Reproduction

Question 1

Cell Cycle

Answer 1

• In humans, autosomal cells are said to be Diploid (2n), meaning they have 46 individual chromosomes arranged into 23 pairs; and germ cells are said to be Haploid (n), meaning they have only 23 individual unpaired chromosomes.

• Cell cycle regulated by CDK molecules (cyclin-dependent kinases) and cyclin. Cyclin levels fluctuate throughout cell cycle, and when cyclin binds to CDK, an activated CDK-cyclin complex is formed which can phosphorylate transcription factors that promote transcription of genes required for next stage of cell cycle.
• Cell cycle of actively dividing cells consists of four stages (G1, S, G2, M).
• Interphase consists of G1, S, G2, and is the longest part of the cell cycle; individual chromosomes exist in less condensed Chromatin form during interphase to make DNA available to RNA polymerase for transcription and thus cannot be seen using light microscopy.
• Mitosis and Cytokinesis is M phase of cell cycle; DNA is condensed into tightly coiled chromosomes to avoid losing any genetic material during cell division.
• Non-dividing cells spend all of their time in G0 Stage (an offshoot of G1 in which cell is simply living and carrying out its functions without any preparation for division).
• G1 Stage (Presynthetic Gap): Cell increases in size and creates mitochondria, ribosomes, endoplasmic reticulum for energy and protein production.
• Restriction Point: G1/S checkpoint governed by p53 protein that allows cell to move from G1 to S if condition of DNA is good enough for synthesis. If DNA is damaged, cell cycle is arrested until DNA is repaired.
• S Stage (Synthesis): Cell replicates DNA such that each chromosome consists of two identical Chromatids bound at Centromere. Ploidy does not change but cell entering G2 contains twice as DNA than it did in G1 (92 sister chromatids but still 46 individual chromosomes organized into 23 Homologous Pairs).
• G2 Stage (Postsynthetic Gap): Cell continues to grow, finishes making organelles and proteins, and reorganizes its contents to prepare for mitosis.
• G2/M Checkpoint: Checkpoint governed by p53 in which cell ensures it has achieved adequate size (enough cytoplasm) and the organelles have been properly replicated to support two daughter cells. Cell also checks that DNA replicated in S Stage was replicated properly without error.
• M Stage (Mitosis and Cytokinesis): Mitosis consists of Prophase, Metaphase, Anaphase, Telophase; Cytokinesis is the splitting of the cytoplasm and the organelles between two daughter cells.

• Derangement from cell cycle leads to cancer. Often occurs due to mutation of gene that produces p53. Tumors are created through rapid cell division. Metastasis occurs when cancerous cells produce factors that either digest basement membranes or encourage blood vessel formation and then spread to other parts of the body through the bloodstream or lymphatic system.

Question 2

Mitosis

Answer 2

• Occurs only in Somatic Cells (cells that are not involved in sexual reproduction) and results in two genetically identical daughter cells.

• Prophase: Chromatin condenses into chromosomes. Centrioles in the centrosome migrate to opposite poles of the cell and form Spindle Apparatus. Centrosome is a Microtubule Organizing Center of the cell; microtubules can extend toward the middle of cell or form Asters to anchor the centrioles to the cell membrane. Nuclear membranes dissolves, allowing spindle fibers to attach to the centromere of chromosomes via kinetochore proteins. Nucleoli becomes less distinct or may disappear.
• Metaphase: Chromosomes are aligned at the Metaphase Plate, equidistant form the two poles of the cell.
• Anaphase: Centromeres split so that each chromatid has its own centromere, allowing sister chromatids to separate via the shortening of kinetochore fibers.
• Telophase: Spindle apparatus disappears, nuclear membrane reforms, and nucleoli reappears. Chromosomes uncoil into chromatin form. Each of the two nuclei receive an identical copy of the original genome.
• Cytokinesis: Occurs at the end of telophase, and is the separation of the cytoplasm and organelles to give each daughter cell enough material to survive.

Question 3

Meiosis

Answer 3

• Occurs only in Gametocytes (germ cells) and results in up to four nonequivalent nonidentical daughter cells.

• Mitosis consists of one round each of replication and division, whereas Meiosis consists of one round of replication followed by two rounds of division.
• Meiosis I (Reductional Division) involves separation of homologous chromosomes to produce haploid daughter cells; Meiosis II (Equational Division) involves separation of sister chromatids without change in ploidy in a similar manner to mitosis.

• Prophase I: Chromatin condenses into chromosomes, spindle apparatus forms, and nucleolus and nuclear membrane disappear. Homologous chromosomes in a Homologous Pair (existing as 4 sister chromatids of 2 individual chromosomes) come together and intertwine in a process called Synapsis to form a Tetrad (four intertwined sister chromatids) held together by Synaptonemal Complex proteins at a contact point called the Chiasma. Chromatids of homologous chromosomes may break at the chiasma and exchange equivalent pieces of DNA in a process called Crossing Over (Single Crossovers or Double Crossovers); sister chromatids of the same chromosome do not cross over. Such genetic Recombination can unlink linked genes and serves to increase genetic variability and diversity. Crossing over produces daughter cells with unique pool of alleles (genes coding for alternate forms of a given trait) and explains Mendel’s Second Law of Independent Assortment (inheritance of one allele has no effect on the likelihood of inheriting certain alleles for other genes). Linkage violates Mendel’s Second Law.
• Metaphase I: Tetrads line up at metaphase plate and each chromosome in homologous pair attaches to a separate spindle fiber by its kinetochore (as opposed to each chromosome being held by two spindle fibers, one from each pole, in mitosis).
• Anaphase I: Homologous pairs are separated and pulled to opposite poles of the cell in process called Disjunction, which accounts for Mendel’s First Law of Segregation. Each chromosome of paternal origin disjoins from its homologue of maternal origin.
• Telophase I: Nuclear membrane reforms around each homologue (consisting of two sister chromatids joined at centromere). Cytokinesis results in two haploid intermediate daughter cells with random distribution of homologous chromosomes to each.
• Interkinesis: Short rest period between Meiosis I and Meiosis II during which chromosomes partially uncoil.
• Prophase II: Nuclear envelope dissolves, nucleoli disappear, centrioles
migrate to opposite poles, and spindle apparatus forms.
• Metaphase II: Chromosomes line up at metaphase plate.
• Anaphase II: Sister chromatids separate at centromere and are pulled to opposite poles by spindle fibers.
• Telophase II: Nuclear membrane forms around each new nucleus, and cytokinesis produces up to four daughter cells each containing only one sister chromatid.

Question 4

Sex Chromosomes

Answer 4

• Biological sex determined by 23rd pair of chromosomes (XX being female, XY being male).
• Ova can carry only X chromosomes; sperm can carry either X or Y.
• Sex-linked disorders are X-linked (and often recessive), as X chromosome carries sizable amount of genetic information. Males (XY) are Hemizygous for genes on X chromosome and will express disease-causing allele on X chromosome. Females (XX) can be homozygous or heterozygous for genes on X chromosome; females homozygous for disease-causing allele will express disease and females heterozygous for disease-causing allele are called Carriers.
• Y chromosome contains SRY (sex-determining region Y) gene responsible for formation of male gonads; absence of Y chromosome leads to female zygote.

Question 5

Male Reproductive System

Answer 5

• Functional components of Testes are highly coiled Seminiferous Tubules (where sperm are produced) and Interstitial Cells of Leydig (secrete testosterone and androgens). Sertoli Cells nourish sperm in Seminiferous Tubules.
• Spermatogenesis occurs in seminiferous tubules. Spermatogonia (diploid stem cells) develop into diploid Primary Spermatocytes after S Phase. Meiosis I produces haploid Secondary Spermatocytes. Meiosis II generates haploid Spermatids, which mature into Spermatozoa. Spermatogenesis results in four functional sperm per spermatogonium. Sperm consists of acrosome (used to penetrate ovum), head (holds genetic material), midpiece (contains mitochondria), and flagellum.
• Sperm produced in seminiferous tubules are passed to Epididymis, where sperm gain motility and are stored until ejaculation. During ejaculation, sperm travel through Vas Deferens into Ejaculatory Duct. The two ejaculatory ducts fuse to form Urethra, which carries sperm through Penis. Sperm mixed with Seminal Fluid produced by Seminal Vesicles, Prostate Gland, and Bulbourethral Glands. Seminal Fluid contains fructose to nourish sperm and is alkaline to counteract acidity of female reproductive tract. Sperm + Seminal Fluid = Semen.
• Male reproductive and urinary systems share common pathway.

Question 6

Female Reproductive Anatomy

Answer 6

• Ovaries produce estrogen and progesterone; each ovary contains thousands of Follicles, which are multilayered sacs that hold, nourish, and protect immature Ova (eggs). Between puberty and menopause, Ovulation occurs once per month, in which an ovum is released from ovary into Peritoneal Sac lining the abdominal cavity and then drawn into Fallopian Tube by its Fimbriae. Fallopian tubes connects to muscular Uterus (site of implantation and fetal development). Cervix (lower end of uterus) connects to Vaginal Canal and then Vagina. External female anatomy called Vulva.
• Oogenesis occurs in ovaries. All Oogonia are formed during fetal development (in contrast to unending supply of spermatogonia stem cells in males). By birth, oogonia have already undergone S Stage DNA replication and have developed into diploid Primary Oocytes what are arrested in Prophase I. Once Menarche (first menstrual cycle) is reached, one Primary Oocyte per month completes Meiosis I to produce Secondary Oocyte and Polar Body due to unequal cytokinesis. Secondary Oocyte remains arrested in Metaphase II until fertilization. Meiosis II completes when a sperm cell penetrates outer Corona Radiata and inner Zona Pellucida surrounding Secondary Oocyte using acrosomal enzymes, forming mature Ovum and another polar body. Haploid Pronuclei of sperm and ovum join to create diploid Zygote.
• Females have separate reproductive and urinary tracts.

Question 7

Sexual Development

Answer 7

• After puberty, hypothalamus releases pulses of GnRH (gonadotropin-releasing hormone), which stimulates Anterior Pituitary Gland to release FSH (follicle-stimulating hormone) and LH (luteinizing hormone).
• Males: FSH stimulates Sertoli Cells and triggers sperm maturation. LH stimulates Interstitial Cells to increase production of testosterone. Testosterone develops and maintains male reproductive system and leads to development of Secondary Sexual Characteristics (facial/axillary hair, deepening of voice, increased muscle and bone mass). Testosterone exerts negative feedback on hypothalamus and anterior pituitary to regulate its levels.
• Females: FSH stimulates ovarian follicle to grow and produce estrogen. LH stimulates Corpus Luteum (remains of follicle after ovulation) to secrete progesterone. Estrogen develops and maintains female reproductive system and leads to development of Secondary Sexual Characteristics (breast growth, widening of hips, changes in fat distribution). Estrogen responsible for thickening of Endometrium (uterine lining), but Progesterone responsible for maintenance of Endometrium. Corpus Luteum atrophies during pregnancy as placenta takes on responsibility to produce progesterone. Estrogen exerts negative feedback on hypothalamus and anterior pituitary to regulate its levels.

Question 8

Menstrual Cycle

Answer 8

• Occurs every month from menarche to menopause. Divided into four events: Follicular Phase, Ovulation, Luteal Phase, Menstruation.

• Follicular Phase: Begins with Menstrual Flow in which uterine lining from previous cycle is shed. GnRH secretion from hypothalamus increases due to drop in concentrations of estrogen and progesterone (which happens at end of each cycle). GnRH increases secretion of FSH and LH. FSH prepares follicle for ovulation and stimulates it to produce estrogen, which reduces GnRH, FSH, LH concentrations via negative feedback effects and triggers proliferative stage of endometrium (hypertrophy, vascularization, and glandularization of functional layer).
• Ovulation: Higher and higher levels of estrogen are released by the follicle until a threshold is reached that paradoxically exerts positive feedback on GnRH, increasing levels of FSH and LH. LH surge induces ovulation of ovum into peritoneal cavity of abdomen.
• Luteal Phase: LH causes ruptured follicle to turn into corpus luteum, which increases progesterone levels. Progesterone maintains the endometrium for implantation in its secretory stage, continuing hypertrophy, vascularization, and secretion. High progesterone concentration exerts negative feedback on GnRH, FSH, LH to prevent multiple ovulations.
• Menstruation: If implantation does not occur, corpus luteum loses stimulation from LH and atrophies, which causes decline in progesterone levels and triggers menses (sloughing off of uterine lining). Drop in progesterone and estrogen removes block on GnRH and LH and FSH levels rise, allowing cycle to begin again.
• If fertilization has occurred, resulting zygote will develop into blastula and implant in uterine lining. Chorion/placenta secretes hCG (human chorionic gonadotropin, an analogue of LH). hCG maintains corpus luteum, which allows it to continue secreting progesterone and estrogen for the maintenance of the uterine lining. By second trimester, hCG levels drop as placenta begins secreting estrogen and progesterone on its own. The high levels of estrogen and progesterone continue to serve as negative feedback on GnRH secretion.
• Menopause occurs when ovaries become less sensitive to FSH and LH and atrophy, leading to drop in estrogen and progesterone levels, atrophy of endometrium, and cessation of menstruation. Removal of negative feedback on FSH and LH causes the rise of FSH and LH levels in the blood. Menstruation accompanied by hot flashes and irritability.