The Reproduction System

Cell Cycle and Mitosis

• Autosomal cell are diploid (2n) and Germ cells are haploid (n). In humans these numbers are 46 and 23 respectively. Eukaryotic cells replicate through the cell cycle

The Cell Cycle

• Consists of four stages: G1, S, G2 and M. The first three are known as the interphase and this phase is the longest part of the cell cycle. Cells that are simply living and are not preparing for division are in the G₀ stage, which is an offshoot from G1. During the interphase cannot see chromosomes since they are in less condensed chromatin.

G1 Stage: Presynthetic Gap

• Cells create organelles for energy and protein production (mitochondria, ribosome and endoplasmic reticulum production), while also increasing in size.
• Movement into the S-Phase is governed by a restriction point
  • Criteria such as containing the proper complement of DNA must be passed

S Stage: Synthesis of DNA

• Cell replicated genetic information so that each daughter cell will have a full set.
  • Each chromosome consists of two identical chromatids which are bound together at the
  • Ploidy (sets of chromosomes) does not change during this process.
    • Still only contain 46 chromosomes but have 92 chromatids.

G₂ Stage: Postsynthetic Gap

• Cells entering have twice as much DNA as cells in G₁
• Cells pass through another quality control checkpoint
  • Cells check if there are enough organelles and cytoplasm to divide
  • Checks to see make sure that DNA replication proceeded correctly.

M Stage: Mitosis

• Consists of mitosis along with cytokinesis (splitting of cytoplasm and organelles into two daughter cells). Mitosis has four phases: prophase, metaphase, anaphase, telophase

Control of the Cell Cycle

• Controlled by the checkpoints between the G₁/S phase and the G₂/M phase.
• During G_1/S, the cell determines if the DNA is good enough for synthesis.
  • Known as restriction points since cell cycle will not continue until DNA is fixed
    • Main protein involved is p53
• At the G₂/M, cell is concerned with ensuring there is enough organelles and has adequate size to be able to split into two daughter cells. Also use p53
• Cyclins & Cyclin-dependent kinases (CDK): molecules responsible for cell cycle.
  • CDK’s need presence of right cyclins to be activated. During cell cycle, the concentration of cyclins increases or decreases. The cyclins bind to the CDK to created active complexes.
    • Complex then phosphorylates transcription factors
  • Transcription Factors: promote transcription of genes required for next stage of cell cycle.
• Cancer: may result when cell cycle control becomes deranged and damaged cells are allowed to undergo mitosis.
  • One of the most common mutations in cancer is a mutation of the gene, TP53, which produces p53. Thus the cell cycle is not stopped to repair damaged DNA.
  • Mutation accumulate and sometimes undergo rapid cell division to form Tumors.
  • Metastasis is when there is a distant spread of cancerous cells through the bloodstream or lymphatic system.
  • If cell produces right factors, can reach other tissues

Mitosis

• Process by which two identical daughter cells are created from a single cell.  Occurs in Somatic cells (not involved in sexual reproduction).
• Prophase: first step in mitosis
  • Condensation of the chromatin into chromosome occurs first
  • Centriole pairs separate and move towards opposite poles of cell
    • Centrosome is the location of paired cylindrical organelles (centrioles) which are responsible for the correct division of DNA.
  • Spindle Fibers: begin forming when centrioles move to opposite poles. Are made of microtubules
    • The centrosome and basal body (of flagellum or cilium) are known as the microtubule organizing centers of the cell
    • Each fiber radiations outward from centriole
      • Asters are formed microtubules which anchor the centriole to the membrane.
    • Other fibers radiate towards the center waiting for the nuclear membrane to dissolve so that they can contact the chromosomes
  • Nuclear membrane dissolves and nucleoli become less distinct.
    • Exposure of genetic information
  • Kinetochore are protein structures that serve as attachment points for specific fibers of spindle apparatus, called kinetochore fibers. Appear at the centrosome.
• Metaphase: Centriole pairs are at opposite ends of the cell. Kinetochore fibers interact with fibers of spindle apparatus to align chromosomes at the metaphase (equatorial) plate.
• Anaphase: centromeres split which allows sister chromatids to separate and be pulled towards opposite poles of the cell by the shortening of kinetochore fibers.
• Telophase & Cytokinesis
  • Telophase is reverse of prophase: the spindle apparatus disappears. Nuclear membrane reforms, nucleoli reappear, chromosomes uncoil into chromatin.
  • Cytokinesis occurs at end of telophase.
    • The separation of cytoplasm and organelles so that each daughter cell has sufficient supplies to function appropriately.
  • Each cell has finite number of divisions before death (usually 20-50)

Meiosis

• Occurs in gametocytes (germ cells) and can result in up to four non-identical sex cells, gametes. Shares similarities with mitosis: duplication of genetic info, chromatin condensing into chromosomes, and microtubules emanating from centrioles are involved.
• Consists of one round of replication and then two rounds of division (**different from mitosis which has one round each**)

Meiosis I

• Known as reduction division since it creates haploid daughter cells from homologous chromosomes being separated.
• Human genome has 23 homologous pairs of chromosomes, which means that each pair contains one chromosome inherited from each parent. After S phase there are 92 chromatids organized into 46 chromosomes which are organized into 34 homologous pairs.

Prophase I

• Chromatin condenses into chromosomes, spindle apparatus forms, and nucleoli and nuclear membrane disappear.
• Synapsis is first major distinction. Where homologous chromosomes come together and intertwine.
  • Each chromosome has two sister chromatids, so in total there are four chromatids in a synaptic pair which is called a tetrad.
  • Homologous chromosomes held together by group of proteins called synaptonemal complex
• Crossing Over: where chromatids may break at chiasma and subsequently exchange equivalent pieces of DNA.
  • Characterized by number of events that occur in one strand.
  • Chromatids are left with an altered but structurally complete set of genes.
  • Results in genetic recombination can unlink genes which results in an increased variety of genetic combinations.
  • Each daughter cell will have a unique pool of alleles which formed from a random mixture of maternal and paternal origin.
    • This explains Mendel’s Second Law of Independent Assortment: states that the inheritance of one allele has no effect on the likelihood of inheriting certain alleles from other genes.
• Linkage is the tendency of genes to be inherited together. The further apart the genes are, the less likely the linkage is.

Metaphase I

• Homologous pairs (tetrads) align at metaphase plate. Each pair attaches to a separate spindle fiber by its kinetochore.
• Difference from mitosis since each homologous chromosome pair is held by one spindle fiber on opposite sides (no splitting of centromere in this step)

Anaphase I

• Homologous pairs separate and pulled towards opposite poles. Process is called disjunction and accounts for Mendel’s First Law.
• Each chromosome from paternal origin separates from its homologue of maternal origin, and can end up in either daughter cell. Thus, distribution of chromosomes is random with respect to parental origin. Process of separating two homologous chromosomes is known as Segregation.

Telophase I

• Nuclear membrane forms around each new nucleus. Cells are now haploid.
• Cell divides into two daughter cells by cytokinesis. May have a short rest period known as interkinesis, chromosomes slightly uncoil during this phase.

Meiosis II

• Prophase II: nuclear envelope dissolves, nucleoli disappear, centrioles migrate to poles and spindle apparatus begins to form.
• Metaphase II: chromosomes line up at metaphase plate
• Anaphase II: centromeres divide which separate chromosomes into sister chromatids.
• Telophase II: nuclear membrane forms around each new nucleus and cytokinesis follows. Two daughter cells are formed per daughter cell formed in Meiosis I. Thus up to four daughter cells are produced per gametocyte.

The Reproductive System

• Biological sex is determined by the 23^rd pair of chromosomes. XY is male and XX is male, ovum’s only carry X while sperm can carry both.
• X chromosomes: carry a lot of genetic information. Mutations in these genes can cause sex-linked
  • Hemizygous: means that you only have one copy of gene. Males are termed this. Makes them higher risk since a disease carrying allele cannot be suppressed
  • Heterozygous or Homozygous: females are this since they have two X chromosomes. Females express sex-linked disorders far less frequently since they are usually recessive. Are termed carriers if they carry diseased allele but do not exhibit the disease.
• Y Chromosome: subsequently: little genetic information other than sex determining region Y (SRY).

Male Reproductive Anatomy

• Primitive gonads develop into testes. Which have two functional components: the seminiferous tubules and the interstitial cells.
• Sperm is produced in the highly coiled tubules where they are nourished by Sertoli Cells
• Cells of Leydig (interstitial) secrete testosterone and other male sex hormones (androgens).
• Testes located in Scrotum: an external pouch that hangs below penis.
• As sperm is formed, it passes through the epididymis (flagella gain motility) and are then stored until ejaculation.
• During ejaculation, sperm travels through the Vas deferens to the ejaculatory duct at the posterior edge of the prostate gland. Two ducts then form the urethra.
• As sperm passes through reproductive tract, it is mixed with seminal fluid (produced by seminal vesicle, prostate gland, and bulbourethral gland).
  • Seminal Vesicle contribute fructose to nourish sperm
  • Prostate Gland and seminal vesicle provide sperm with alkaline properties
  • Bulbourethral (Cowper’s) Gland produce clear viscous fluid that cleanses out and remnants of urine and provides lubrication.
• Semen: combination of sperm and seminal fluid

Spermatogenesis

• Is the formation of haploid sperm through meiosis, and it occurs in the seminiferous tubules.
• Spermatogoinia: diploid half cells in males. After S stage are known as diploid primary spermatocytes. After first meiotic division are known as haploid secondary spermatocytes. After meiosis II, are known as spermatids. These develop into mature spermatozoa.
• Four functional sperm results from each spermatogonium
• Sperm consists of:
  • Head: contains genetic material. Covered by acrosome cap which is needed to penetrate the ovum.
  • Midpiece: filled with mitochondria which generates ATP from fructose
  • Flagellum: used for movement

Female Reproductive System

• All organs are internal. Gonads are known as ovaries which produce estrogen and progesterone.
  • Ovaries are located in pelvic cavity which consist of thousands of follicles
• Follicles: multilayered sacs that contain, nourish and protect immature Ova
• Only one egg is ovulated per month into the peritoneal sac. It is then drawn into the fallopian tubes (or oviduct).
  • Oviduct is lined with cilia to propel ovum forward
  • Tubes connected to Uterus
• Uterus is the site of fetal development. Lower end is known as the cervix and it is connected the vaginal canal.
• Vulva: external female anatomy.

Oogenesis

• Production of female gametes. There is no unending supply of stem cells, all oogonia a woman will ever have been formed during fetal development.
• Primary oocytes: By birth all oogonia have undergone DNA replication and are considered this. Are 2n and arrested in prophase I.
• Secondary oocyte: once a woman reaches her first menstrual cycle (menarche), one primary oocyte completes meiosis I. this produces a secondary oocyte and a polar body.
  • Characterized by unequal cytokinesis. Ample cytoplasm given to secondary oocyte, but barely any to the polar body.
  • The polar body usually does not divide anymore and will never produce gametes.
  • The secondary oocyte remains arrested in metaphase II unless fertilization occurs.
• Oocytes are surrounded by two layers
  • Zona pellucida: surrounds the ooycyte itself and is an acellular mixture of glycoproteins that protect and contain compounds for sperm binding
  • Corona Raiata: lies outside zona and is a layer of cells that adhered to cell during ovulation.
• Meiosis II is triggered when a sperm cell penetrates these two layers. The 2ndary oocyte breaks down into another a mature ovum and another polar body.
• A mature ovum is a very large cell since it contributes all organelles, cytoplasm, half the DNA, RNA and physical space for the Zygote.
• Completion of meiosis II is when the haploid sperm and ovum nuclei join to create a diploid zygote.

Sexual Development

• The hypothalamus restricts production of gonadotropin-releasing hormone (GnRH) before puberty. Release of GnRH triggers the anterior pituitary gland to synthesize and release follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Male Sexual Development

• Presence of Y chromosome leads to production of androgens during week 9 of fetal period. Androgen production is low for the duration of infancy and childhood.
• Testosterone, increases dramatically during puberty.
  • FSH triggers Sertoli cells and triggers sperm maturation
  • LH triggers interstitial cells to produce testosterone
  • develops and maintains male reproductive system and also results in the development of secondary sexual characteristics.

Female Sexual Development

• Estrogen: secreted in response to FSH and results in development and maintenance of female reproductive system and female secondary sexual characteristics.
  • In embryo: stimulates development of reproductive tract
  • In adult, thickens lining of uterus (endometrium) each month in prep for zygote
• Progesterone: secreted by corpus luteum which is the remnant follicle that remains after ovulation. Controlled by LH. Involved in development and maintenance of endometrium. Not in the creating of it.
  • Is later supplied by the placenta after the first trimester.

The Menstrual Cycle

• Follicular Phase: Begins when the menstrual flow (the shedding of the uterine lining) begins.
  • GnRH is secreted from the hypothalamus increases in response to the decreased concentration in estrogen and progesterone, which fall off towards end of cycle.
  • Causes increase secretion of FSH and LH. Which work together to develop several ovarian follicles.
    • The negative feedback of the follicles producing estrogen causes GnRH, LH, FSH concentration to level off.
  • Estrogen regrows endometrial lining by stimulating vascularization and glandularization of the decidua.
• Ovulation: Late in follicular phase, follicles secrete higher concentrations of estrogen which eventually reach a threshold that results in a spike of GnRH, FSH, and LH levels.
  • LH surge induces ovulation which is the release of the ovum from the ovary into the peritoneal cavity.
• Luteal Phase: After ovulation, LH causes corpus luteum to form from ruptured follicles. This secreted progesterone.
  • Progesterone levels begin increase while estrogen levels remain high.
  • Progesterone levels elevating cause negative feedback on LH, FSH, and GnRH which prevents ovulation of multiple eggs.
• Menstruation: If implantation does not occur, the corpus luteum loses stimulation, progesterone levels decline and the uterine lining is shed off.
  • Loss of estrogen and progesterone triggers more release of GnRH
• Pregnancy: if fertilization does occur, Zygote will develop into blastocyst that will implant in the uterine lining and secrete human chorionic gonadotropin (hCG).
  • hCG is analogous to LH, which helps in maintaining the corpus luteum, which helps in keeping the uterine lining in place by secreting estrogen and progesterone.
  • Once in 2^nd trimester, hCG because placenta has grown to sufficient size to secrete hormones on its own.
• Menopause: As woman ages, ovaries become less sensitive to LH and FSH which results in ovarian atrophy.
  • Endometrium eventually atrophies as estrogen and progesterone levels drop
  • Menopause is when there are elevated levels of LH and FSH in the blood