Sex determination and differentiation (human)
Encyclopedia
The Jost Paradigm
Under typical circumstances, the sexSex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
of an individual will be determined and expressed through the following mechanisms:
- Chromosomal Sex (genetic): Presence or absence of Y chromosomeChromosomeA chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
- Gonadal Sex (Primary Sex Determination): Controlled by presence or absence of testis determining factorTestis determining factorTestis-determining factor is a general term for the gene that results in maleness in humans and some other species.Certain genes cause chemical reactions that result in the development of testes...
(TDF) - Phenotypic Sex (Secondary Sex Differentiation): Determined by the hormonal products produced by the gonads.
Sex differentiation
Sex differentiation refers to the expression of phenotypic attributes specific to the sex of an individual. While gonad development is a result of the presence or absence of the sex determination gene SRY on the Y chromosome, sex differentiation is determined by the hormonal products produced by the gonads.Testosterone
In the 1930s, Alfred JostAlfred Jost
Alfred Jost was a French endocrinologist, famous for his discovery of the Mullerian inhibitor, now called anti-Mullerian hormone or Mullerian inhibiting substance...
determined that the presence of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
was required for Wolffian duct
Wolffian duct
The mesonephric duct is a paired organ found in mammals including humans during embryogenesis....
development in the
male rabbit.
Müllerian inhibiting substance
Jost also observed that while testosterone was required for Wolffian duct development, the regression of the Müllerian ductMüllerian duct
Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in...
was due to another substance. This was later determined to be Müllerian inhibiting substance (MIS), a 140 kD dimeric glycoprotein that is produced by sertoli cells. MIS blocks the development of Müllerian ducts, promoting their regression.
5-alpha dihydrotestosterone (DHT)
Testosterone is converted to the more potent DHTDihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
by 5-alpha reductase. DHT is necessary to exert androgenic effects farther from the site of testosterone production, where the concentrations of testosterone are too low to have any potency. A 5-alpha reductase deficiency results in an androgen disorder characterized by female phenotype or severely undervirilized male phenotype with development of the epididymis
Epididymis
The epididymis is part of the male reproductive system and is present in all male amniotes. It is a narrow, tightly-coiled tube connecting the efferent ducts from the rear of each testicle to its vas deferens. A similar, but probably non-homologous, structure is found in cartilaginous...
, vas deferens
Vas deferens
The vas deferens , also called ductus deferens, , is part of the male anatomy of many vertebrates; they transport sperm from the epididymis in anticipation of ejaculation....
, seminal vesicle
Seminal vesicle
The seminal vesicles or vesicular glands are a pair of simple tubular glands posteroinferior to the urinary bladder of male mammals...
, and ejaculatory duct
Ejaculatory duct
-Anatomy:The ejaculatory ducts are paired structures in male anatomy. Each ejaculatory duct is formed by the union of the vas deferens with the duct of the seminal vesicle. They pass through the prostate, and open into the urethra at the Colliculus seminalis...
, but also a pseudovagina.
Pathologies
The following disorders are caused by a malfunction in the sex determination and differentiation process:- Congenital adrenal hyperplasiaCongenital adrenal hyperplasiaCongenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
- Inability of adrenal to produce sufficient cortisolCortisolCortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
, leading to increased production of testosterone resulting in severe masculinization of 46 XX females. - Persistent müllerian duct syndromePersistent Mullerian duct syndromePersistent Müllerian duct syndrome refers to the presence of a uterus and sometimes other Müllerian duct derivatives in a male animal...
- A rare type of pseudohermaphroditismPseudohermaphroditismPseudohermaphroditism, or pseudo-hermaphroditism, is the condition in which an organism is born with secondary sex characteristics or a phenotype that is different from what would be expected on the basis of the gonadal tissue ....
that occurs in 46 XY males, caused by either a mutation in the Müllerian inhibiting substance (MIS) gene, on 19p13, or its type II receptor, 12q13. Results in a retention of Müllerian ducts (persistence of rudimentary uterus and fallopian tubes in otherwise normally virilized males), unilateral or bilateral undescended testes and sometimes causes infertility. - Male pseudohermaphroditism - Failure of androgen production or inadequate androgen response, which can cause incomplete masculinization in XY males. Varies from mild failure of masculinization with undescended testes to complete sex reversal and female phenotype (Androgen insensitivity syndromeAndrogen insensitivity syndromeAndrogen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...
) - Swyer syndromeSwyer syndromeSwyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty...
. A form of complete gonadal dysgenesis, mostly due to mutations in the first step of sex determination; the SRYSRYSRY is a sex-determining gene on the Y chromosome in the therians .This intronless gene encodes a transcription factor that is a member of the SOX gene family of DNA-binding proteins...
genes.