. Biology of Reproduction, lecture on Sexual Differentiation, text only

Biology of Reproduction

Fall 1998

text: Human Reproductive Biology 2nd Edition - R.E. Jones: Read pages 117-135 for this lecture


IX. Sexual Differentiation 			back to VIII. Adult Male

	A. Chromosomes

		1. Autosomes

			a. 22 homologous pair

			b. control general somatic function

		2. Sex chromosomes

			a. 1 pair, may be dissimilar,
			    but not all vertebrates have sex chromosomes

				i. turtles, crocodilians + some lizards have
				    temperature dependent sex determination

			b. X and Y in mammals
mammals birds, amphibians, some fish
i. XX ZW = female symbol = female
ii. XY ZZ = symbol for male = male

	B. Gonads

		1. Indifferent Stage = Weeks 5-7 of development (in humans)

			a. Mesonephric Kidney

				i. Mesonephric duct = Wolffian Duct

				ii. Paramesonephric duct = Mullerian Duct

			b. Genital Ridge

				i. epithelium

				ii. stroma

			c. 4th week (human)

				i. Primordial Germ Cells arrive from Yolk Sac

					(1) into the genital ridge

					(2) ~100 start in yolk sac

					(3) ~850 arrive at genital ridge

						(a) mitosis

				ii. Rete Chords grow into gonad

		2. Male

			a. Week 7-10 differentiation into Testes

				i. Rete Cords
				ii. Medullary Cords

			b. Week 16-17 (human)

				i. Wolffian Duct becomes:

					(1) Ductus Epididymis

					(2) Vas Deferens

						(a) Ejaculatory Duct

					(3) Seminal Vesicle

				ii. Vasa Efferentia 

				iii. Rete Testis

     			iv. Seminiferous Tubule

					(1) Spermatogonia

					(2) Sertoli Cells

				v. Mullerian Duct degenerates

					(1) a small piece remains in the prostate

						(a) Prostatic Utricle

		3. Female

			a. Cortical Cords

			b. Oogonia

			c. Primary Oocyte

			d. Mullerian Duct  becomes:

				i. Fallopian Tubes

				ii. Uterus

				iii. Cervix

				iv. upper 1/3 Vagina

			e. Paired Mullerian development

				i. fusion

					(1) different degree of fusion is represented
					    in different vertebrate forms

	C.  Regulation of gonadal sex

		1.  when sex chromosomes are present,
		    heterozygous sex chromosomes determine sex

			a. via production of regulatory sex determining factors

				i. i.e. without biochemical intervention the sex
				   associated with homozygous sex chromosomes occurs

		2. TDF   testis determining factor

			a. coded for by a gene: SRY

				i.  Sex determining Region
				    of the 1A1 on the short arm of the
					 Y chromosome

			b.  indifferent gonad becomes testis in the presence of  TDF   

		3. Mullerian Duct Inhibiting Factor (MDIF, MDI, MDIH, MDIS)

			a. glycoprotein secreted by Sertoli cells

			b. inhibits development of
			   Mullerian duct-derived structures

			c. Anti-cancer agent for cancers
			   of the Mullerian duct and Ovarian cancer

				i. ovarian surface epithelium is homologous
				   to Mullerian epithelium

				ii. includes prostate cancer - prostatic utricle

	D. External Genitalia

		1. Indifferent 5-7 weeks

			a. Genital Tubercle (phallus)

			b. Labio-Scrotal Swelling

			c. Urogenital Fold

			d. Urethral Groove

		2. differentiated gonads are necessary for differentiation of external genetalia
3. Female 8-10 weeks 4. Male 7-10 weeks
a. Clitoris from genital tubercle = a. Glans Penis
b. Labia Majora = b. Scrotum
i. scrotal raphe
c. Labia Minora = c. Corpus Spongiosum
i. penile raphe
d. Vestibule = urogenital sinus
e. Vaginal Introitus

	E. Hormones & Factors Necessary for Development
Testis TDF Gonad none Ovary
Vasa Efferentia T Mesonephric Tubules No functional structure
Rete Ovari
Ductus Epididymis
Vas Deferens
Ejaculatory Duct
Seminal Vesicles
T Wolffian Ducts
(Mesonephric Ducts)
No functional structure
No functional structure MDIF Mullerian Ducts Fallopian Tube
Upper 1/3 Vagina
Glans Penis
Corpora Cavernosa
of the Penis
DHT Genital Tubercle Glans
Corpora Cavernosa
of the Clitoris
Corpus Spongiosum
of the Penis
DHT Urogenital Folds Labia Minora
Scrotum DHT Labio-Scrotal Swelling Labia Majora
Prostate Gland

Bulbourethral Gland
DHT Urethral Tissue Lesser Vestibular
(Skenes) Gland
Greater Vestibular
(Bartholins) Gland

		1. Structures dependent on DHT convert T intracellularly

		2. Development of Female structures does not require hormone intervention

	F. Intersex

		1. ambiguous reproductive tract

		2. True Hermaphrodite

			a. combination gonadal type

				i. ovotestes

				ii. 1 ovary and one testis = gynandromorph

		3. Pseudohermaphrodite

			a. gonads normal for that sex

				i. xx=ovary,  xy=testis

			b. ducts or external genitalia may be of the opposite sex

			c. Testicular Feminization Syndrome

				i. genetic defect - no androgen receptors 

					(1) for T or DHT

				ii. normal testis formed, no testicular descent

					(1) i.e. cryptorchid testes

				iii. MDIF causes degeneration of Mullerian Duct

				iv. no Wolffian Duct Development

				v. female external genetalia

			d. Guevedoces

				i. genetic inability to make 5a-reductase

				ii. normal testis formed, no testicular descent

				iii. normal T levels, Leydig cells remain normal

				iv. normal Wolffian Duct development

				v. female external genetalia
				   and prostate (lesser vestibular)

				vi. at puberty high [T + weak androgens]   bind A-R

					(1)  voice lowers

					(2)  clitoris becomes penis,
					     scrotum fuses,
						 descent of testes

					(3)  prostate and masculine hair remain undeveloped

			e. Adrenogenital Syndrome (Congenital Adrenal Hyperplasia)

				i. genetic inability to convert  to cortisol in XX

				ii. very high ACTH levels

				iii. high androgens from adrenal

				iv. ducts remain the same, happens after duct differentiation

				v. masculinization

					(1) hirsutism

					(2) clitoral growth

					(3) growth of labia majora

X. Sexual Behavior and Orientation