Physio Intro Reproductive Physio (21)

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

• the primitive gonadal streak on the genital ridge
• which is a condensation of tissue near the adrenal gland
• 

• 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

• embryonic ovaries do NOT produce estrogens
• while embryonic testes produce testosterone
• & MIF to control further masculinization

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]

• a male with XX karyotype
• b/c the majority of genetic information on the Y chromosome is common to females

• 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

Müllerian Inhibiting Factor (MIF) also known as Anti-Müllerian Hormone (AMH)

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)

Testosterone

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)

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

• 17 weeks for males
• ~20 weeks for females (internal)
• preterm females tend to have a more developed clitoris than other structures (eg. labia minora)
• 

• errors in steroid synthesis
• (21-Hydroxylase, 17α-Hydroxylase, 18-Hydroxylase, 18-Oxidase, etc.)

• • Turner’s Syndrome – gonadal dysgenesis (XO)
• • Klinefelter’s Syndrome – seminiferous tubule dysgenesis (XXY)

• 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

• 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)

• • Iatrogenic (exposure to androgen, progestational agents during pregnancy)
• • Congenital virilizing adrenal hyperplasia of the fetus (21 hydroxylase deficiency)

• • Androgen resistance
• • Defective testicular development
• • Congenital virilizing hyperplasia of the fetus

• 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)

• males: 9-10 y/o
• females 7 - 8 (African American) or 8 - 9
• (Caucasian) y/o
• 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

• 1. pre-adolescence
• 2. testicular enlargement begins
• 3. penile enlargement
• 4. growth of the glans penis
• 5. completion into the appearance of adult
• genitalia
• also corresponds w/ the development of male pubic hair pattern (escutcheon) & laryngeal enlargement & increased rigidity (deeper voice)
• 

• 1. spermatogenesis in seminiferous tubules of testes
• 2. androgen biosynthesis in Leydig cells of the testes
• 

• at around 26-27 years of age
• 

• 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))

DHT → testosterone → androstenedione → DHEA

• 1. Thelarche (breast development)
• 2. Pubarche (development of female pubic
• hair pattern)
• 3. Menarche (onset of menstruation)
• 

• Variable in length
• Usually anovulatory
• Irregular in cycle

the general stages of male puberty don't have to proceed in order whereas the female stages of puberty DO

• 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
• 

• 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
• 

• 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

• precocious puberty with no underlying
• cause
• is more common in females than in males

• 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

• 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

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

• 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)

• human chorionic gonadotropin (hCG)
• human chorionic somatomammotropins (hCS1/ hCS2, or placental lactogens)
• peptide hormones + neuropeptides
• placental variants of all known hypothalamic
• releasing hormones

• 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

• 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

• 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

• ↑ 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)