Biology of Reproduction, lecture on Sexual Differentiation
USD Department of Biology
Biology of Reproduction
Summers
Endocrinology
Homeostasis/Feedback
Adult Female
Steroid Production
Ovulation
Adult Male
Gonadal Axis Regulation
Sexual Differentiation
Sexual Behavior
Puberty
Reproductive Cycling
Estrous Cycles
Menstrual Cycle
Menopause
Fertilization
Fertilization Systems
Gamete Interaction
Pregnancy
Labor and Parturition
Lactation
Sexual Response & Behavior
Pheromones
STDs
text: Human Reproductive Biology4th Edition- RE Jones & KH Lopez,: pp 87-102 Acronyms/Abbreviations    end
IX. Sexual Differentiation 	

	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. within testes Wolffian derivatives become:


					(1) Vasa Efferentia 


					(2) Rete Testis


				iii. Seminiferous Tubule connect to Wolffian ducts


					(1) Spermatogonia


					(2) Sertoli Cells


				iv. 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. Anti-Mullerian Hormone (AMH, MIS, 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
MALE INDIFFERENT FEMALE
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 AMH/MIS Mullerian Ducts Fallopian Tube
Uterus
Cervix
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
		
		
			a. DHT dependent structures contain 5a-reductase


		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. AMH 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 [weak androgens + T]   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

XIII. Sexual Behavior and Orientation