whether ovaries or testes develop from an indifferent gonad
defined by the XX or XY
is not necessarily identical with the phenotypic sex seen later in life
development of female or male structures
what someone considers to be their sex
Where do indifferent (non-determined) gonads develop from?
the primitive gonadal streak on the genital ridge
which is a condensation of tissue near the adrenal gland
From which part of the the indifferent gonad do ovaries develop? Testes?
Ovaries develop from the Cortex
Testes develop from the Medulla
both do so at week 6 of embryonic/fetal development
the non-differentiating portion of the primitive gonad regresses as the other develops
What kind of hormones do embryonic ovaries produce vs. embryonic testes?
embryonic ovaries do NOT produce estrogens
while embryonic testes produce testosterone
& MIF to control further masculinization
What is the small amount of information that initiates the differences between a male & female?
the SRY Gene (Sex-determining Region of the Y chromosome) which when transcribed results in the Testis-determining factor (TDF) [also known as Sex-determining region Y (SRY) protein]
What does translocation of SRY to X chromosome results in?
a male with XX karyotype
b/c the majority of genetic information on the Y chromosome is common to females
Testis-determining factor (TDF)
initiation of male sex determination in humans by initiating the transcription of several genes necessary for development of male characteristics in the embryo including testicular differentiation & formation of the internal male structures under the influence of Muellerian Inhibiting Substance (MIS)
TDF → causes the medulla portion of the indifferent gonad to differentiate → testis → which secrete testosterone & MIS
In the newly developing testes, what hormone do Sertoli cells secrete?
Müllerian Inhibiting Factor (MIF) also known as Anti-Müllerian Hormone (AMH)
Müllerian Inhibiting Factor (MIF)
causes regression of the Müllerian duct (the female duct system, which if allowed would go on to form the uterus, fallopian tubes, & upper parts of vagina)
In the newly developing testes, what hormone do Leydig cells secrete?
promotes development of the vas deferens, epididymous, & other Wolffian duct derivatives (Wolffian = the male duct system)
made by 5α-reductase in the testis & some local tissues from testosterone
it induces the formation of the external genitalia & male secondary sex characteristics (penis, urethra, prostate)
acts via the same receptor as testosterone, but has a much higher potency due to a ~50 fold increase in binding efficiency for the receptor
it cannot be aromatized into estrogens (in contrast to testosterone)
What is DHT responsible for later in male life?
it potentiates the development of acne & male pattern baldness
in genetic females the cortex of the indifferent gonad differentiates into the ovary
the embryonic ovary secretes no estrogen
b/c in female development no testosterone is synthesized/secreted, the Wolffian duct won't develop therefore by default the Müllerian duct develops into all those aforementioned female structures
also the labia minora develops first - he mentioned that a few times incase it becomes important
When might one be able to visibly differentiate between male and female genitalia in the womb?
17 weeks for males
~20 weeks for females (internal)
preterm females tend to have a more developed clitoris than other structures (eg. labia minora)
What is a significant cause of abnormally developed external somatic sex, aka having ambiguous (incompletely correct) male or female genitalia?
affected individuals are externally phenotypically female but have rudimentary or absent gonads, short stature, & mild obesity w/ a characteristic nuchal fat pad of variable prominence
these women undergo no sexual maturation at
puberty, but this can be treated with hormonal supplementation
they have normal intelligence but may have other congenital anomalies
Klinefelter’s Syndrome (XXY)
affected individuals have male genitalia but abnormal seminiferous tubules such that they are sterile
these men have an increased incidence of mental retardation
seminiferous tubule dysgenesis (abnormal embryonic organ development)
Female Developmental Disorders
• Iatrogenic (exposure to androgen, progestational agents during pregnancy)
• Congenital virilizing adrenal hyperplasia of the fetus (21 hydroxylase deficiency)
Male Developmental Disorders
• Androgen resistance
• Defective testicular development
• Congenital virilizing hyperplasia of the fetus
Congenital Virilizing Adrenal Hyperplasia
caused by a defect in an enzyme involved the glucocorticoid or mineralocorticoid synthesis pathways, resulting in an overproduction of androgenic steroids & a lack of glucocorticoid &/or mineralocorticoids
depending on the enzyme involved & the degree of lack of activity, this condition may present a life-threatening condition a few days after birth (males will present in shock - steroid crisis)
when endocrine & gametogenic functions of gonads are able to allow reproduction
there is initiation & continuation of changes in external sexual & internal reproductive structures for reproductive capacity
has a variable onset (the average age of which has been decreasing for > 175 years)
What are the average ages of onset for male & female puberty in the U.S.?
males: 9-10 y/o
females 7 - 8 (African American) or 8 - 9
a delayed puberty workup is called for at age 13 in females if there is a lack of menses onset & age 14 in males if there's absent testicular development
Stages in Male Puberty
2. testicular enlargement begins
3. penile enlargement
4. growth of the glans penis
5. completion into the appearance of adult
also corresponds w/ the development of male pubic hair pattern (escutcheon) & laryngeal enlargement & increased rigidity (deeper voice)
What does the hypothalamic- pituitary-gonadal axis control in males?
1. spermatogenesis in seminiferous tubules of testes
2. androgen biosynthesis in Leydig cells of the testes
When do plasma testosterone levels in males max out?
at around 26-27 years of age
Actions of Androgens
bind to androgen receptors target tissues
are required for normal sperm maturation, normal function of sex accessory glands (epididymis, seminal vesicles, prostate, & bulbourethral gland), the maintenance of male secondary sex characteristics, & are particularly important for regulating prostate size (benign prostatic hyperplasia (BPH))
What is the order of androgen potency (MOST → least)?
DHT → testosterone → androstenedione → DHEA
Stages in Female Puberty
1. Thelarche (breast development)
2. Pubarche (development of female pubic
3. Menarche (onset of menstruation)
How can menstrual periods initially be described?
Variable in length
Irregular in cycle
What's the difference between male stages of puberty & female?
the general stages of male puberty don't have to proceed in order whereas the female stages of puberty DO
In the beginning of female puberty, when & how is Gonadotropin Releasing Hormone (GnRH) released from the hypothalamus?
it's released in a pulsatile manner the levels of which tend to peak at night & drop during the day for the start of puberty
Unlike in men, how do levels of gonadotropins in females change throughout a lifetime?
as women age, GnRH, FSH, & LH increase (estrogen drops off after menopause though)
the early development of secondary sexual
characteristics without gametogenesis (aka (no spermatogenesis or ovarian development) caused by abnormal exposure of immature males to androgen or females to estrogen
True Precocious Puberty
early but otherwise normal pubertal pattern of gonadotropin secretion from the pituitary
can be constitutional, cerebral (posterior hypothalamic disorders), caused by tumors, infections, gonadotropin-independent precocity, or developmental abnormalities
Constitutional Precocious Puberty
precocious puberty with no underlying
is more common in females than in males
Fertilization in Humans
normally occurs in ampulla of the Fallopian tube
sperm has chemoattraction to the ovum & adheres to the Zona Pellucida
the acrosomal reaction (breakdown of the acrosome) occurs, releasing proteases (eg. acrosin) that facilitate penetration
fertilin mediates fusion to ovum membrane, & once fused, development starts & polyspermia is prevented
Changes in the Endometrium & Blastocyst in Preparing For Implantation
before the embryo implants into the endometrium it receives nourishment from the uterine secretions: steroid dependent proteins, cholesterol, steroids, iron, & fat-soluble vitamins.
glandular epithelium synthesizes matrix substances, adhesion molecules, & surface receptors for matrix proteins, all needed for implantation
the blastocyst secretes Human Chorionic Gonadotropin (hCG) & other substances required for implantation
Human Chorionic Gonadotropin (hCG)
secreted by the blastocyst & acts as an immunosuppressive agent, has growth- promoting activity, as well as acts like an autocrine growth factor that promotes placental development
forms when the blastocyst comes into contact with the uterine endometrium & surrounds the blastocyst
it erodes the uterine endometrium, allowing the blastocyst to implant
establishes the nutrient circulation between the embryo and the mother, establishing an interface between maternal blood & embryonic extracellular fluid, facilitating passive exchange of material between the mother and the embryo
What are the important functions of a placenta?
1. hormone production
2. gas transport & exchange (O2, CO2)
3. solute transport
4. storage of proteins, glycogen, iron, etc.
5. control of molecular passage (IgG is the only Ab that can cross the placenta)
What hormones are made by the placenta?
human chorionic gonadotropin (hCG)
human chorionic somatomammotropins (hCS1/ hCS2, or placental lactogens)
peptide hormones + neuropeptides
placental variants of all known hypothalamic
refers to the fact that these 3 are metabolically & hormonally interconnected
the placenta produces estrogen & progesterone for maintaining pregnancy health + pregnenalone for fetal steroid synthesis
the mother supplies energy substrates for the fetus & cholesterol for placental pregnenalone synthesis
the placenta metabolizes maternal steroids
the fetus makes DHEAS (dehydroepiandrosterone sulfate) which is transferred back to the placenta for estrogen (estriol, estradiol) synthesis
the fetus also synthesizes, cortisol, cortisone, & other needed hormones, & locally changes sulfated steroids to useful forms
Placental Hormone Synthesis
b/c the mother cannot synthesize all hormones needed to support a pregnancy herself, the placenta is a significant supplier of progesterone & estrogens to help support the pregnancy
HOWEVER the mother supplies the placenta w LDL cholesterol as the placenta alone can't make enough cholesterol to support steroid synthesis
AND the placenta lacks hormones necessary for steroid synthesis - help comes from the fetus
Which hormones does the placenta lack and where in the fetus do they come from in the conversion of precursors to steroid hormones?
planenta lacks 17α-hydroxylase & 17,20-desmolase for estrone & estradiol synthesis
the placenta also lacks 16α-hydroxylase for estriol synthesis
all the conversions can be made by the aforementioned enzymes found in the fetal adrenal gland & liver
Response of the Mother to Pregnancy
↑ blood volume & cardiac output
↑ alveolar ventilation
↑ weight gain
↑ demand for dietary protein, iron, & folic acid supplements are recommended
recommended weight gain is in the range of 11.5-16 kg for most women (5 kg for intrauterine contents, 9 kg maternal contribution)