Sex Differentiation & Gametogenesis

• Presentation covers sex differentiation and gametogenesis.
• Goals are to review cell division, fetal sex differentiation, hypothalamic defeminization, gametogenesis, estrous cycle control, fertilization, and maternal pregnancy recognition.

Cell Division Reminder

• Somatic cells contain pairs of homologous chromosomes.
• Each chromosome initially has one chromatid

Mitosis

• Chromatids separate during mitosis.
• Two diploid cells, each with 46 chromosomes and 46 chromatids are generated.
• Resulting cells are 2n & 2c.
• Two identical daughter cells are produced with no crossing over.

Meiosis

• A cell division form reduces the chromosome number.
• Creates four haploid daughter cells.
• Each cell is genetically distinct from one another.
• Crossing over occurs in Prophase I.
• During homologous recombination, chiasmata are not at random points.
• This introduces variation into sexual reproduction.

Meiosis I

• Homologous chromosomes separate.
• Two haploid cells are generated with 23 chromosomes but 46 chromatids.
• These generated cells are N & 2C.

Meiosis II

• Chromatids separate.
• Generate two haploid cells with 23 chromosomes and 23 chromatids.
• Resulting in N & C

Early Embryo Development

• Several mitotic divisions occur during the this phase.
• Divisions happen without an increase in cell mass; cleavage is also known as "Reduction Division".
• Maternal secretions provide metabolic support.
• Zygotic protein synthesis starts at the 2- to 16-cell stage, and cells during this stage are totipotent, depending on the species.
• Totipotent cells can give rise to any tissue.

Morula to Blastocyst Transition

• Differentiation from morula to blastocyst is an important event during embryo life.
• During the morula stage, cells differentiate into two groups.
• Inner cell mass (ICM) are polarized cells in the blastocyst, and will form the embryo.
• Trophoblast will develop the chorion (placenta - external portion).
• Trophoblast cells pump sodium into the intracellular space leading to water influx due to osmotic pressure, forming the blastocele.
• The blastocele will later become the yolk sac.

Embryology

• The embryo starts as a mass of cells that form layers and will differentiate into the embryo proper and placenta.

Placental Development

• The trophoblast is the external embryonic tissue giving rise to the chorion or the placenta.
• Extraembryonic mesoderm develops into the allantois.
• Expansion of the allantois and fusion with the chorion forms the allantochorion or the placenta.

Embryonic Sex Differentiation

• Genetic sex is determined by the zygote.
• Gonadal sex differentiation occurs around the 6th-8th week.
• Phenotypic sex occurs around the 12th week.
• Primordial germ cells migrate from outside the organism or the yolk sac, into the organism via the hindgut to the undifferentiated gonad, located within the dorsal body wall: also referred to as the genital ridge.
• In large domestic animals, the embryo is initially indistinguishable for about six weeks.
• Reproductive system development occurs simultaneously with the renal system.

Sex Differentiation

• Male sex is an XY chromosomal pair
• Female sex is an XX chromosomal pair
• Testis-determining factor (TDF) leads to the development of testes.
• Sertoli cells secrete anti-Müllerian hormone (AMH).
• AMH causes Leydig cells to differentiate.
• Males produce Testosterone, leading to the degeneration of the paramesonephric duct.
• Dihydrotestosterone then spurs the development of the male duct system, the penis, scrotum, and accessory sex glands.
• Females have no TDF leading to ovaries developing
• Paramesonephric ducts become the oviducts, uterus, cervix, and part of the vagina

Absence of factors lead to female differentiation

• Absence of the testis-determining factor
• Absence of AMH
• Absence of Testosterone

Hypothalamus Differentiation

• The female hypothalamus contains tonic and surge functional areas for Gonadotropin-releasing hormone (GnRH) secretion
• The hypothalamus is inherently female
• Testosterone during development defeminizes the brain
• Testosterone crosses the blood-brain barrier and is converted to Estradiol.
• Estradiol defeminizes the hypothalamus, eliminating the surge center.
• Fetal ovaries produce Estradiol, but this does not cross the blood-brain barrier due to its binding with alpha-fetoprotein.

Oocyte Development

• Most mammals are born with oogenesis starting at Meiosis I - Primary oocyte.
• Oocytes get arrested in prophase I until puberty, and cells during this are 2N and 4C.

Postnatal Oocyte Development

• The primary oocyte continues through Meiosis I and duplicates its DNA (Interphase), where the chromosomal complement is 2N & 4C occurs in prophase.
• Meiosis is then resumed at the ovulatory surge of Luteinizing hormone (LH) or puberty.
• Meiosis I results in a secondary oocyte (n & 2C) and a polar body that will degenerate.
• Polar bodies form after meiotic divisions.
• The polar body is important for reducing the genetic material, and polar bodies degenerate

Secondary Oocytes

• The secondary oocyte is the cell formed post meiosis I in oogenesis: has one of each homologous chromosome pair after crossing over.
• Each chromosome has two chromatids, making 46 chromatids (2C).
• It continues to the second stage of meiosis (meiosis II), but is arrested at metaphase II until sperm contact occurs in the fallopian tube.
• Ovulation occurs during the second meiotic division
• Meiosis II completes at the time of fertilization.
• Results in an ovum (n) and a polar body (will degenerate).

Ovulation

• The oocyte releases from the follicle.
• Oocyte and cumulus mass move to the infundibulum of the uterine tube by fimbriae.
• Meiosis continues post-fertilization, unless blocked at metaphase II Fertilization occurs in the ampulla of the uterine tube within a short window of 6-12 hours.

Fetal Life - Spermatogonium Development

• Primary germ cells originate near the yolk sac, migrating to the developing gonad that is the genital ridge.
• This then differentiates to spermatogonium and multiplies by mitosis, resulting into diploid cells (2N).
• Male mammals are born with spermatogonium that can undergo multiple mitosis.

Spermatogenesis Requirements

• Sperm function requires development and maturation through the testis and epididymis, which takes overall 60ish days.
• Requires temperature lower than body temperature at 34 °C or 93 °F.
• Requires hormones, specifically Testosterone.