adrenal cortex-->

androgens, Pubic and axillary hair

Significant thalamic/hypothalamic development begins

late in the first trimester and continues through the second trimester

There are notable sex differences between

men and women in the hypothalamus

Hypothalamus and Pituitary are part of the

midbrain and produce hormones that control metabolism, and the 4 Fs.

Anatomical sex does

not always match sex chromosomes

You make a woman by

not making a man, Female is the default gender, Females develop in the ABSENCE of testosterone

Brain-Body Connection: Sex hormones

slide 7

People are assigned a gender based on

the appearance of their external genitals when they are born

Development of anatomical sex is complex and

there are many ways for otherwise healthy people to have anatomical features that are not consistent with their genetic sex.

The defining feature of hormone v. neurotransmitter is in how

they are released and the type of that are receptors activated

Development of sex organs is done by

~ 15 weeks