embryo

• KEY REGULATORY GENES

  1. Key to sexual dimorphism - Y chromosome
  2. Master gene for testis formation - SRY
  3. Master gene for ovary formation - WNT-4
  4. Known to bind to promoter region of a transcription factor which promotes & elevates AMH synthesis - SOX-9
  5. Induces penetration of mesonephric tubules to hilum of indifferent gonad - FGF-9
  6. Stimulate differentiation/formation of Sertoli & Leydig cells - SF-1
  7. Inhibits SOX-9 function which permits Müllerian ducts differentiation into female internal genitalia - DAX-1
  8. Known ovarian “follicular cells” key regulator - TAFii105
• GENES AND CHROMOSOMAL LOCI

  1. SRY - Yp11
  2. FGF-9 - Ch13q11-12
  3. SF-1 - Ch9q33.3
  4. DAX-1 - Xp21.3-21.2 (30,082,120 - 30,087,136th DNA base pairs)
  5. WNT-4 - Ch1
  6. SOX-9 - Ch17q24-25
  7. TAFii105 - Chromosome 18q11.2
• PRIMORDIAL GERM CELLS (MONITORED LOCATION IN WEEKS AOG)

  • 3rd - In the most caudal part of the yolk sac near the allantois
  • 4th - PGCells migrate via amoeboid movement from allantois, cloaca, hindgut, dorsal mesentery of hindgut (yACHt)
  • 5th - Hilum of the indifferent gonad
  • 6th - Penetrates the mesenchyme/parenchyma of the indifferent gonad
  • 7th - Gonad start to differentiate into either “ovary” or “testis” through PGCells’ secreted hormone
• DERIVATIVES OF INDIFFERENT GONAD (CELLULAR DEVELOPMENT)

  SURFACE CORTICAL EPITHELIUM

  1. Follicular cells surrounding the egg cells/female PGCells
  2. Sertoli cells within the forming Seminiferous tubules

  MEDULLARY MESENCHYME

  1. Theca interna cells of primordial ovary
  2. Leydig cells of primordial testis
• INDIFFERENT STAGE 


  • 7TH WEEK AOG - The earliest week you could use GONAD in determining the sex of the embryo/fetus
  • 8TH WEEK AOG - The earliest week you could use the DUCTAL SYSTEM/INTERNAL GENITALIA in the determining the sex of the embryo/fetus
  • 12TH WEEK AOG - The earliest week you could use the EXTERNAL GENITALIA in identifying the sex of the fetus
• INDIFFERENT STAGE 


  A specific sub-period/stage during embryonic period where in you CANNOT tell yet if:

  1. Gonad will become testis or ovary;
  2. Wollfian duct will stay or Mullerian duct will stay to become the embryo’s internal genitalia;
  3. Cloacal folds will become penis-scrotum or clitoris-labia as embryo’s external genitalia.
• PERIOD COVERED BY INDIFFERENT STAGE

  3rd until 6th week AOG: Indifferent Stage for Gonad

  3rd until 7th week AOG: Indifferent Stage for Internal Genitalia

  3rd until 11th week AOG: Indifferent Stage for External Genitalia
• MAIN ANLAGE AND ADULT STRUCTURES

  1. Indifferent Gonad
  2. testis or ovary
  3. Wolffian Ducts (Mesonephric Duct)
  4. male internal genitalia
  5. Mullerian Ducts (Paramesonephric duct)
  6. female internal genitalia
  7. Cloacal Folds
  8. male external genitalia
  9. female external genitalia
• DURING 8TH WEEK AOG (FEMALE)


  WOLFFIAN DUCT will:

  degenerate except for the most proximal end and the most caudal end

  • most proximal -> Epoophoron (Gland of Rosenmuller) and Paroophoron (Gland of Johnson)
  • most distal -> Longitudinali Epoophori (Gartner’s Duct)

  MULLERIAN DUCT will become:

  • Fallopian tubes
  • Uterus
  • Cervix of the uterus
  • Upper 3 rd of the vagina
• EMBRYONIC STRUCTURES AND ADULT DERIVATIVES


  Mesonephric duct (Wolffian duct)

  • Epididymis & Paradidymis
  • Vas deferens
  • Ejaculatory duct
  • Ductuli efferentes
  • Paroophoron of Johnson’s
  • Epoophoron of Rosenmüller
  • Gartner’s duct

  Paramesonephric duct (Mullerian duct)

  • Appendix testis of female
  • Utriculus Prostaticus of female
  • Fallopian tube
  • Uterus & Cervix of the Uterus
  • Upper 3rd of the vagina canal

  Testicular cords

  • Seminiferous Tubule
  • Rete testis

  Sinovaginal bulbs (female posterior urogenital sinus)

  • lower 2/3rd of the vagina (external Genitalia)
• FATE OF MULLERIAN DUCTS

  • Upper Vertical 3rd of Müllerian Ducts - Distal 1⁄2 of Fallopian Tube
  • Middle Horizontal 3rd of Müllerian Ducts - Proximal 1⁄2 of Fallopian Tube
  • Fused Lower Vertical 3rd’s of Müllerian Ducts called “Unaleria” - Uterus
  • Caudal-most tip of Unaleria called “Paramesonephric tubercle” - Cervix of the Uterus; Portio-vaginalis of Uterus; 4 fornices & Upper 3rd of the Vagina
• ANLAGE OF VAGINA -> DIFFERENTIATION

  • Sinovaginal Bulbs -> Lower 2/3rd of Vagina
  • “Paramesonephric Tubercle” of the unaleri—> Upper 3rd of Vagina
• EMBRYONIC ORIGIN (parts of cloacal folds) and MALE ADULT DERIVATIVES

  • Genital tubercle - Corpora cavernosa + dorsal half of penile shaft & dorsal half of prepuce + Glans penis
  • Urethral folds - Spongy urethra + Corpus spongiosus + ventral half of penile shaft & ventral half of prepuce
  • Anal folds - External Anal Sphincter
  • Genital Swelling - scrotum
  • Cloacal Membrane - Wall of penile spongy urethra
  • External Urethral Meatal Plug (ectoderm) - Navicular fossa of Glans penis (last 2cm of penile urethra)
• EMBRYONIC ORIGIN (parts of cloacal folds) and FEMALE ADULT DERIVATIVES

  • Genital tubercle - Clitoris + Clitoral Hood
  • Urethral folds - Labia Minora + Fourchette
  • Anal folds - External Anal Sphincter
  • Genital Swelling - Labia Majora
  • Cloacal Membrane - Hymen + Vestibule
• GERM LAYER OF ORIGIN AND REPRODUCTIVE STRUCTURES

  • ECTODERM

  1. External Genitalia (except prostate gland; lower 2/3rd’s of vagina; wall of male urethra; internal lining of hymen) from CLOACAL FOLDS

  • ENDODERM

  1. Prostate gland; lower 2/3rd’s of vagina; wall of male spongy urethra; & internal lining of hymen

  • MESODERM

  1. Gonads
  2. Wolffian Duct & Mullerian Duct

  • UNDIFFERENTIATED AND NON-LYONIZED EPIBLAST

  1. Primordial Germ Cells (e.g. first colony of sperm/egg cells)
• EMBRYONIC ORIGIN AND TESTICULAR ENSHEATHING DURING DESCENT (ICE-TIE)

  • External Oblique Aponeurosis - External Spermatic Sheath is from
  • Internal Oblique Aponeurosis - Cremasteric Fascia & Cremasteric Muscle are from
  • Transversus Abdominis Aponeurosis - NO PARTICIPATION as it arches over the descending testes
  • Transversalis Fascia - Internal Spermatic Sheath is from
• DEVELOPMENTAL MILESTONES DURING DESCENT OF TESTIS (IN WEEKS AOG)

  • 8TH WEEK - Testes are located in the posterior abdominal wall retroperitoneally
  • 12TH WEEK - Testes have reached the pelvic brim/inguinal ring region near symphysis pubis
  • 28TH WEEK - Testes begin to descent through the inguinal canal
  • 33RD WEEK - The earliest time testes have contacted the scrotal floor
• DURING 8TH WEEK AOG (MALE)


  WOLFFIAN DUCT will become:

  • Ductuli efferentes
  • Epididymis
  • Paradidymis
  • Vas/ductus deferens
  • Seminal vesicle
  • Ejaculatory duct

  MULLERIAN DUCT will:

  degenerate except for the MOST PROXIMAL END and the MOST CAUDAL END.

  • most proximal -> Appendix Testis (non-functional fallopian tube of males)
  • most caudal -> Utriculus Prostaticus (non-functional uterus of males)
• FEMALE GENITAL TUBERCLE

  will differentiate into: clitoris and clitoral hood
• FEMALE URETHRAL FOLDS


  will differentiate into: labia minora
• FEMALE GENITAL SWELLINGS


  will differentiate into: labia majora
• MALE GENITAL TUBERCLE


  will differentiate into: Dorsal glans (head of) Penis and Corpora Cavernosa
• MALE URETHRAL FOLDS 


  will differentiate into: Ventral spongy urethra and Corpus Spongiosum
• MALE GENITAL SWELLINGS


  will differentiate into: scrotum
• CLOACAL FOLDS 


  will differentiate into: external genitalia
• 33rd WEEK AOG


  Earliest time the testis hits the scrotal floor during descent
• 12TH WEEK AOG


  Earliest time “EXTERNAL GENITALIA (Cloacal Folds)” can be used as a lone basis to identify the PHENOTYPIC SEX of the Embryo-Fetus
• 8TH WEEK AOG


  Earliest time “DUCTAL SYSTEM (Internal Genitalia)” can be used as a lone basis to identify the PHENOTYPIC SEX of the Embryo-Fetus
• 7TH WEEK AOG


  Earliest time “GONAD” can be used as a lone basis to identify the PHENOTYPIC SEX of the Embryo-Fetus
• REMNANTS OF MULLERIAN DUCTS INSIDE MALE’S BODY

  • Appendix testis
  • Utriculus prostaticus
• REMNANTS OF WOLFFIAN DUCTS INSIDE FEMALE’S BODY

  • Epoophoron (Gland of Rosenmuller)
  • Paroophoron (Gland of Johnson)
  • Longitudinali Epoophori (Gartner’s Duct)
• HILUM OF TESTIS


  Estimated location of “primordial germ cells” (maturing gametes/sperm & egg cells) during 5th Week AOG
• INSIDE TESTIS


  Estimated location of “primordial germ cells” (maturing gametes/sperm & egg cells) during 6th Week AOG
• YOLK SAC 


  Estimated location of “primordial germ cells” (maturing gametes/sperm & egg cells) during 3rd Week AOG
• SOX-9


  reason why males do NOT have fallopian tubes, uterus, cervix, and upper 3rd of the vagina
• WNT-4


  Master gene for “ovary” formation
• SRY


  Master gene for “testis” formation
• PARAMESONEPHRIC TUBERCLE will differentiate into: Upper 3rd of the vaginal canal and cervix of the uterus
• UNALERIA

  will differentiate into: uterus
• SINOVAGINAL BULBS


  will differentiate into: Hymen and lower 2/3rd’s of the vaginal canal