Practice Problems Quiz 6 Flashcards
- Klinefelter’s syndrome is a relatively rare genetic disorder characterized by 47XXY karyotype. Individuals typically develop as males, with low fertility and a specific phenotype (see image). Consider the following case report: “During the third pregnancy of R.M., who had previously given birth to a normal son and daughter, a routine prenatal diagnosis was performed at 16 wk of gestation because of her advanced maternal age of 331⁄2 yr. A 47,XXY karyotype diagnostic for Klinefelter syndrome was found in all of the 16 investigated fetal amniocytes derived from two independent cell-culture flasks. At birth, however, the newborn presented with a female, not male, phenotype, with normal female external genitalia, and with bilateral clubbed feet. Karyotype analysis from peripheral blood lymphocytes of the newborn girl, B.M., con- firmed the cytogenetic result obtained during pregnancy: 47,XXY, with no indication of mosaicism (15 metaphases analyzed). Additionally, the karyotypes of both parents were investigated. In the father, a normal 46,XY male karyotype was found, whereas cytogenetic analysis of 13 metaphases from peripheral lymphocytes of the mother, R.M., unexpectedly revealed the same 47,XXY karyotype as her daughter B.M. Again, no evidence for mosaicism was found, and the sex chromosomes and autosomes were of apparently normal structure.” Discuss ways in which a 47XXY individual could have a fertile female phenotype, and speculate whether these individuals are likely to have any male phenotypic elements (prostate, testes, etc.).
http://www.ncbi.nlm.nih.gov/pubmed/11173857. The report states “The mother carries a structurally altered Y chromosome [in which] Yp material, including SRY, has been replaced by terminal Xp sequences. The fertility of the XXY mother can be attributed to the presence of the additional X chromosome that is missing in XY gonadal dysgenesis females. To our knowledge, this is the first human XXY female described who is fertile.” In this situation, it is unlikely that any male phenotypic components persist, since the gonads developed as female, and therefore did not produce testosterone.
- National Organization for Rare Disorders (NORD) includes a listing for a Wnt4-related condition, described below : “…a rare genetic disorder that affects females. It is characterized by the absence or underdevelopment of the uterus and sometimes absence or underdevelopment of the vagina. Affected females also experience abnormally high levels of androgens (hyperandrogenism), which are male sex hormones. Androgens promote and control the development of male sex characteristics and, consequently, affected females may have certain symptoms such as a male pattern of hair growth (hirsutism). Females with WNT4 develop normal secondary sexual characteristics during puberty (e.g., breast development and pubic hair), but do not have a menstrual cycle (primary amenorrhea). The failure to begin the menstrual cycle may be the initial clinical sign of this disorder. This disorder can cause significant psychological challenges and counseling is recommended. In some cases, affected individuals may have kidney (renal) abnormalities such as absence of one kidney (unilateral kidney agenesis). This condition may cause affected individuals to have an increased susceptibility to urinary tract infections and/or kidney stones (renal calculi).” Discuss 1) why this disorder is only seen in females, 2) what the likely source of high levels of androgens might be and 3) whether the condition is likely to be due to a loss of function of Wnt4, reduced function, or misexpression of the Wnt4 gene
Discussion: Wnt4 plays important roles in formation of the gonads, kidneys, lungs and other structures. SERKAL syndrome (female sex reversal and dysgenesis of kidneys, adrenals, and lungs) is a lethal human syndrome associated with complete loss (or severe deficiency) of Wnt4: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2253972/ In this condition, 46XX individuals develop as phenotypic males, but typically die due to the other abnormalities listed. In contrast, the condition described by NORD is likely to be due to incomplete loss of Wnt4 function, resulting in the gonads developing at least partially along a male pattern and producing low levels of testosterone. Interestingly, this condition is likely to occur in both males and females, but due to relatively normal male development in XY patients with reduced Wnt4, male patients are likely to be diagnosed as having a kidney disorder of unknown etiology, with the association with Wnt4 function being undetected.
- Cases of 5-alpha-reductase deficiency have been intensively studied for decades to investigate the contributions of testosterone exposure and societal gender roles in gender identity at puberty. Most studies confirm that in cases where the testes were not removed (i.e. testosterone exposure was normal in prenatal and postnatal life), most patients undergo a shift from a female to a male gender identity at puberty (see for example: http://www.ncbi.nlm.nih.gov/pubmed/431680). In cases where the testes were removed at birth due to genital ambiguity, and patients were raised female, results are much more variable (see, for example, this study reporting 60% of patients raised as female elect to switch gender to male; http://www.ncbi.nlm.nih.gov/pubmed/23044880). Review the roles of testosterone and dihydrotestosterone in male reproductive development and discuss the factors that should be considered in management of 46XY infants presenting with 5-alpha-reductase deficiency.
Discussion: 5-α reductase deficiency causes an intersex condition (pseudovaginal perineoscrotal hypospadias). It was first discovered in indigenous cultures of Papua, New Guinea, where children were born with feminine genitalia in the absence of endogenous DHT during pregnancy, but with the surge of testosterone during adolescence, changed to males at puberty. Because of this change at puberty, the condition is also sometimes called “guevedoche.” There is a range of external appearance that has been described of external genitalia at birth, with varying degrees of virilization. Currently, individuals with ambiguous genitalia at birth are routinely tested for DHT deficiency. Factors contributing to management are complex, and include the extent of the genital anomaly, likely functional state of the gonads and other reproductive anatomy and (most controversially) the will of the parents. In addition, early surgical management tends to have better outcomes, but is undertaken without the informed consent of the patent.
A pathologist has received a biopsy or uterus taken from late in the menstrual cycle, several days before menstrual bleeding begins in the next cycle. Fortunately for the patient, the biopsy is totally normal. What is the histological appearance of the uterus in this sample? Myometrium is thick; endometrium consists of a thin lamina basalis and virtually no lamina functionalis Myometrium is thick; endometrium consists of a thin lamina basalis and thick lamina functionalis with narrow, straight tubular glands Correct Answer Myometrium is thick; endometrium consists of a thin lamina basalis and thick lamina functionalis with distended, coiled sacculated glands Myometrium is thin; endometrium consists of a thin lamina basalis and virtually no lamina functionalis Myometrium is thin; endometrium consists of a thin lamina basalis and thick lamina functionalis with narrow, straight tubular glands Myometrium is thin; endometrium consists of a thin lamina basalis and thick lamina functionalis with distended, coiled sacculated glands
Myometrium is thick; endometrium consists of a thin lamina basalis and thick lamina functionalis with distended, coiled sacculated glands: The biopsy was taken during the secretory phase of the menstrual cycle. During this phase, the functionalis is much thicker and the tubular glands are coiled and full of secretory product.
A
The biopsy was taken during the menstrual phase of the menstrual cycle. At the end of this phase, much of the functionalis layer of the endometrium has been sloughed off.
The primary spermatocyte is one of the most frequently seen cells of the seminiferous
tubule epithelium. Which of the following is the best explanation for the prevalence of this cell type?
The primary spermatocytes are in an extended stage of meiosis.
The primary spermatocytes are most intimately associated with the Sertoli cells and thereby receive increased metabolic support.
The primary spermatocytes divide very rapidly and are thus more numerous.
The mitotic division of spermatogonia provides a constant source of primary spermatocytes.
The primary spermatocytes are the largest cells of the tubules
The primary spermatocytes are in an extended stage of meiosis.
These cells remain in meiosis I for approximately 3 weeks.
The initiation of the secretory phase of the uterus coincides with the:
Recruitment of primordial follicles
Establishment of the zona pellucida
Establishment of the corpus luteum
Peak of LH secretion
Constriction of the coiled (spiral) arteries
Establishment of the corpus luteum
Once ovulation has occurred the corpus luteum forms and becomes a temporary endocrine organ secreting progesterone. The progesterone stimulates the epithelial cells of the uterine glands to become coiled, and secret and accumulate glycogen.
Which of the following hormones causes secretion of glycogen by epithelium of the female reproductive tract?
LH
Estrogen
FSH
Progesterone
Progesterone
Progesterone secreted from the corpus luteum stimulates the epithelial cells of the uterine glands to become coiled and secret and accumulate glycogen.
The blood-testis barrier is formed by:
Tight junctions between endothelial cells in testicular capillaries
Tight junctions between spermatogonial cells
Tight junctions between Sertoli cells
Gap junctions between developing spermatocytes
Extracellular matrix laid down by Leydig cells
Tight junctions between Sertoli cells
This barrier is the tightest blood-tissue barrier in mammals and is part of a system to prevent autoimmune attacks against spermatogenic cells, which are formed after the immune system is mature.
The mature follicle is converted into the corpus luteum:
When the zona pellucida is formed
When human chorionic gonadotropin is present in the blood
When the basement membrane is penetrated by blood vessels
When the basement membrane is penetrated by blood vessels
After ovulation, the granulose and thecal layers collapse and fold in, the capillaries are disrupted and invade the granulose layer.
Sloughing of the lamina functionalis of the endometrium is the direct result of:
Increased blood levels of estrogen
Constriction of the spiral (coiled) arteries
Decreased blood levels of FSH
Constriction of the straight arteries
Constriction of the spiral (coiled) arteries
When fertilization does not occur, the drop in progesterone produces spasms of muscle contraction in the spiral (coiled) arteries, interrupting blood flow. This also causes the release of prostaglandins, causing constriction. As a result of hypoxia, cytokines are releases that trigger release of proteins that degrade the basement membranes.
Sperm become mature and mobile in the:
Seminiferous tubules
Epididymis
Seminal vesicle
Ampulla of ductus deferens
Prostate
Epididymis
Fluids within the epididymis contain decapacitation factors that block the acrosome reaction in the sperm until it is within the female reproductive tract. Sperm are not fully mature until they pass through the epididymis.
The monthly ovarian cycle in the human female is characterized by a recruitment of several primordial follicles to return to the meiotic cell cycle. However, only one of these follicles is usually ovulated, the remainder become atretic. What is the most likely explanation for this process?
The dominant follicle secretes progesterone, which inhibits the further development of other follicles
The dominant follicle establishes an increased sensitivity to FSH
The ovarian stroma can provide metabolic support for only one Graafian follicle
Most of the recruited follicles contain oocytes that have accumulated mutations and become unviable
Granulosa cells of the dominant follicle establish tight junctions, which increase metabolite concentration of the antral fluid
The dominant follicle establishes an increased sensitivity to FSH
Although there are likely complex hormonal balances that control selection, it is clear that FSH prompts follicular growth and development. The dominant follicle likely expresses more FSH receptor, which causes it to be more responsive to the effects of FSH.
The proliferative phase of the uterine cycle is primarily maintained by which of the following hormones?
Estrogen
Progesterone
LH
FSH
Estrogen
The proliferative phase is often called the “estrogenic” phase. These estrogens are secreted by the thecal cells of developing follicles. Progesterone, while present, is more important for the secretory phase.
What secretory product is characteristic, or diagnostic, of the prostate gland?
Acid phosphatase
Ascorbic acid
Fructose
Sialoproteins
Testosterone
Acid phosphatase
The prostrate produces acid phosphatase. This marker used to be used to test for prostate cancer and can be used to detect the presence of semen.
The epithelial lining of the uterus is most similar to that of the:
Vagina
Cervix
Vas deferens
Ovary
Oviduct
Oviduct
Both the oviduct and the uterus have simple columnar epithelium with interspersed ciliated cells.
Spermatogonia give rise to primary spermatocytes by what form of cell division?
mitosis
meiosis
mitosis followed by meiosis
no cell division is involved
Mitosis
Spermatogonia first undergo clonal divisions that leave the cells as a syncytium, then undergo a final mitotic division to produce two cells (either spermatogonia or spermatocytes committed to meiosis).
E,F
The oocyte completes its first meiotic division right before ovulation (F).
Leydig cells of the interstitial testicular space are responsible for the production of testosterone. These cells are inactive in adolescent males, and are absent in females. What accounts for the presence of testosterone in prepubescent boys and in females?
Conversion of estrogen to testosterone in the hypothalamus
De novo synthesis of testosterone in responsive tissues
Low level secretion of testosterone by the adrenal cortex
Conversion of corticosteroid to testosterone in responsive tissues
Absorption of ingested testosterone in the duodenum
Aderenal cortex
The adrenal cortex produces low levels of testosterone. At puberty, Leydig cells are stimulated to produce testosterone by LH, which is in turn triggered by GnRH (gonadotropin releasing hormone) from the hypothalamus.
During spermiogenesis, which of the following cells is the first that will contain either an X or Y chromosome, but NOT BOTH, in its prophase nucleus?
Spermatogonial cell
Primary spermatocyte
Secondary spermatocyte
Early spermatid
Motile spermatozoon
Secondary spermatocyte
The secondary spermatocyte has undergone Meiosis I but not Meiosis II. Therefore, it is haploid with 23 chromosomes (22 + X or 22+ Y). Each consists of 2 chromatids so they are still 2N. The primary spermatocyte is diploid, has 44 +XY chromosomes and is 4N.
Smooth muscle contractions involved in sperm ejaculation occur in which organ of the male reproductive system?
Epididymis
Ductus deferens
Seminal vesicle
Prostate gland
Bulbourethral glands
The ductus deferens has a very thick muscularis which when stimulated produce strong peristaltic contractions that move sperm along the duct from the epididymis.
What are the stem cells of the germ cell population of the seminiferous epithelium?
Primary spermatocytes
Secondary spermatocytes
Spermatids
Spermatogonia
Spermatogonia divide by mitosis to produce stem cells, transient amplifying cells and spermatocytes committed to meiosis.
E
F
B
- Ovulation is caused by a spike in LH and FSH release. What causes this spike to occur?
A. Decreased GnRH from the hypothalamus
B. Decreased ovarian estrogen release
C. Decreased ovarian progesterone release
D. Elevated ovarian estrogen release
E. Elevated ovarian progesterone release
D. Elevated ovarian estrogen release
- The corpus luteum prevents a second ovulatory event within one menstrual cycle primarily by secreting:
A. estrogen & progesterone
B. follicle-stimulating hormone and progesterone
C. follicle-stimulating hormone and luteinizing hormone
D. Luteinizing hormone and progesterone
A. estrogen & progesterone
- During the luteal phase of the ovarian cycle a woman’s basal body temperature increases by ~0.4°C. The action of which hormone, that is normally only high during the luteal phase, is most likely responsible for this temperature increase?
A. Estrogen
B. Follicle-stimulating hormone
C. Human chorionic gonadotropin
D. Leptin
E. Luteinizing hormone
F. Oxytocin
G. Progesterone
G. Progesterone
- During the early follicular phase of the ovarian cycle, what is most likely occurring in the uterus?
A. Increase in the number, length and complexity of the spiral arteries
B. Shedding of the functional layer of the endometrium
C. Thickening of the functional layer of the endometrium
D. Transcriptional induction of the progesterone receptor within the endometrium
B. Shedding of the functional layer of the endometrium
- If implantation of a zygote occurs in the endometrium, production of what hormone by the blastocyst prevents the atrophy of the corpus luteum?
A. Chorionic gonadotropin
B. Estrogen
C. Follicle-stimulating hormone
D. Luteinizing hormone
E. Progesterone
A. Chorionic gonadotropin
- One of the key functions of progesterone during pregnancy is to prevent uterine contractions (“quiet the myometrium”). The mechanism of action of progesterone most likely includes:
A. Activating adenylate cyclase to produce increased cAMP and active protein kinase A.
B. Allosterically activating a cell surface tyrosine kinase receptor and promoting a MAP kinase-signaling cascade
C. Binding to a nuclear hormone receptor to directly alter gene expression
C. Binding to a nuclear hormone receptor to directly alter gene expression
- Elevated blood levels of which hormone are most likely to be diagnostic of menopause?
A. Estrogen
B. Follicle-stimulating hormone
C. Human chorionic gonadotropin
D. Leptin
E. Luteinizing hormone
F. Oxytocin
G. Progesterone
B. Follicle-stimulating hormone
A. Obesity
B. Ovarian cancer
C. Polycystic ovarian disease
D. Pregnancy
E. Premature menopause
F. Primary amenorrhea
D. Pregnancy
- Birth control pills function to inhibit follicular development and ovulation. The hormones in the pill reduce the cyclic pulses of gonadotropin-releasing hormone (GnRH) and inhibit the release of the gonadotropins. Therefore, birth control pills most likely contain small amounts of:
A. Estrogen and progesterone
B. Follicle-stimulating hormone
C. Human chorionic gonadotropin
D. Leptin
E. Luteinizing hormone
F. Oxytocin
A. Estrogen and progesterone
- On average, obese girls have earlier menarche than girls of normal body weight. One likely reason is that hypothalamic signaling of an adipose-derived hormone is important in establishing the rhythmic pulses of GnRH. This adipose-derived hormone is most likely:
A. Estrogen
B. Follicle-stimulating hormone
C. Human chorionic gonadotropin
D. Leptin
E. Luteinizing hormone
F. Oxytocin
G. Progesterone
D. Leptin
A. Clitoris, B. Urethra, C. Vagina, D. Anus, E. Bulb of the vestibule, F. Greater vestibular gland, G. Perineal membrane on deep perineal pouch, H. Ischiocavernosus muscle, I. Bulbospongiosus muscle, J. Superficial transverse perineal muscle, K. Levator ani muscle, L. Gluteus maximus muscle