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1. GAMETES, WHERE DO THEY COME FROM? https://alphascientists.securesites.com/embryology_images/sperm1.html https://alphascientists.securesites.com/embryology_images/sperm1.html http://www.erin.utoronto.ca/~w3bio380/Lectsked/Lect04/Egg2.htm

2. Three different levels on which this question can be discussed. 1. Organismic - in the adult organism, what organs give rise to the gametes. 2. Ontogenetic/embryonic - What portion of the developing embryo gives rise to the gametes. 3. Historical/developmental - What is transferred from one generation to the next that constitutes the line of cells that forms the gametes.

3. testis scrotum Corpus spongiosum

4. Tubuli recti Human male reproductive tract

5. testis scrotum Corpus spongiosum

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7. Corpus spongiosum

9. What causes an erection at the physiologic level? 1. Sexual arousal ---> action potentials along nerve to corpora cavernosa and spongiosum ---> stimulate NANC (NonAdrenergic NonCholinergic) nerve cells to produce nitric oxide. 2. Nitric oxide enhances synthesis of the enzyme guanylate cyclase in tissues of the corpora. 3. Guanylate cyclase causes production of cyclic guanosine monophosphate (cyclic GMP) ---> a. Cyclic GMP causes relaxation of smooth muscle in aterial walls of the corpora ---> b. Results in increased blood flow into blood sinuses of the corpora ---> c. Causes erection by engorgement and swelling of sinuses as they fill with blood ---> d. Engorgement produces pressure against the veins in the corpora that greatly reduces the loss of blood from these tissues thus increasing the erection. 4. Once sexual arousal is lost (e.g. after ejaculation) the action potentials stimulating the production of cyclic GMP stop ---> a. Cyclic GMP remaining in the corpora tissues is degraded by phosphodiesterase (PDE) ---> b. This results in contraction of the arterial smooth muscles within the corpora and a loss of engorgement as the pressure blocking the venous blood flow is relieved, thus resulting in loss of the erection.

10. How does Viagra work? Viagra (sildenifil citrate) blocks the active site on the enzyme phosphodiesterase (PDE). Thus, in men with erectile disfunction caused by insufficient cyclic GMP, Viagra prevents PDE from breaking down the cyclic GMP. As a result, when a male is sexually aroused cyclic GMP can accumulate in the corpora and cause an erection. This might be a problem if all PDE in your body was shut down. However, there are 11 different types of PDE and in the corpora of the penis, PDE5 causes the breakdown of cyclic GMP. Viagra only blocks the activity of PDE5. Cialis and Levitra work the same way.

13. The Menstrual Cycle Approximately every 28 days between puberty and menopause in the human female - however, there is variation Consists of: 1. Menses days 0-5 2. Follicular or proliferative phase days 5-15 3. Secretory or luteal phase days days 15-28 Ovulation day 14 or 15

14. Menstrual Cycle - Players in the game: Organs: 1. Brain - supraoptic and paraventricular nuclei of the hypothalamus, median emminence 2. Pituitary gland - pars nervosa, pars distalis 3. Ovary - developing follicles, corpus luteum 4. If pregnancy occurs, the uterus and the embryo Major Hormones: 1. Glycoproteins - follicle stimulating hormone (FSH), luteinizing hormone (LH) 2. Steroids - estrogen(estradiol, est), progesterone (pro) 3. Peptides - gonadotrophic releasing hormone (GnRH), chorionic gonadotropin (HCG, BCG, etc.)

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19. Male reproductive cycle Hormonal Control of Spermatogenesis (Major hormones) 1. Hypothalamus secretes GnRH 2. GnRH stimulates gonadotrophs in pituitary to secrete FSH and LH 3. LH stimulates interstitial cells Leydig to produce testosterone 4. Testosterone + FSH stimulate development of spermatocytes and maturation of sperm 5. Testosterone feeds-back to hypothalamus, inhibiting further release of GnRH (estrogen secreted by Sertoli cells may also be involved in GnRH inhibition) 6. Lack of GnRH causes decrease in LH and FSH 7. Feed-back inhibition keeps sperm levels constant

20. Other hormones involved in the regulation of the menstrual cycle and sperm production. Inhibin - secreted by sertoli cells in males and granulosa cells of the ovarian follicles in females In both it has the effect of decreasing FSH secretion by the gonadotrophs. In males, inhibin is also involved in regulating testosterone secretion - decreases it Assay of inhibin A concentrations in the blood during pregnancy is part of the “Quad Test” or “Quad screen” (used to be the “Triple Test”) This test measures the concentrations of inhibin A, estriol, beta - HCG, and alpha-fetoprotein. Elevated inhibin A Elevated beta-HCG Reduced estriol Reduced alpha-fetoprotein suggests the possibility of Down’s syndrome. In such cases, more definitive tests will be done.

21. Ontogenetic/embryonic - where do gametes arise from in the embryo? Amphibians 8 cell stage, vegetal view Stage 26 tadpole Stage 37 tadpole Xpat at vegetal pole Xpat cells at genital ridges Xpat cells in tail endoderm Xpat - Xenopus primordial germ cell associated transcript http://www.imolbio.oeaw.ac.at/xenopus/Marker_pages/germ/Xpat.html zygote

22. Origin of primordial germ cells in primates, including humans It is now known that the PGCs of mammals originate in the outside tissue layer of the early embryo (epiblast) and then migrate to the endoderm of the yolk sac. They then migrate via the circulatory system to the genital ridge.

23. Historical/developmental - What is transferred from one generation to the next that constitutes the line of cells that form the gametes? Germ plasm theory - August Weismann 1893 Recognized the difference between somatic and germ cells. Since only germ cells could pass on hereditary information to the next generation, Weismann proposed his “Germ plasm Theory,” i.e. that a germ plasm that was responsible for inherited characteristics was passed from generation to generation via the germ cells. This was before the function of DNA was understood. A germ plasm of a sort is formed as the result of gene activity that causes the synthesis of RNAs that specify primordial germ cell differentiation. In some species, such as amphibians, these RNAs are segregated into a specific group of cells during cleavage and these cells form the primordial germ cells. In other species (e.g., mammals) unkown factors cause the genes that specify primordial germ cells to turn on at a later point in development. The germ cell line forms the thread of continuity between generations.

24. SHADES OF GRAY ? Sexual Differentiation Male? Female? ABSOLUTES Or

25. What is sex? How is it determined? What are the characteristics that define a person’s sex? At the molecular level - Genotype At the organismal level Phenotype Behavior How do we (you and I) determine a person’s sex? Phenotype Behavior

26. What is sex? How is it determined? What ultimately determines sexual phenotype? Is the XX or XY genotype the only determining factor? No What are the various types of sexual behavior in terms of human-human interactions? Heterosexual Homosexual Bisexual Asexual What sorts of things affect a person’s sexual behavior? Genotype Phenotype Hormones Social/cultural Factors

27. In humans, up to the 7th week of gestation male and female embryos are identical. Rudiments of both the male and female reproductive systems are present. Changes that will determine whether an embryo will be male or female begin at the 7th week of gestation. Default differentiation is female. So, what determines whether an embryo is male or female? The SRY gene - Peter Goodfellow and Robin Lovell-Badge (1990) SRY - Sex determining Region of the Y chromosome

30. Is it really that simple? Usually, but not always. Do XX and XY always determine a person’s genetic sex? No! On rare occasions the SRY gene is on the X chromosome (i.e XX can sometimes be male) or the SRY gene on the Y chromosome is missing or defective and non-functional (i.e. XY can sometimes be female). Does the presence or absence of a functional SRY gene and the results of its activity always determine a person’s sex?

31. Genetic sex - YES! Phenotypic sex - NO! The presence or absence of hormones and their effects on tissues are critical for determining phenotypic sex!

32. Testosterone 5α−dihydrotestosterone 5α-ketosteroid reductase Genital tubercle, genital swellings give rise to the penis and the scrotal sac in males. Testosterone and dihydrotestosterone dependent male structures

33. Androgen insensitivity syndrome (AIS) Catch-all term that is used for conditions where, for whatever reason, in genetically male embryos, the tissues that form male genitalia don’t respond to 5α-dihydrotestosterone. Examples: XY testicular feminism Defect in the cytoplasmic receptor for 5α-dihydrotestosterone Has effect on cells of the genital tubercle and genital swellings 5a-ketosteroid reductase deficiency Defect in the enzyme that converts testosterone into 5α-dihydrotestosterone. It’s not as efficient in converting the testosterone.