If there’s one thing students can universally agree on, it’s that embryology is…confusing! It often begets the question - ‘Why am I even learning this?’ I hope you’ll find the answer is that understanding embryology provides us with a greater appreciation for the atypical presentation of anatomical structures. This post breaks down determination and differentiation of gonads, internal, and external genitalia into a 3 step formula you can apply to future practice questions.
*NOTE: typical presentation of internal and external genitalia associated chromosomal sex (XX or XY) is described, this is not all inclusive of differences of sexual development (DSD) or the many anatomical variations you may encounter clinically.
- *’Typical XY’ = penis, scrotum, vas deferens, seminal vesicles, ejaculatory duct, epididymis
- *’Typical XX’ = vulva, vagina, clitorus, uterus, fallopian tubes, ovaries
| Gonads |
Testes Ovaries |
| SRY Gene |
On Y chromosome (usually) Activates TDF (testis determining factor) |
| TDF |
Activated by SRY gene Tells gonadal tissue to differentiate into testes with sertoli and leydig cells Without TDF, ovaries with granulosa and theca cells develop |
| Sertoli Cells |
Secrete anti-Mullerian hormone (AMH) Promote spermatogenesis |
| Leydig cells | Secrete testosterone |
| Granulosa Cells | Promote oogenesis |
| Theca Cells | Secrete estrogen |
| Anti-mullerian Hormone (AMH) | Prevents Mullerian (Paramesonephric) duct development |
| Mullerian (Paramesonephric) |
Typical XX internal genitalia*
|
| Wolfian (mesonephric) |
Typical XY internal genitalia*
|
| Dihydrotestosterone (DHT) |
Created by 5-alpha reductase conversion of testosterone to DHT Needed for masculinized external genitalia development
|
| Virilized | Refering to XX external genitalia that has characreristics of testosterone exposure |
So how do these factors work together? I like to approach problems by breaking it down into 3 steps:
Step 1. Gonads: Ovaries or Testes?
Ovaries develop in the absence of functioning SRY gene.
Step 2: Internal genitalia: Mesonephric or paramesonephric ducts?
"Typical" XX internal genitalia develops from Mullerian (Paramesonephric ducts) in the absence of AMH.Step 3: External genitalia
"Typical" XX extenral genitalia develops in the absence of DHT.
Practice Questions
1. congenital adrenal hyperplasia (CAH)
Classical Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive condition in which a 21-hydroxylase deficiency causes insufficient aldosterone and cortisol, and an excess of testosterone. What will the presentation of classical CAH in an XX individua be: Gonads, internal genitalia, and external genitalia?
A. Testes. Mesonephric (Wolfian) duct. Typical external genitalia.
B. Ovaries. Paramesonephric (Mullerian) duct. Virilized external genitalia.
C. No gonads. Mesonephric (Wolfian) duct. Virilized external genitalia.
D. Ovaries. Mesonephric (Wolfian) duct. Typical external genitalia.
Answer: B
Step 1: Gonads
- Ovaries
- Individual is XX and does not have the SRY gene, no TDF to create testes
Step 2: Internal genitalia
- Paramesonephric (mullerian) duct
- No SRY gene, therefore no TDF activation to tell sertoli cells to make AMH
Step 3: External genitalia
- Testosterone is converted into DHT
- DTH is responsible for typical virilized presentation of external genitalia
- In an XX individual CAH will cause virilization of external genitalia: enlarged genital tubercule/clitorus and partial fusion of labioscrotal folds
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