Sex Determination

1. BIOL 370 – Developmental Biology Topic #17 Sex Determination Lange

2. Sex Determination is a biological process that determines development of sexual characteristics in an organism.

3. Sex determination in mammals (Part 1) Mammalian sex determination is the most common form….. XX  female XY  male But, this is by no means the only method of sex determination that is seen in sexually reproducing species…

4. 44 + XY 44 + XX Parents 22 + X 22 + XY 22 + Y Ova Sperm 44 + XY 44 + XX Zygotes (offspring) (a) The X-Y system 22 + XX 22 + X (b) The X-0 system 76 + ZW 76 + ZZ (c) The Z-W system 16 (Haploid) 32 (Diploid) (d) The haplo-diploid system Some chromosomal systems of sex determination

5. XY sex-determination: • the sex-determination system found in humans, most other mammals, some insects (including Drosophila), and some plants (Ginkgo). • Sex of an individual is determined by a pair of sex chromosomes (gonosomes). • Females have two of the same kind of sex chromosome (XX), and are called the homogametic sex. • Males have two distinct sex chromosomes (XY), and are called the heterogametic sex.

6. ZW sex-determination: • determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects (including butterflies and moths), and some reptiles, including komodo dragons. • In the ZW system, the ovum determines the sex of the offspring. • The letters Z and W are used simply to distinguish this system from the XY system. • Males are the homogametic sex (ZZ), while females are the heterogametic sex (ZW). • The Z chromosome is larger and has more genes, like the X chromosome in the XY system. • BUT…. a very interesting and odd exception is seen in: • Booth, W., Smith, C.F., Eskridge, P.H., Hoss, S.K., Mendelson, J.R., and Schuett, G.W., Facultative Parthenogenesis Discovered in Wild Vertebrates. Biol. Lett. (2012) 8, 983–985.

7. X-0 sex-determination: • Hymenopterans, grasshoppers, crickets, cockroaches, and some other insects determine the sex of their offspring via this method. • Only one sex chromosome, referred to as X is seen. • Males only have one X chromosome (X0). • Females have two (XX). • Maternal gametes always contain an X chromosome, so the sex of the animals' offspring is decided by the male. • Sperm normally contain either one X chromosome or no sex chromosomes at all.

8. In a variant of X-O sex determination, certain animals are actually hermaphroditic with two sex chromosomes (XX) and male with only one (X0). The model organism Caenorhabditis elegans— the nematode, one such organism.

9. Z-0 sex determination: • Seen in a few moth species. • males have two Z chromosomes. • females have one Z chromosome.

10. Haplodiploidy: • sex-determination system in which males develop from unfertilized eggs and are haploid. • females develop from fertilized eggs and are diploid. • Social insects display this sort of determination frequently. • An alternative name for haplodiploidy is arrhenotoky.

11. Temperature-Dependent Sex Determination (TSD): • a type of environmental sex determination • temperatures experienced during embryonic development determine the sex of the offspring • most prevalent and common among amniote reptile vertebrates • a type of environmental sex • eggs are affected by the temperature at which they are incubated during the middle one-third of embryonic development

12. The critical period of incubation is for TSD is known as the thermosensitive period (TSP): • Depending upon the species, TSP will last roughly 7-15 days. • Temperature must be maintained during this period for a certain sex to be determined

13. Temperature-dependent sex determination in three species of reptiles: the American alligator, red-eared slider turtle, and alligator snapping turtle

14. Until recently, it was thought that one bird species, the Australian Brush-turkey displayed temperature dependent sex determination. However, an article in Biological Letters has shown evidence that disproves the TDS method for the species: Goth, A., and Booth, D.T. 2005. Temperature Dependent Sex Ratio in a Bird. Biol. Lett. 1:31-33.

15. Sex determination in mammals (Part 2)

21. Figure 27.23

22. Differentiation of human gonads shown in transverse section (Part 1) In this variation from your textbook, the primary focal difference between week 4 and 6 in humans is the presence of the mullerian duct and the increased size of the genital ridge seen by week 6. Also at this time notice how the glomerulus is very intertwined with the Wollfian Duct system.

23. Differentiation of human gonads shown in transverse section (Part 2) When the male develops, this development becomes fixed by week 8 in normal development. Regression of the Mullerian system then begins as well in normal development. Notice how by week 8 the degeneration of the mesonephric tubule occurs.

24. Differentiation of human gonads shown in transverse section (Part 3) In female development, we see the Mullerian Duct system develop and the Wollfian degenerate. Notice how here we also see the degeneration of the mesonephric tubule in the female at week 8.

25. Development of the gonads and their ducts in mammals

26. Development of the gonads and their ducts in mammals (Part 1)

27. Development of the gonads and their ducts in mammals (Part 2)

28. Development of the gonads and their ducts in mammals (Part 3)

29. An XX mouse transgenic for Sry is male The mice shown here are male (left) and female (right). However, the female has male external genitalia due to the transgenic grafting of the Sry gene onto one of the X chromosomes in the female. Notice the Sry band she shows when we look at the blot profile.

30. Ability of Sox9 to generate testes Sox9 is a gene that encodes for a transcription factor protein that has been found to be critical for generating the testes in males. These images are from mice.

31. In the next slide, we see how Sry appears to be involved with migration of mesonephric cells into the gonad: • Notice in experiment A that it appears that the urogenital rudiment is the key feature that is going to be activated by the Sry gene and NOT the mesonephros. • Also notice in A how the –Sry urogenital rudiment is not associated with mesonephric cell migration • In B, the apparent factor from Sry in this process is the Fgf9 (fibroblast growth factor 9).

32. Migration of mesonephric endothelial cells into Sry+ gonadal rudiments

33. Phenotypic sex reversal in humans having two copies of the DAX1 locus The DAX1 locus is capable of reversing chromosomal sex of a male fetus if it occurs as an inserted/replicated mutation where there are two copies present on the males X chromosome.

34. Gonadal dysgenesis– a grouping applied to several congenital developmental disorders of the reproductive system. • Typically, there is developmentally a progressive loss of germ cells on the developing gonads of the embryo. • This loss leads to extremely hypoplastic (underdeveloped) and dysfunctioning gonads mainly composed of fibrous tissue. • The accompanying hormonal failure prevents the development of secondary sex characteristics in either sex, resulting in a sexually immature female phenotype and infertility whether genetically male or female. • Swyer syndrome, or XY gonadal dysgenesis, is most common in males • “Pure” Gonadal Dysgenesis” (PGD) is the most common form in XX females.

35. Wnt – represents a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell. Embryonic processes Wnt controls are varied and we have seen some previously, including body axis patterning, cell fate specification, cell proliferation, and cell migration. Wnt is very important in guiding the structural development of the accessory structures of the genitalia.

36. Model for the formation of external genitalia In the flow diagram below, the dark red indicates high activity. The lighter colors indicate progressively lower activity: Males  androgens suppress Wnt inhibitors, leading to Wnt activity and development of male genitalia. Females  the lack of androgens (or very low androgens) is unable to suppress Wnt inhinitors, leading to minimal to no Wnt activity, and estrogens will promote female genitalia development

37. Androgen insensitivity syndrome • Androgen Insensitivity Syndrome (AIS) - a condition that results in the partial or complete inability of cells of the body to respond to androgens. • impair (usually prevents) the masculinization of male genitalia in the developing fetus • suppresses the development of male secondary sexual characteristics at puberty

38. Testosterone- and dihydrotestosterone-dependent regions of the human male genital system

39. Gynandromorph finch with ZZ (male) cells on its right side and ZW (female) cells on its left side A gynadomorph is an organism that contains both male and female characteristics. True hermaphrodites would be considered gynadomorphs. The cause of this condition is typically an event in mitosis in very early development. Where one of the dividing cells does not split its sex chromosomes typically. This leads to one of the two cells having sex chromosomes that cause male development and the other cell having chromosomes that cause female development. (For example, an XY cell undergoing mitosis duplicates its chromosomes, becoming XXYY. Usually this cell would divide into two XY cells, but XX and YY could also occur).

40. Organization of brain development by hormones The aromatase enzyme is able to convert testosterone into estradiol (androgens into estrogens). ATD = androstatriendione is an estrogen inhibitor AFP = alpha-feotoprotein gene that produces alpha-fetoprotein. This protein is produced in the brain to convert testosterone into estrogen for MALE brain development.

43. Masculinization of the brain by hormones (Part 1)

44. Masculinization of the brain by hormones (Part 2)

45. Gynandromorph insects A gynadomorph insect has both male and female characteristics.

46. Proposed regulatory cascade for Drosophila somatic sex determination

47. Proposed regulatory cascade for Drosophila somatic sex determination (Part 1)

48. Proposed regulatory cascade for Drosophila somatic sex determination (Part 2)

49. Demasculinization of frogs by low amounts of atrazine

50. Possible chain of causation leading to the feminization of male frogs and the decline of frog populations in regions where atrazine has been used to control weed populations