Sex Deter And Sexual Dx Flashcards
Gender vs. Sex
Gender
- subjective
- individual’s subjective perception of their sex and their sexual orientation
Sex
- objective
- more factual
- biological characteristics that distinguish female from male. Distinction may be made on the basis of chromosomes, gonads, and internal & external morphologies
Sex determination
- This is the role of the?
- What determines if you are a male or a female?
- Role of the CHROMOSOMES
2. Y chromosome and its SRY gene/testes determining factor
Sex determination
1. T or F. A person with both X and Y chromosomes always looks like a man.
- Chromosomal sex vs. gonadal sex vs. phenotypic sex vs. behavioral and metabolic sex
- F! You can have X and Y chromosomes but not look like a man because the aberrations can happen in each step.
- Sex determination in mammals is a process
- In other words, you can have X and Y but doesn’t mean that you will always look like a man bc the process takes many steps and in each step, aberrations can happen.
- Most obvious: Either you have XY or XX mix of sex chormosomes. This is called the genetic gametic for chromosomal sex. Your chromosomal sex is female bc you have XX chr. Now, the presence of the Y chromosomes will determine whether you are male bc in the Y chromosome you have the SRY (Sex determining region) in the Y which will code for the SRY protein. In this sense, after this is determined, there will now be the development of the gonads. When we were developing as fetuses, our gonads are initially bipotential (indifferent) gonads. Eventually bc of the SRY in males, there will be the development of the bipotential gonad into the testis. While in the females, bc there’s no SRY, the gonads develop in the ovary. At this pt, you are a female bc your gonads are developing into ovaries so that’s part of your gonadal sex.
Now, bc the ovary has been developing, there will be secretions by the cells of the ovary. There will be the secretions of hormones like E2 and progesterone that will also help in producing the external aspects of our sexual appearance that includes external genitalia. And eventually w/ puberty, your external sex characteristics.
So at this pt, from gonads to producing the genitalia that goes w/ the ovary (that’s your uterus, vagina, vulva), then you now have the start and the development of your phenotypic sex.
With your hormone, there’ll be behavioral and metabolic sex. So in guys, there’ll be the development of the testes and the testes will have cells that produce secretions (Leydig cells secrete testosterone and they help in further differentiating the male sexual organs into the genitalia eventually the external sex characteristics but again this testosterone has to be activated first into your 5-alpha-DHT; so 1 factor is if there is no activation, you can have high levels of testosterone but bc no activation to 5-alpha, your sex characteristics may be affected and so you also have a factor: MRF (mullerian regression factor) - the Sertoli cells will also aid in further increasing the rate of differentiation of the testis to actually produce the different components of the testis (spermatic cords, etc) this is the part of your phenotypic sex
>This part begins even in your childhood but will only be fully established during puberty meaning you reach the height of your adult appearance when puberty comes
What is your karyotype?
46, XX
Total number of chromosomes you have + sex chromosome combination
Y chromosome
- Position of the centromere?
- This chromosome is said to be very specialized to maleness. Why?
- Acrocentric
2. You have MSY (Male-specific region of the Y) which is 95% and PAR (Pseudoautosomal Region) is only 5%
Two general steps in sex differentiation?
- Gonadal sex differentiation
2. Development and maintenance of sexual dimorphism
Gonadal sex differentiation
Role of hormones
Males: If you have SRY -> indifferent/bipotential gonad, through the action of SRY, dx into a testes. The testes will now dx into special cells so it will have: Sertoli ang Leydig
Females: No SRY
Bipotential gonad dx into the ovary which has granulosa cells and theca cells.
Hormones:
Leydig will secrete testosterone which will aid in further developing the testis into its more specialized form. The cells in the ovary, on the other hand, will secrete 17B-Estradiol which helps in developing the follicles of the ovary.
Gonadal ridge importance
In the early embryo, you have production of the gonadal ridge which is empty. Then, primordial germ cells migrate there and eventually, it will be filled and dx into testes or ovary depending on the TFs that will dictate the change.
Origin of the Gonads?
The gonads originate as bilateral swellings in the intermediate mesoderm arising from the coelomic epithelium and underlying urogenital mesenchyme
Primordial Germ Cells (PGCs)
- T or F. They come immediately from the gonads.
- Migration begins when? Ends when?
- T or F. The PGCs become the sperm or the ova depending on the karyotype.
- False! The PGCs come from the yolk sac so they travel and dadaan pa sa mesentery
- Migration starts at the 5th week of embryo development and nakaabot na sila at 7th week
- F! These primordial germ cells become the sperm or the ova BUT the dx of these germ cells into the sperm or ova does NOT depend on XY or XX karyotype. SO IN OTHER WORDS, akala niyo basta XX or XY, okay na buhay niyo..NO!! Madami pang steps. Bc eventually when they reach the gonadal ridge, the cells there (neighboring somatic cells surrounding the gonads) will eventually have a greater influence on whether they will dx into ova or sperm so laking factor sila.
Gonadal sex differentiation
>What happens to the medulla and cortex when you have 46, XX? 46, XY?
> You have an inner medulla and outer cortex
So if you have 46, XY karyotype, the medullary portion of the gonad develops to become the testis and the cortex regresses
If you have a 46, XX karyotype, your cortex will be the one to develop and the medulla regresses
Development of genital ducts
When you still had undifferentiated gonads (gonads are still developing), there are 2 ducts that also develop: Mullerian and Wolffian duct.
> For males: bc of all the signals and TFs that was released, their Wolffian ducts are the ones that develop and Mullerian ducts regress.
Opposite in ladies: Mullerian ducts develop
Your Wolffian ducts develop into you epididymis, vas deferens, parts of seminal vesicles
In the females, since walang SRY and signaling so eventually their mullerian will form into the oviducts, uterus, and vagina
WOLFFIAN: Big bad wolf
Mullerian; Motherly
Phenotypic differentiation
>How many holes in the external genitalia of males? Females?
Males: 2 (Urethra and anus)
Females: 3 (Urethra, vaginal opening, anus)
SRY
- Encodes for?
- What does it do to testicular differentiation genes? ovarian differentiation genes?
- Main TFs in testis differentiation and regulation of their expression in Sertoli cells?
- SRY protein
- Activates testicular dx genes but represses ovarian dx genes throught the Wnt/Beta-catenin signaling pathway
- SRY and Sox9
You see here that there are two main TFs involved. In fact, once dx has begun, parang tapos na role ni SRY but in the processes of developing its actions, it turns off ovarian genes, it turns on testicular genes. It also promotes the transcription of the genes that will produce your Sox9 which is another TF. And your Sox9 together with SRY bind to promoters of many common targets involved in testis dx and regulate their expression (All the undx cell tinatarget para mapromote dx into maleness)
>So your Sox TF will now keep this off and turn on even more genes
>Bakit may circles? Your SRY has specific target cells/areas where it does all these things (383 identified). Your Sox9 targets 1903 areas na siya lang in charge to maintain the same thing na ginagawa ni SRY but specific to Sox9 so as seen here madaming possibilities for aberrancy.
>Between the two of them, they have a commonality ~907 targets.
The first thing that develops to aid in the bipotential gonad differentiation?
Sertoli cell
Role of Somatic cells:
Sertoli cells
1. secrete your? Effect?
Granulosa cells
1. Critical component of?
Q: What comes directly from your undifferentiated gonad?
Sertoli cells
1. Anti-Mullerian Hormone so the Mullerian duct regresses and it promotes dx of your testis into cords containing your developing spermatocytes.
Granulosa cells
1. Critical component of the ovarian follicle that helps lead to the development of the mature oocyte
The granulosa cells is the only one that directly comes from the undifferentiated gonad.
Retinoic acid in gonad differentiation?
RA induces STRA8 expression leading to germ cell meiosis and oocyte development.
Puberty
- First hormonal change?
- Involves what two physiological processes?
Pulsatile release of GnRH triggered by the disinhibition of the HPG axis
Two physiological processes
- Gonadarche
- physical and functional maturation of the gonads such that they produce gametes and sex steroids - Adrenarche
- increased production of steroids: DHEA, HEAS, A4 by the adrenal cortex
*Pubarche - growth of pubic hair
Gonadarche
- Induced by?
- Why do you suddenly grow during puberty?
- Event occurring males during gonadarche? Females?
- Induced by a marked increase in FSH and LH production by HP axis
- Adolescent growth spurt is due to gonadal steroids whether testosterone or estrogen, function of GHs, and insulin-like GFs
3.
Males: Spermarche - initiation of sperm production by the testes
Females: Folliculogenesis (development of more ovarian follicles), menarche (initiation of the menstrual cycle), and thelarche (development of breasts)
Patterns of gonadotropin levels throughout the life of a female?
Bakit inhibited GnRH
>Sa guys medyo stable, sa babae may monthly surges
>If you notice, during fetus and infancy, mataas naman yung lvls ng FSH and LH but pagka the baby is born, it goes really down; then there is a wait for puberty then eventually there will be monthly surges of FSH and LH
>One way to look at it: In children, sobrang baba ng GnRH so that mababa rin FSH and LH (even w/ such a low lvl of FSH and LH, the child’s hypothalamus is supersensitive) so kahit v low lvls of FSH and LH, the inc sensitivity of hypothalamus makes negative feedback very strong
>As there is development into adolescence, the sensitivity to LH and FSH becomes lower so less sensitive na ngayon yung hypothalamus so since less sensitive na hypothalamus, tumataas ng FSH and LH. The negative feedback is also low so it waits until mataas bago magnegative feedback so there’ll be an apparent increase to maintain homeostasis so pag child, konting ano lang, FSH and LH, negative feedback so wala ding GnRH pero pag tumatanda, manhid na manhid na hypothalamus so kailangan tumataas na FSH and LH para may response. So even high lvls now ill not inhibit GnRH and sabi nga sa females, it’s not 1 big surge, onti onti yan kaya sa start ng puberty sa females, di agad naman full menses na maraming menstrual cycles ang female na unovulatory.
Tanner stages
- What is it?
- Onset of puberty
- Basis
- In females, how can you say that she is starting puberty?
- In males, what is the first sign of puberty?
- Five development stages that document the process of puberty
- Females - 8-13 y.o., Males - 9-14 y.o.
* Differs per race - Based on the extent of pubic hair growth, genital, and breast development
- There should be a breast bud below the areola
- Increase in the volume (size) of the testicles
First sign of full-termness of baby?
Sign of newborn with ambiguous genitalia?
Male:
>Bilateral (2) testicles that are descended
>Complete formation of scrotal folds with midline fusion, pigmentation
>Penile length of 3.5 +/ 0.4 cm
Female
>Bilateral separation labial folds
>No palpable mass (gonads)
>Separate urethral and vaginal openings
NB w/ Ambiguous genitalia >Bilateral cryptochidism >Bifid scrotum (so it looks like a big labia) >Hypospadia >Labial fusion >Palpable gonads
- Nowadays, the term is not an acceptable term. What replaced it?
- Define #1
- Disorders of sex development (DSD)
- Heterogenous group of congenital discrepancy between external genitalia, gonadal and chromosomal sex (atypical devt of internal and external genitalia)
Pseudohemaphrodites are now termed as?
Either 46, XY DSD or 46, XX DSD
