AnSci 434 - updated 2/2/98

Handout 3: The Development of Sexuality

Sexual differences are expressed at several levels of development that include: 1) chromosomal or genetic sex, 2) gonadal sex, 3) hormonal sex, 4) phenotypic or somatic sex and 5) brain, psychic or behavioral sex.

Development of female gonads, reproductive tract, genitalia, phenotype and behavior is the default pathway and is referred to as feminization. The formation of a male pattern or masculinization is triggered by series of specific events initially activated by genes on the Y chromosome.

A. Genetic Sex:

In mammals the heterogametic sex is the male with the presence of an X and Y chromosome. It is the SRY gene located on the Y chromosome which is responsible for initiating the sequence of events that leads to masculinization of the developing fetus. In mammalian females, two X chromosomes are present and in the absence of the Y chromosomes, these fetuses feminize and develop into females.

 

A much more complex situation occurs in birds. It is the females which are the heterogametic sex ( ZW) yet these developing embryos are feminized. Surprisingly it is the male which is the default pathway and the homogametic sex (ZZ). Further, the Z chromosome codes for SRY. It is hypothesized that the W chromosome contains a gene which counteracts the effects of SRY in females and allows feminization.

B. Gonadal Sex:

1. The undifferentiated gonad develops from the mesonephric kidney (primitive kidney found in developing fetus).
   
   
2. The diploid germ cells, XX and XY, both originate near the hind gut of the embryo. They originate from coelomic epithelium that is derived from endoderm, then migrate to the yolk sac and infiltrate the undifferentiated gonad. They do not direct the development of the gonad or sexuality.
   
   
3. Cells of the undifferentiated gonad that arise from the mesonephric kidney posses either XX or XY sex chromosomes. If XY and male, the cells produce a cell organizing-protein that was originally termed the testis determining factor (TDF). It has since been identified that TDF is the product of the SRY gene on the Y chromosome and so this protein is now referred to as the SRY protein.
   
   
4. The SRY protein
   
   
   1. It is a DNA binding protein that either enhances other transcription factors or is itself a transcription factor. The result of SRY expression is that a series of genes are transcribed and the resulting proteins either directly or indirectly causes the development of primary sex cords which will later be called seminiferous tubules. These sex chord form within the medulla (central part) of the undifferentiated gonad. Thus the gonad becomes a testis. The testis will then secret both testosterone and Mullerian duct inhibiting substance (MIS). In older texts, you may run across a discussion of how the Hy antigen controls testicular development. This factor was produced by the Hy gene on the Y chromosome and was once thought to be the TDF. This was eventually proven to be false and is no longer present in current texts.
      
      
   2. In the absence SRY protein, the medullary cords regress and secondary sex cords form in the cortex (surface area) of the gonad. These will become the egg nests that will contain the follicles. The gonad will be known as an ovary.
      
      
5. Primordial germ cells are incorporated into:
   
   
   1. The sex cords regardless of whether they are XX or XY.
      
      
   2. Because all male cells normally contain XY chromatin, the seminiferous tubules developed in response to the SRY protein and incorporate XY germ cells. Likewise in females, the follicles of the ovary generally enclose XX germ cells.
      
      
   3. Germ cells within seminiferous tubules (usually XY) are allowed by the tubule to divide and multiply by mitosis from this point throughout the animal's life, or until in the adult, some undergo meiosis to become haploid spermatozoa.
      
      
   4. Germ cells in ovaries multiply by mitosis until surrounded by follicle cells. At the beginning of follicle enclosure the primordial germ cells differentiate into oogonia and then start meiosis but are surrounded by follicle cells before meiosis can be completed. The follicle cells arrest or are prevent the germ cells from completing meiosis until puberty. At or after puberty, selection of follicles for growth and ovulation occurs. At this time, meiosis resumes and is completed only after activation of an egg by the fertilizing sperm.
      
      
6. From the sequence of events triggered by the SRY protein, the Leydig cells will differentiate in the spaces between seminiferous tubules.
   
   
7. Leydig cells produce testosterone, starting around day 35 of gestation in most farm animals.
   
   
8. The freemartin condition in cattle (female masculinized by being co-twin with a male) appears to result from early placental transfer of cells from the male into the female. These cells then go on to form SRY protein in the female. In response the female is masculinized to various extents and usually becomes what is known as a psuedohermaphrodite (contains nonfunctional portions of both male and female reproductive tracts).

C. Hormonal Sex:

1. Fetus is basically feminine.
   
   
2. Male is a female masculinized by testicular components: 1) testosterone and 2) a Mullerian duct inhibitory substance (MIS) which may also be called Anti-Mullerian Hormone (AMH).
   
   
3. Female reproductive tract and glands develop from fetal Mullerian ducts, portions of the male reproductive tract and glands come from fetal Wolffian ducts. The research which led to these findings was the results of pioneer experiments by Alfred Jost.
   
   
4. The Mullerian duct will develop without hormonal stimulation and gives rise to oviduct, uterus, cervix and portions of vagina.
   
   
5. The Wolffian duct will regress unless stimulated by testosterone to develop into the vas efferentia, epididymis, vas deferens, and seminal vesicles.
   
   
6. In males, Mullerian duct regression is caused by MIS that is produced by the Sertoli cells.
   
   
7. In males the development of the prostate, Cowper's gland, penis, scrotum and descent of the testis is dependent on the presence of testosterone and its conversion within cells of these tissues into dihydrotestosterone.
   
   
8. In females, the formation of the distal portion of the vagina, labia and clitoris is not under hormonal control. The presence of female sex hormones is not required for these structures to develop. The embryonic and fetal tissue that gives rise to these structures will however be converted into male accessory sex glands, penis and scrotum if exposed to testosterone.

D. Phenotypic Sex:

1. The control of external genitalia formation is described above.
   
   
2. The remaining outward appearances that identify an individual as female or male are developed in the male in response to testosterone and its conversion to dihydrotestosterone in the target tissue. These characteristic can be altered, depending on the stage of development when testosterone is added or removed. Castration of males for example will alter body size, fat deposition and behavior if done early in life. Female appearance will occur in the absence of sex steroids but is enhanced by estrogen exposure.
   
   
3. XY males without receptors for testosterone have inguinal testis and their external appearance is female, but are non-cyclic, non-fertile women - called testicular feminization syndrome.

E. Brain and Behavioral Sex:

1. Early imprinting by hormone affects later brain control of reproduction through both GnRH release patterns (different in males and females) and in behavior as well.
   
   
2. Examples of Brain Sex
   
   
   1. female rat - testosterone injected at birth, never cycles and not fertile.
      
      
   2. A dimorphic sex center exists in the brain that is programmed by prenatal sex hormones to develop masculine (i.e., testosterone) or feminine (i.e., no testosterone) sex behavior patterns. This is present not only in animals but in humans as well and is now believed to not only control patterns of GnRH release but leads to gender identification and sexual orientation as well (heterosexual vs. homosexual).
      
      
3. Examples of Behavioral Sex:
   
   
   1. The behavior of male domestic animals is often dangerous or objectionable (pets). Castration results in a more docile animal.
      
      
   2. Testosterone given to a cow will produce behavior of a bull.
      
      
   3. Libido is affected by sex steroids.