Reproductive

Carcinoma from squamous epithelial lining of vulva.  - Presents with leukoplakia, biopsy often required to distinguish carcinoma from other causes. HPV-related vulvar carcinoma - Associated with high-risk HPV types 16, 18. - Risk factors: multiple partners, early coitarche. Usually in reproductive-age females. Non-HPV vulvar carcinoma - Usually from long-standing lichen sclerosus.- Females >70 years old.

Intraepithelial adenocarcinoma. Carcinoma in situ, low risk of underlying carcinoma. Presents with pruritus, erythema, crusting, ulcers.

Follicular cyst: Distention of unruptured graafian follicle. - May be associated with hyperestrogenism, endometrial hyperplasia. - Most common ovarian mass in young women. Theca-lutein cyst: Often bilateral/multiple.- Due to gonadotropin stimulation.- Associated with choriocarcinoma and hydatidiform moles.

Malignant, hemorrhagic testicular germ cell tumor with necrosis. - Painful - Often glandular/papillary morphology "Pure" embryonal carcinoma is rare; most commonly mixed with other tumor types. - May be associated with ↑ hCG and normal AFP levels when pure (↑ AFP when mixed). - Worse prognosis than seminoma.

- Characterized by dysuria, frequency, urgency, low back pain. - Warm, tender, enlarged prostate. Acute bacterial prostatitis – in older men most common bacterium is E coli; in young males consider C trachomatis, N gonorrhoeae. Chronic prostatitis – either bacterial or nonbacterial (eg, 2˚ to previous infection, nerve problems, chemical irritation).

Vitamin D:- Exclusive breastfeeding- Lack of sunlight exposure- Dark skin pigmentation Iron:- Preterm/low-birthweight

Within week 1: hCG secretion begins around the time of implantation of blastocyst (day 6). Within week 2: Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers. Within week 3: Gastrulation forms trilaminar embryonic disc. Cells from epiblast invaginate → primitive streak → endoderm, mesoderm, ectoderm. Notochord arises from midline mesoderm; overlying ectoderm becomes neural plate. 3 weeks = 3 layers. Weeks 3-8 (embryonic period): Neural tube formed by neurectoderm and closes by week 4. Organogenesis. Extremely susceptible to teratogens.- Week 4: Heart begins to beat. Upper and lower limb buds begin to form. 4 weeks = 4 limbs and 4 heart chambers.- Week 6: Fetal cardiac activity visible by transvaginal ultrasound.- Week 8: Fetal movements start. Week 10: Genitalia have male/female characteristics.

Agenesis = Absent organ due to absent primordial tissue.Aplasia = Absent organ despite presence of primordial tissue.Hypoplasia = Incomplete organ development; primordial tissue present.Disruption = 2° breakdown of previously normal tissue or structure (eg, amniotic band syndrome).Deformation = Extrinsic disruption; occurs after embryonic period.Malformation = Intrinsic disruption; occurs during embryonic period (weeks 3-8).Sequence = Abnormalities result from a single 1° embryologic event (eg, oligohydramnios → Potter sequence).

Composed of branchial clefts, arches, pouches. Branchial clefts – derived from ectoderm. Also called branchial grooves. Branchial arches – derived from mesoderm (muscle, arteries) and neural crest (bones, cartilage). Branchial pouches – derived from endoderm.

1st branchial arch:- Cartilage: Maxillary process → Maxilla, zygomatic bone; Mandibular process → Meckel cartilage, Mandible, Malleus and incus, sphenomandibular ligament- Muscles: Muscles of Mastication (temporalis, masseter, lateral and medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, anterior 2/3 of tongue, tensor veli palatini- Nerves: CN V3 2nd branchial arch: - Cartilage: Reichert cartilage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament- Muscles: Muscules of facial expression, Stapedius, Stylohyoid, platysma, posterior belly of digastric- Nerve: CN VII  3rd branchial arch:- Cartilage: Greater horn of hyoid- Muscles: Stylopharyngeus - Nerve: CN IX 4th-6th branchial arches:- Cartilage: Arytenoids, cricoid, corniculate, cuneiform, thyroid- 4th arch: Most pharyngeal constrictors, cricothyroid, levator veli palatini; CN X (superior laryngeal branch)- 6th arch: All intrinsic muscles of larynx except cricothyroid; CN X (recurrent/inferior laryngeal branch)- Arches 3 and 4 form posterior 1/3 of tongue; arch 5 makes no major developmental contributions.

1st branchial pouch:- Middle ear cavity, eustachian tube, mastoid air cells- 1st pouch contributes to endoderm-lined structures of ear 2nd branchial pouch:- Epithelial lining of palatine tonsil 3rd branchial pouch: - Dorsal wings → inferior parathyroids- Ventral wings → thymus 4th branchial pouch: - Dorsal wings → superior parathyroids- Ventral wings → ultimobranchial body → parafollicular (C) cells of thyroid DiGeorge syndrome – Chromosome 22q11 deletion. Aberrant development of 3rd and 4th pouches → T-cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development). Associated with cardiac defects (conotruncal anomalies).

Cleft lip – failure of fusion of the maxillary and merged medial nasal processes (1° palate). Cleft palate – failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelves with the nasal septum and/or medial palatine shelf (2° palate). Cleft lip and cleft palate have distinct, multifactorial etiologies, but often occur together.

1. No Sertoli cells or lack of Müllerian inhibitory factor → development of both male and female internal genitalia and male external genitalia. 2. 5α-reductase deficiency – inability to convert testosterone into DHT → male internal genitalia, ambiguous external genitalia until puberty (when ↑ testosterone levels cause masculinization)

Vagina – Stratified squamous epithelium, nonkeratinized Ectocervix – Stratified squamous epithelium, nonkeratinized Transformation zone – Squamocolumnar junction (most common area for cervical cancer) Endocervix – Simple columnar epithelium Uterus – Simple columnar epithelium with long tubular glands in proliferative phase; coiled glands in secretory phase Fallopian tube – Simple columnar epithelium, ciliated Ovary, outer surface – Simple cuboidal epithelium (germinal epithelium covering surface of ovary)

Pathway of sperm during ejaculation: Seminiferous tubules → Epididymis → Vas deferense → Ejaculatory ducts → Urethra → Penis

Erection – Parasympathetic nervous system (pelvic splanchnic nerves, S2-S4):- NO → ↑ cGMP → smooth muscle relaxation → vasodilation → proerectile.- Norepinephrine → ↑ [Ca2+]in → smooth muscle contraction → vasoconstriction → antierectile. Emission – Sympathetic nervous system (hypogastric nerve, T11-L2). Ejaculation – Visceral and somatic nerves (pudendal nerve).

Spermatogonia: - Maintain germ cell pool and produce 1° spermatocytes- Line seminiferous tubules- Germ cells Sertoli cells: - Secrete inhibin B → inhibit FSH- Secrete androgen-binding protein → maintain local levels of testosterone- Produce MIF- Tight junctions between adjacent Sertoli cells form blood-testis barrier → isolate gametes from autoimmune attack- Support and nourish developing spermatozoa- Non-germ cells- Convert testosterone and androstenedione to estrogens via aromatase- Homolog of female granulosa cells Leydig cells: - Secrete testosterone in the presence of LH; testosterone production unaffected by temperature- Interstitium- Endocrine cells- Homolog of female theca interna cells

↑ estrogen, ↑ GnRH receptors on anterior pituitary. Estrogen surge then stimulates LH release → ovulation (rupture of follicle). ↑ temperature (progesterone induced). Mittelschmerz – transient mid-cycle ovulatory pain; classically associated with peritoneal irritation (eg, follicular swelling/rupture, fallopian tube contraction). Can mimic appendicitis.

Follicular phase can vary in length. Luteal phase is 14 days.Ovulation day + 14 days = menstruation. Follicular growth is fastest during 2nd week of the follicular phase. Estrogen stimulates endometrial proliferation.Progesterone maintains endometrium to support implantation. ↓ progesterone → ↓ fertility

Fertilization most commonly occurs in upper end of fallopian tube (the ampulla). Occurs within 1 day of ovulation. Implantation within the wall of the uterus occurs 6 days of fertilization. Syncytiotrophoblasts secrete hCG, which is detectable in blood 1 week after conception and on home test in urine 2 weeks after conception. Placental hormone secretion generally increases over the course of pregnancy, but hCG peaks at 8-10 weeks. Gestational age – calculated from date of last menstrual period.Embryonic age – calculated from date of conception (gestational age minus 2 weeks) Physiologic adaptations in pregnancy:- ↑ cardiac output (↑ preload, ↓ afterload), ↑ HR → ↑ placental and uterus perfusion)- Anemia (↑↑ plasma, ↑ RBCs)- Hypercoagulability (to ↓ blood loss at delivery)- Hyperventilation (to eliminate fetal CO2)

Defined as <2500 g.  Caused by prematurity or intrautertine growth restriction (IUGR). Associated with ↑ risk of sudden infant death syndrome (SIDS) and with ↑ overall mortality.Other problems include impaired thermoregulation and immune function, hypoglycemia, polycythemia, and impaired neurocognitive/emotional development. Complications include infections, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and persistent fetal circulation.

After parturition and delivery of placenta, rapid ↓ in progesterone disinhibits and initiates lactation. Suckling is required to maintain milk production and ejection, since ↑ nerve stimulation → ↑ oxytocin and prolactin. Prolactin – induces and maintains lactation and ↓ reproductive function.Oxytocin – assists in milk letdown; also promote uterine contractions. Breast milk is the ideal nutrition for infants <6 months old. Contains maternal immunoglobulins (conferring passive immunity; mostly IgA), macrophages, lymphocytes. Breast milk reduces infant infections and is associated with ↓ risk for child to develop asthma, allergies, diabetes mellitus, and obesity. Guidelines recommend exclusively breastfed infants get vitamin D and possibly iron supplementation. Breastfeeding ↓ maternal risk of breast and ovarian cancer and facilitates mother-child bonding.

Spermatogenesis begins at puberty with spermatogonia. Full development takes 2 months. Occurs in seminiferous tubules. Produces spermatids that undergo spermiogenesis (loss of cytoplasmic contents, gain of acrosomal cap) to form mature spermatozoon.

Tanner stage is assigned independently to genitalia, public hair, and breast. Stage I: Pre-pubertal- No sexual hair ♂♀- Flat appearing chest with raised nipple ♀ Stage II: ~8-11.5 years- Pubic hair appears (pubarche) ♂♀- Testicular enlargement ♂- Breast bud forms (thelarche) ♀ Stage III: ~11.5-13 years- Coarsening of pubic hair ♂♀- Penis size/length ↑ ♂- Breast enlarges, mound forms ♀ Stage IV: ~13-15 years- Coarse hair across pubis, sparing thigh ♂♀- Penis width/glans ↑ ♂- Breast enlarges, raised areola, mound on mound ♀ Stage V: Usually >15 years- Coarse hair across pubis and medial thigh ♂♀- Penis and testis enlarge to adult size ♂- Adult breast contour, areola flattens ♀

47, XYY. - Phenotypically normal (usually undiagnosed)- Very tall- Normal fertility- May be associated with severe acne, learning diability, autism spectrum disorders.

46,XX > 46, XY - Both ovarian and testicular tissue present (ovotestis)- Ambiguous genitalia - Previously called tur hermaphroditism.

Disagreement between the phenotypic sex (external genitalia, influenced by hormonal levels) and the gonadal sex (testes vs ovaries, corresponds with Y chromosome). Includes the terms pseudohermaphrodite, hermaphrodite, and intersex. 46,XX DSD – Ovaries present, but external genitalia are virilized or ambiguous. Due to excessive and inappropriate exposure to androgenic steroids during early gestation (eg, congenital adrenal hyperplasia or exogenous administration of androgens during pregnancy). 46,XY DSD – Testes present but external genitalia are female or ambiguous. Most common form is androgen insensitivity syndrome (testicular feminization).

⊕ Uterus, ⊝ Breasts:- Hypergonadotrophic hypogonadism (eg, Turner syndrome, genetic mosaicism, pure gonadal dysgenesis)- Hypogonadotropic hypogonadism (eg, CNS lesions, Kallmann syndrome) ⊝ Uterus, ⊕ Breasts:- Uterovaginal agenesis in genotypic female or androgen insensitivity in genotypic male ⊝ Uterus, ⊝ Breasts: Male genotype with insufficient production of testosterone

Nipple Lacitferous duct → Major duct- Intraductal papilloma- Abscess/mastitis- Paget disease Terminal duct lobular unit- Fibrocystic change- DCIS, ductal carcioma- LCIS, lobular carcinoma Stroma- Fibroadenoma- Phyllodes tumor

~95% of all testicular tumors.- Most often occur in young men- Risk factors: Cryptorchidism, Klinefelter syndrome- Can present as mixed germ cell tumor - Does not transilluminate - Usually not biopsied (risk of seeding scrotum), removed via radical orchiectomy. Types:- Seminoma- Yolk sac tumor- Choriocarcinoma- Teratoma- Embryonal carcinoma

Transection of the vas deferens.- The vas deferens functions not only as a transport duct from the epididymis to the ejaculatory duct but also serves to store and protect sperm following spermatogenesis. - Vasectomy blocks the transport of new sperm from the epididymis but has no effect on sperm distal to the ligation.- Patients can still have viable sperm in the distal vas for 3 months and at least 20 ejaculations following vasectomy.

Autosomal recessive disorder that manifests early in embryonal life with high androgen and low estrogen levels in the female fetus. Maternal virilization (eg, hirsuitism) commonly occurs during pregnancy due to the transfer of excess androgens into the maternal circulation. Affected newborn girls have normal internal genitalia and ambiguous or male-type external genitalia (eg, clitoromegaly, female pseudohermaphrodism)

- Prematurity, low birth weight - Sudden infant death syndrome - Middle ear disease (eg, otitis media) - Asthma - Respiratory tract infections (eg, bronchitis, pneumonia)

1st cleft develops into external auditory meatus. 2nd through 4th clefts form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme. Persistent cervical sinus → branchial cleft cyst within lateral neck, anterior to sternocleidomastoid muscle.

Disorder caused by defective formation of the 1st and 2nd branchial arches. Clinical features:- Micrognathia- Glossoptosis → airway obstruction- Cleft palate

Disorder caused by defective neural crest cell migration into the first and second branchial arches.- Autosomal dominant Clinical features:- Cleft palate- Slanting eyes (with the lateral canthi more inferior than the medial canthi)- Maxillary and mandibular hypoplasia (depressed cheekbones and overbite)- Ear deformities with conductive hearing loss