Lippincot's Q&A Embryology

11 A 20-year-old woman is surprised to discover that she is pregnant. Following a review of her menstrual history and sexual activity, her physician determines that she is in the 4th week of pregnancy. Which of the following best describes the condition of the embryo at this time? (A) Gastrulation is complete, resulting in two germ layers (B) The embryo is entering a period of relative resistance to teratogenic substances (C) Neurulation is nearly complete (D) Somites have not yet formed (E) The trophoblast is present, but the syncytiotrophoblast has not yet formed

11 The answer is C: Neurulation is nearly complete. Neurulation (the process of formation of the neural tube) begins late in week 3 with formation of the neural groove and neural folds. However, most of the process, including formation and completion of the neural tube, occurs during week 4. Additional major events during this week include much of somite differentiation, the appearance of the pharyngeal (branchial) apparatus, and the appearance of the upper limb bud. Choice A (Gastrulation is complete, resulting in two germ layers) is incorrect. Gastrulation is the process of formation of the trilaminar germ disc, that is, establishing the three germ layers: ectoderm, endoderm, and mesoderm. Gastrulation is the defi ning characteristic of week 3 of development. Remember "threes": three germ layers in week 3. Choice B (The embryo is entering a period of relative resistance to teratogenic substances) is incorrect. Weeks 3 to 8 constitute the embryonic period of development, which is the period of organogenesis during which the three germ layers form all tissues and organs. By the end of week 8, the main organ systems are formed and the major external body features are established. This is also regarded as the sensitive period of development because the organ primordia are very sensitive to teratogenic agents. As a result, most gross structural organ defects are induced during this time. Choice D (Somites have not yet formed) is incorrect. Somite formation is normally well underway during the 4th week. Segmentation of the paraxial mesoderm into somitomeres and somites begins late in week 3, with 4 to 7 pairs of somites formed at the cranial end of the embryo at day 21. New somites are added in a craniocaudal sequence at a rate of about 3 pairs per day. There are typically 26 to 29 pairs by the end of week 4, increasing to 42 to 44 pairs at the end of week 5. Because somites appear at a very specifi c rate, their number can be used to determine the age of the embryo with great accuracy during weeks 3 to 5. Choice E (The trophoblast is present, but the syncytiotrophoblast has not yet formed) is incorrect. Differentiation of the trophoblast (the outer cell mass of the blastocyst) into cytotrophoblast and syncytiotrophoblast areas occurs early in week 2. These layers form the fetal component of the placenta and thus are critical to full implantation. At the same time, the embryoblast (the inner cell mass of the blastocyst) differentiates into the bilaminar germ disc, consisting of the epiblast and hypoblast.

3 A 43-year-old pregnant woman at 16 weeks of gestation comes to her OB/GYN for a normal examination. During routine blood tests, her serum a-fetoprotein (AFP) concentration is markedly decreased for her gestational age. Which abnormality or condition will the physician need to rule out based upon these low AFP levels? (A) Down syndrome (B) Spina bifi da (C) Anencephaly (D) Multifetal pregnancy (E) Hepatocellular carcinoma

3 The answer is A: Down syndrome. In the serum AFP test, sometimes called the maternal serum AFP (MSAFP), a blood sample is drawn from the mother to check the levels of AFP. This blood test is most accurate when the initial sample is obtained between 16 and 18 weeks of gestation. AFP is a protein secreted by the fetal liver and fetal yolk sac and absorbed into the mother's blood. Decreased levels of MSAFP are associated with chromosomal defects, including Down syndrome (trisomy 21) and trisomy 18, which will need to be ruled out in this patient with additional tests, such as amniocentesis for chromosomal analysis. See the given fi gure of a karyotype of Down syndrome (trisomy 21), and note the encircled abnormality at chromosome 21. Pregnant women over the age of 35 have an increased incidence of having children with chromosomal abnormalities. Elevated levels of MSAFP are generally associated with neural tube defects. However, raised levels may also indicate other anomalies, including abdominal wall defects, esophageal and duodenal atresia, some renal and urinary tract anomalies, Turner syndrome, some low-birth-weight fetuses, placental complications, and a multifetal pregnancy. Choice B (Spina bifi da) is incorrect. Spina bifi da is a developmental defect involving incomplete closure of the embryonic neural tube, resulting in an incompletely formed spinal cord. In addition, the vertebrae overlying the open portion of the spinal cord do not fully form and remain unfused and open. This neural tube defect would lead to an elevated level of MSAFP, so it can be ruled out. Choice C (Anencephaly) is incorrect. Anencephaly is one of the most severe, typically fatal forms of a neural tube defect. Anencephaly is an incomplete closure of the cranial neural tube (i.e., the brain), accompanied by incomplete formation of the skull. This neural tube defect would lead to elevated MSAFP, so it can be ruled out. Choice D (Multifetal pregnancy) is incorrect. If the mother were carrying twins or triplets, the MSAFP would be elevated, which is not seen in this patient. Choice E (Hepatocellular carcinoma) is incorrect. Malignant hepatic cells produce the glycoprotein AFP. This patient has no history of liver problems, and the diagnosis of hepatocellular carcinoma is not valid because it would lead to elevated AFP levels.

4 A 32-year-old pregnant woman at 30 weeks of gestation comes to her physician due to excess weight gain in a 2-week period. Ultrasonography reveals polyhydramnios. Which fetal abnormality is most likely responsible for the polyhydramnios? (A) Bilateral kidney agenesis (B) Urinary tract obstruction (C) Uteroplacental insuffi ciency (D) Hypoplastic lungs (E) Esophageal atresia

4 The answer is E: Esophageal atresia. Polyhydramnios is associated with the inability of the fetus to swallow because of esophageal atresia or anencephaly. Polyhydramnios can also be due to absorption defects such as duodenal atresia. The inability of the embryo to swallow amniotic fl uid means that the fl uid will not be absorbed into the fetal blood, removed by the placenta, and passed into the maternal blood. Therefore, the amount of fl uid in the amniotic cavity is greater than normal causing polyhydramnios. Choice A (Bilateral kidney agenesis) is incorrect. Bilateral kidney agenesis would lead to reduced amniotic fl uid volume (oligohydramnios) because the fetal kidneys, when present, increase the amniotic fl uid volume through fetal urine production. Choice B (Urinary tract obstruction) is incorrect. Fetal urinary tract obstruction is defi ned as partial or complete obstruction of any portion of the urinary tract from the kidney to the urethra. This obstruction would not allow the fetal urine to enter the amniotic cavity, so this condition would lead to decreased amniotic fl uid volume (oligohydramnios). Choice C (Uteroplacental insuffi ciency) is incorrect. Uteroplacental insuffi ciency is defi ned as insuffi cient blood fl ow to the placenta during pregnancy. This condition can negatively affect the fetus, leading to "fetal distress." However, uteroplacental insuffi ciency leads to oligohydramnios, which is not seen in this patient. Choice D (Hypoplastic lungs) is incorrect. Hypoplastic lungs are often caused by inadequate amounts of amniotic fl uid (oligohydramnios). Swallowing of the amniotic fl uid by the fetus promotes normal lung development, so hypoplastic lungs are associated with oligohydramnios, not polyhydramnios.

1 A young couple hoping for a pregnancy buys an overthe- counter pregnancy kit. What substance will this test most likely detect? (A) Early pregnancy factor (EPF) (B) Human chorionic gonadotropin (C) Progesterone (D) Estrogen (E) Luteinizing hormone (LH)

1 The answer is B: Human chorionic gonadotropin. Early pregnancy detection kits most likely detect the level of human chorionic gonadotropin (hCG) in the female. hCG is a glycoprotein hormone produced by the syncytiotrophoblast to prevent the disintegration of the corpus luteum of the ovary. While hCG is a reliable marker of pregnancy, it cannot be detected until after implantation (6 to 12 days after fertilization), which results in false negatives if the test is performed during the very early stages of pregnancy. Choice A (Early pregnancy factor [EPF]) is incorrect. EPF is a protein believed to be the earliest possible marker of pregnancy. It is present in the maternal serum (blood plasma) shortly (24 to 48 hours) after fertilization. Though current methods for detecting EPF are highly accurate, this pregnancy test is costly. Therefore, modern over-the-counter pregnancy tests detect hCG, especially due to its presence in the urine of the pregnant woman. Choice C (Progesterone) is incorrect. Progesterone is a steroid hormone produced by the ovaries, brain, and placenta of pregnant females. In the menstrual cycle, progesterone production remains low until after ovulation. Then, the corpus luteum (the remnant of the collapsed ovarian follicle after ovulation) produces progesterone, which builds the lining of the uterus for implantation of the fertilized oocyte (preimplantation embryo). Though important for successful pregnancy, progesterone is not used to detect a pregnancy. Choice D (Estrogen) is incorrect. Estrogen is a steroid hormone produced by the developing follicles in the ovary, the corpus luteum, and the placenta. This hormone promotes the development of female secondary sex characteristics and is involved in the thickening of the endometrium. Though important for a normal menstrual cycle, estrogen is not used to detect a pregnancy. Choice E (Luteinizing hormone [LH]) is incorrect. LH is a glycoprotein that experiences an acute rise before ovulation in the menstrual cycle. Though important for the menstrual cycle, LH is not used to detect a pregnancy.

10 A 28-year-old woman who does not know that she is pregnant undergoes a chemotherapy treatment at the end of her 1st week of pregnancy. Chemotherapy is associated with slowing the rate of mitosis in exposed cells, which is good in cancer treatment. However, this treatment may also have a negative infl uence on the implantation and growth of an embryo. In which of the following layers would a lowered rate of cell division be most likely to hinder implantation of the blastocyst? (A) Amnioblast (B) Epiblast (C) Hypoblast (D) Cytotrophoblast (E) Syncytiotrophoblast

10 The answer is D: Cytotrophoblast. The trophoblast forms the fetal part of the placenta, so it is concerned with implantation. The cytotrophoblast is the mitotically active inner part of the trophoblast, and it forms the primary chorionic villi that extend into the syncytiotrophoblast. The cytotrophoblast also provides the cells that migrate into the syncytiotrophoblast and allow it to expand. Thus, chemotherapy may directly affect mitotic activity in the cytotrophoblast, causing stunted growth of both it and the syncytiotrophoblast and possibly hindering implantation. Choice A (Amnioblast) is incorrect. Amnioblasts are the epiblast cells that line the amniotic cavity adjacent to the cytotrophoblast. They are mitotically active in the growth of the amniotic membrane; however, they are not involved in implantation. Choice B (Epiblast) is incorrect. The epiblast is the dorsal cell layer of the bilaminar germ disc. It contributes to the formation of the embryo proper. While certainly mitotically active, it is not involved in implantation. Choice C (Hypoblast) is incorrect. The hypoblast is the ventral cell layer of the bilaminar germ disc. It also contributes to the formation of the embryo proper. Choice E (Syncytiotrophoblast) is incorrect. The syncytiotrophoblast is the outer, multinucleated part of the trophoblast that is mitotically inactive. The syncytiotrophoblast erodes the maternal endometrium and contributes to the formation of the primitive uteroplacental circulation. However, its growth depends on incorporation of new cells from the active cytotrophoblast. Thus, chemotherapy in this case would not affect cell division within the syncytiotrophoblast.

12 A 4-month-old male infant presents with a "growing sore" located posterior to his left ear. This sore is diagnosed as a postauricular hemangioma, as seen in the given photo with the auricle pulled anterior. The cells forming the hemangioma are derived from which of the following cell layers? (A) Endoderm (B) Neural crest (C) Neuroectoderm (D) Ectoderm (E) Mesoderm

12 The answer is E: Mesoderm. A hemangioma is a vascular tumor in which an abnormal proliferation of blood vessels leads to a mass resembling a neoplasm. Hemangiomas are mesodermal in origin, as they are formed by embryonic blood cells and the vascular endothelium formed by angioblasts, and may be present at birth. The mesoderm forms during gastrulation when invaginating epiblast cells form an additional germ layer between the endoderm and the ectoderm. The mesoderm has many notable derivatives, including muscle, connective tissue, bone, cartilage, blood cells, dermis of the skin, and organs, such as the kidney, spleen, and gonads. Choice A (Endoderm) is incorrect. Though the endoderm is not responsible for mesodermally derived hemangiomas, it does have many notable derivatives, including hepatocytes, acinar and islet cells of the pancreas, principal and oxyphil cells of the parathyroid gland, epithelial reticular cells of the thymus, and the epithelial lining of the gastrointestinal tract, trachea, bronchi, lungs, urinary bladder, and the female urethra (as well as most of the male urethra). Choice B (Neural crest) is incorrect. Though the neural crest is not responsible for mesodermally derived hemangiomas, it does have many notable derivatives, including the dentin of teeth, Schwann cells, ganglia, pia mater, arachnoid mater, chromaffi n cells of the adrenal medulla, parafollicular (C) cells of the thyroid gland, melanocytes, and pharyngeal arch skeletal components. Choice C (Neuroectoderm) is incorrect. Though the neuroectoderm is not responsible for mesodermally derived hemangiomas, it does have many notable derivatives, including all the neurons within the central nervous system, neurohypophysis, pineal gland, astrocytes, oligodendrocytes, and the retina. Choice D (Ectoderm) is incorrect. Though the ectoderm is not responsible for mesodermally derived hemangiomas, it does have many notable derivatives, including the epidermis, hair, nails, sweat and sebaceous glands, lens of the eye, adenohypophysis, enamel of the teeth, and the olfactory placodes.

13 The notochord forms the initial axial skeletal element of the body and induces the formation of the neural plate. Which of the following structures is the sole postnatal remnant of the embryonic notochord? (A) Spinal cord (B) Nucleus pulposus (C) Rib cage (D) Anulus fi brosus (E) Spinal meninges

13 The answer is B: Nucleus pulposus. The notochord ("back string") is a solid fi brocellular cord that underlies the midline of the neural plate, induces the formation of the neural groove, and forms the template about which the axial skeleton develops. It is almost entirely replaced by sclerotomal cells that condense under the neural tube to form the bodies of the vertebrae. The only remnant of the notochord is the central core portion of each of the intervertebral discs, the nucleus pulposus. This hydrostatic structure is the component of the disc that herniates out of its normal position in cases of herniated ("slipped") discs. Choice A (Spinal cord) is incorrect. The spinal cord is the elongated caudal portion of the neural tube. The notochord lies ventral to the midline of the neural plate and induces formation of the neural groove, thus triggering formation of the neural tube. Choice C (Rib cage) is incorrect. The ribs develop from lateral processes of the primordial vertebrae. The paraxial mesoderm gives rise to somites, which give rise to sclerotomes. The sclerotomes condense around the neural tube and form the vertebral column. Each incipient vertebra gives rise to a pair of costal processes, which form ribs in the thoracic region. The costal processes also contribute to the formation of the transverse processes in the other vertebral regions. Choice D (Anulus fi brosus) is incorrect. The intervertebral discs are composed of two parts: the central nucleus pulposus and the peripheral anulus fi brosus. The anulus part of each disc is formed from the sclerotomal mesenchyme that also forms the vertebrae. It is the fi brocartilage structure that binds the vertebral bodies and stabilizes the position of the nucleus pulposus. Choice E (Spinal meninges) is incorrect. The entire neural tube is surrounded by three layers of membranes, the meninges. The outermost membrane, the dura mater, is derived from the mesoderm. The inner two membranes, the arachnoid and pia mater, are derived from the neural crest.

14 A 22-year-old pregnant woman at 20 weeks of gestation comes to her OB/GYN for a scheduled prenatal examination. Routine blood tests indicate that her serum a-fetoprotein (AFP) concentration is markedly increased for her gestational age. Ultrasonography reveals a lower lumbar spina bifi da in the fetus. During which weeks of gestation did this defect most likely occur? (A) 1 to 2 weeks (B) 4 to 6 weeks (C) 9 to 11 weeks (D) 12 to 15 weeks (E) 16 to 19 weeks

14 The answer is B: 4 to 6 weeks. Neurulation begins late in week 3. The posterior neuropore closes during week 4 (day 27). Failure of the posterior neuropore to close results in lower neural tube defects such as spina bifi da. Choice A (1 to 2 weeks) is incorrect. The anterior neuropore closes at approximately day 25 of the 4th week, and the posterior neuropore also closes during week 4 (at ~day 27). Because neurulation has not yet begun during week 1 or 2, this period of development is not involved in the malformation leading to spina bifi da. Choice C (9 to 11 weeks) is incorrect. Neurulation is complete as the posterior neuropore closes at ~day 27 of week 4 of development. So, weeks 9 to 11 of development are later than the time when a spina bifi da occurs. Choice D (12 to 15 weeks) is incorrect. Neurulation is complete as the posterior neuropore closes at ~day 27 of week 4 of development. So, weeks 12 to 15 of development are later than the time when a spina bifi da occurs. Choice E (16 to 19 weeks) is incorrect. Neurulation is complete as the posterior neuropore closes at ~day 27 of week 4 of development. So, weeks 16 to 19 of development are later than the time when a spina bifi da occurs.

15 A male infant presents with prune belly syndrome, as shown in the given photo. In this syndrome, the abdominal wall musculature is poorly developed, resulting in an abdominal wall so thin that the internal organs are visible and easily palpable. The muscles affected in this condition develop from which of the following embryonic sites? (A) Surface ectoderm (B) Intermediate mesoderm (C) Splanchnic mesoderm (D) Epimere (E) Hypomere

15 The answer is E: Hypomere. Skeletal muscles are derived from the paraxial mesoderm. Most of the paraxial mesoderm segregates into somites, which in turn give rise to myotome, dermatome, and sclerotome units. The myotome is the muscle-producing component. Each myotome splits into two segments: a more posterior epimere and a more anterior hypomere. The hypomere gives rise to the muscles in the anterolateral body wall (including the abdominal wall) and the limbs, whereas the epimere forms the intrinsic muscles of the back. The hypomere (and its derived muscles) is innervated by anterior (ventral) primary rami of spinal nerves. The epimere (and its derivatives) is supplied by posterior (dorsal) primary rami of spinal nerves. Choice A (Surface ectoderm) is incorrect. The ectoderm does not produce skeletal muscles. However, it does form a few small smooth muscles, for example, the dilator and sphincter muscles in the pupil of the eye. In general, the ectoderm forms the outer surface of the body and structures that form as invaginations from the surface, for example, the epidermis (including the hair and nails), subcutaneous glands (including the mammary glands), and the neural tube. Choice B (Intermediate mesoderm) is incorrect. Most of the urinary and genital systems develop from the intermediate mesoderm. This small zone connects the paraxial and lateral plate mesodermal areas. It gives rise to the excretory parts of the urinary system, the gonads, and much of the genital duct work. Choice C (Splanchnic mesoderm) is incorrect. The splanchnic mesoderm is the visceral layer of the lateral plate mesoderm. It becomes closely invested with the endoderm and gives rise to cardiac muscle that forms the myocardium and to the smooth muscle in the wall of the gut tube and its derivatives. Choice D (Epimere) is incorrect. The epimere is the posterior component of the myotome, which forms the deep (intrinsic) layer of back musculature. These muscles are supplied by posterior (dorsal) primary rami of spinal nerves. The abdominal wall musculature, affected in prune belly syndrome, develops from the hypomere, not the epimere.

16 Which structure is derived from the same embryonic primordium as the kidney? (A) Gonad (B) Epidermis (C) Pineal gland (D) Liver (E) Adrenal medulla

16 The answer is A: Gonad. Both the kidneys and the gonads are derived from the intermediate mesoderm. This longitudinal dorsal ridge of mesoderm forms the urogenital ridge, which is involved with the formation of the future kidneys and gonads. Choice B (Epidermis) is incorrect. The epidermis is derived from the ectoderm, not the intermediate mesoderm. The ectoderm is also responsible for the formation of hair, nails, sweat and sebaceous glands, the lens of the eye, adenohypophysis, enamel of the teeth, and the olfactory placodes. Choice C (Pineal gland) is incorrect. The pineal gland is derived from the neuroectoderm, not the intermediate mesoderm. The neuroectoderm is also responsible for all the neurons within the central nervous system, neurohypophysis, astrocytes, oligodendrocytes, and the retina. Choice D (Liver) is incorrect. The liver is derived from the lateral plate mesoderm (specifi - cally the splanchnic mesoderm), not the intermediate mesoderm. The lateral plate mesoderm is a thin plate of mesoderm in which large spaces (intraembryonic coelom) form. These spaces coalesce and divide the lateral plate mesoderm into the intraembryonic somatic mesoderm and the intraembryonic splanchnic (visceral) mesoderm. From the latter, the endocardium and myocardium of the heart, blood cells, endothelium of blood vessels, and the liver develop. Choice E (Adrenal medulla) is incorrect. The adrenal medulla is derived from the neural crest, not the intermediate mesoderm. The neural crest is also responsible for the formation of the dentin of the teeth, Schwann cells, ganglia, pia and arachnoid mater, parafollicular (C) cells of the thyroid gland, melanocytes, and pharyngeal arch skeletal components.

17 A developmental neurobiologist surgically removes the neural crest in the thoracic region of a chicken embryo immediately after closure of the neural tube. Which of the following cell types is most likely to be affected? (A) Cardiac muscle cells (B) Autonomic ganglia in the thoracic cavity (C) Epithelial cells lining the lower respiratory tract (D) Bone cells in the ribs (E) Skeletal muscle cells in the thoracic wall

17 The answer is B: Autonomic ganglia in the thoracic cavity. All autonomic ganglia, plus the dorsal root ganglia, are derived from the neural crest. This tissue originates at the crest of the neural folds as they elevate and fuse to form the neural tube. The crest cells dissociate from the neural folds and migrate into the neighboring mesoderm. Subsequently, they migrate widely to form a diverse assortment of structures throughout the body. Other derivatives include (but are not limited to) Schwann cells, the arachnoid and pia meningeal layers, the skeletal components of the pharyngeal arches and neurocranium, dentin of the teeth, parafollicular (C) cells in the thyroid gland, adrenal medullary (chromaffi n) cells, melanocytes, and cells forming the aorticopulmonary septum in the heart. Choice A (Cardiac muscle cells) is incorrect. Cardiac muscle is derived from the visceral layer of lateral plate mesoderm (splanchnic mesoderm) that surrounds the primitive paired endothelial heart tubes. During cardiogenesis, the heart tubes fuse into a single endocardial tube and the cardiac myoblasts form the thickened myocardium. Choice C (Epithelial cells lining the lower respiratory tract) is incorrect. The epithelium of the lower respiratory tract is formed from the endodermal germ layer. The lower respiratory tract consists of the larynx, trachea, and bronchi. During week 4, the respiratory diverticulum buds off the ventral wall of the primitive gut tube, which is lined with an endodermal epithelium. This diverticulum forms the lower respiratory tract that carries the lining derived from the gut tube. Choice D (Bone cells in the ribs) is incorrect. The ribs are derived from the paraxial mesoderm. The paraxial mesoderm forms somites, which in turn form sclerotome, dermatome, and myotome units. The sclerotomal mesenchyme condenses around the neural tube and forms the vertebral column and anulus fi brosus of the intervertebral discs. The individual vertebrae possess costal elements that expand to form ribs in the thoracic region. Thus, the ribs are also derived from sclerotome. Choice E (Skeletal muscle cells in the thoracic wall) is incorrect. The skeletal muscles in the thoracic wall (e.g., the intercostal muscles) are formed from the paraxial mesoderm via somites. The myotome portion of each somite splits into a more dorsal epimere and a more ventral hypomere. The hypomere gives rise to the muscles in the ventrolateral body wall (including the thoracic wall) and the limbs, whereas the epimere is related to the muscles in the back.

18 A married couple having diffi culty with conception keeps a daily diary of the female's basal body temperature (BBT) throughout the month. On Friday, the woman noted a slight elevation in her BBT of approximately one-half to one degree Fahrenheit (one-quarter to one-half degree Celsius), which may indicate that she is ovulating. If her ovum, depicted on the right side in the given figure, is expelled into the peritoneal cavity from the ovary (ovulation), the secondary oocyte resides at what specifi c stage of meiosis? (A) Prophase of meiosis I (B) Prophase of meiosis II (C) Metaphase of meiosis I (D) Metaphase of meiosis II (E) Meiosis is completed at the time of ovulation

18 The answer is D: Metaphase of meiosis II. The secondary oocyte is arrested in metaphase of meiosis II about 3 hours before ovulation, and it will remain in this meiotic stage until fertilization occurs. Choice A (Prophase of meiosis I) is incorrect. Oogonia are formed in month 5 of a woman's fetal life. Of these 7 million oogonia, 5 million degenerate or become atretic before birth, leaving 2 million oogonia to differentiate into primary oocytes before birth. No oogonia are present at birth. The primary oocytes are dormant in prophase of meiosis I until puberty because they are surrounded by follicular cells, which secrete oocyte maturation inhibitor (OMI) that causes the arrest of meiosis I. Choice B (Prophase of meiosis II) is incorrect. After puberty, 5 to 15 primary oocytes will resume maturation (no longer dormant in prophase of meiosis I) with each ovarian cycle. Usually, only one primary oocyte will reach maturation with each cycle. This primary oocyte will complete meiosis I producing two daughter cells, a secondary oocyte (23 duplicated chromosomes and almost all of the cytoplasm), and the fi rst polar body (23 duplicated chromosomes and almost no cytoplasm). However, this secondary oocyte enters meiosis II and remains arrested in metaphase until (unless) fertilization occurs. Choice C (Metaphase of meiosis I) is incorrect. The ovulated secondary oocyte is arrested in metaphase of meiosis II until fertilization. This secondary oocyte has already completed meiosis I, so it cannot be in the metaphase stage of meiosis I. Choice E (Meiosis is completed at the time of ovulation) is incorrect. The ovulated secondary oocyte is arrested in metaphase of meiosis II until fertilization. Meiosis is only completed if fertilization occurs. If fertilization does not occur, the ovulated secondary oocyte will degenerate approximately 24 hours after ovulation.

19 The amniotic cavity forms during the process of implantation of the blastocyst. The amniotic cavity forms within which of the following structures? (A) Epiblast (B) Hypoblast (C) Cytotrophoblast (D) Syncytiotrophoblast (E) Maternal endometrium

19 The answer is A: Epiblast. The blastocyst typically begins implantation into the uterine wall by day 7. At this time, it consists of an inner cell mass (the embryoblast) and outer cell mass (the trophoblast). Characteristic of week 2, the embryoblast differentiates into the bilaminar germ disc. This consists of two cell layers, a dorsal epiblast and a ventral hypoblast. Splits develop between the epiblast cells and then coalesce and enlarge into a single amniotic cavity. Thus, the amniotic cavity is lined with epiblast cells and is located on the dorsal aspect of the embryo. Remember, the inner cell mass becomes the embryo proper, whereas the outer cell mass becomes the fetal part of the placenta. Choice B (Hypoblast) is incorrect. Hypoblast cells migrate outward to line the inner surface of the cytotrophoblast. Together, they demarcate the exocoelomic cavity (primitive yolk sac). With further development, the primitive yolk sac is reduced in size. Its remnant becomes the secondary yolk sac (defi nitive yolk sac), which will give rise to the gut tube. Choice C (Cytotrophoblast) is incorrect. The outer cell mass (trophoblast) differentiates into two portions: an inner cytotrophoblast and outer syncytiotrophoblast. The cytotrophoblast is mitotically active. It contributes to the wall of the primitive yolk sac, forms the primary chorionic villi that extend into the syncytiotrophoblast, and provides cells that migrate into the syncytiotrophoblast and allow it to expand. Choice D (Syncytiotrophoblast) is incorrect. This is the tissue zone that invades and erodes maternal tissues. It roots into the endometrium to form lacunae fi lled with maternal blood and glandular secretions. This lacunar network forms the primitive uteroplacental circulation. Choice E (Maternal endometrium) is incorrect. This provides the maternal site of implantation. Eroded endometrial blood vessels and glands leak into the lacunar network of the syncytiotrophoblast as part of the early uteroplacental circulation.

2 The given illustration depicts the passage of a human egg through the female reproductive tract from ovulation to implantation. These events occur during the 1st week of development. Fertilization normally occurs at which of the indicated steps?

2 The answer is C: Ampullary region of the uterine tube. Fertilization normally occurs in the ampullary region of the uterine tube, which is the expanded distal end of the uterine tube, located in close proximity to the ovary. Only a minimal percentage (~1%) of sperm deposited in the vagina pass into the uterine cervix. After entering the uterus, sperm travel to the uterine tube and ultimately to its ampulla, which requires several hours. During this time, spermatozoa must undergo both the capacitation and the acrosome reaction to be able to fertilize the oocyte. The fertilized oocyte (zygote) moves through the uterine tube via peristaltic muscular contractions of the tube and ciliary action in the tubal mucosa. The zygote typically reaches the uterine cavity in approximately 3 to 4 days. Choice A (Preovulatory follicle) is incorrect. This labeled step represents the preovulatory follicle stage. At this point, the follicle is large and meiosis II has initiated. The surface of the ovary over the follicle bulges outward and breaks down in preparation for ovulation. Fertilization is not possible at this stage because the oocyte remains protected by the cell layers of the follicle and ovary. Choice B (Immediate postovulation) is incorrect. This labeled step represents the stage at which the oocyte has been released from the ovary (ovulation) and is starting to enter the uterine tube. Before ovulation, the fi mbriae at the distal (free) end of the uterine tube sweep the surface of the ovary, the uterine tube itself begins contracting rhythmically, and cilia on the tubal epithelium activate. These collective actions appear to draw the extruded oocyte into the uterine tube, where the cumulus oophorus cells fall away to better expose the oocyte for fertilization in the ampullary region. Choice D (2-cell stage) is incorrect. In this step, the zygote has achieved the two-cell stage of cleavage, about 30 hours postfertilization. The individual cells (blastomeres) continue to divide as the zygote proceeds down the tube. When it enters the uterine cavity (~3 to 4 days after fertilization), the zygote is typically at the 16-cell stage of division and is termed a morula (L: mulberry). The morula is composed of two parts: (1) the inner cell mass (embryoblast) which will become the embryo proper and (2) the outer cell mass (trophoblast) which contributes to formation of the placenta. Choice E (Early blastocyst stage) is incorrect. At about 4.5 days of development, the labeled zygote is at the early blastocyst stage, and it is located within the uterine cavity. At this stage, the zona pellucida has disappeared, which enables implantation to occur in the uterine mucosa.

20 A married woman who is having diffi culty getting pregnant undergoes an endometrial function test (EFT), which determines that the endometrium of her uterus is not capable of implantation. Which of the following substances would likely increase the chances for implantation of the fertilized oocyte (or preimplantation embryo) into the uterine mucosa? (A) Follicle-stimulating hormone (B) Testosterone (C) Progesterone (D) Estrogen (E) Luteinizing hormone

20 The answer is C: Progesterone. Progesterone is a steroid hormone produced by the ovaries, brain, and placenta of pregnant females. In the menstrual cycle, progesterone production remains low until after ovulation. The corpus luteum (the remnant of the collapsed ovarian follicle after ovulation) produces progesterone, which halts endometrial proliferation and builds the endometrial lining of the uterus in preparation for implantation of the fertilized oocyte (zygote). Therefore, progesterone supplementation would increase the chances for implantation of the fertilized oocyte into the uterine mucosa of this patient. Choice A (Follicle-stimulating hormone) is incorrect. Follicle-stimulating hormone (FSH), a glycoprotein secreted within the anterior pituitary, stimulates the maturation of ovarian follicles. Because increased serum levels of progesterone and estrogen suppress its release, FSH levels remain low during the buildup of the endometrial lining of the uterus, which is crucial for implantation. Also, the production of FSH peaks approximately 3 days after menstruation because serum levels of progesterone and estrogen are low. Therefore, FSH supplementation would decrease the chances for implantation of the fertilized oocyte into the uterine mucosa. Choice B (Testosterone) is incorrect. Testosterone is a steroid hormone secreted by the ovaries and the adrenal gland in females. Approximately 10 to 20 times less testosterone is produced in females compared to males, and it has been used to treat postmenopausal symptoms such as decreased libido. Because testosterone has more of a behavioral effect on females than a physiological one, testosterone supplementation would not increase the chances for implantation of the fertilized oocyte into the uterine mucosa. Choice D (Estrogen) is incorrect. Estrogen is a steroid hormone produced by the developing follicles in the ovary, the corpus luteum, and the placenta. This hormone promotes the development of female secondary sex characteristics and is involved in the thickening of the endometrium by triggering the endometrial cells to divide and proliferate. However, progesterone halts endometrial proliferation and promotes transformation of the endometrium into a receptive platform for implantation to occur. Choice E (Luteinizing hormone) is incorrect. In the menstrual cycle, a surge of luteinizing hormone (LH), a glycoprotein produced by the anterior pituitary, triggers ovulation. It also may play a role in converting the remnants of the collapsed ovarian follicle into the corpus luteum, which ultimately produces the progesterone responsible for building the endometrial lining of the uterus in preparation for implantation. However, the secretion of LH during implantation, which normally occurs 7 days after fertilization, remains at a basal level. Therefore, LH supplementation would not increase the chances for implantation of the fertilized oocyte into the uterine mucosa.

5 Which structure is derived from the same embryonic primordia as the spinal (posterior root) ganglia? (A) Adrenal medulla (B) Kidney (C) Liver (D) Lungs (E) Vertebrae

5 The answer is A: Adrenal medulla. Both the spinal (posterior root) ganglia and the chromaffi n cells of the adrenal medulla are derived from neural crest cells. Other structures derived from neural crest cells include C cells of the thyroid gland, odontoblasts, dermis in the face and neck, sympathetic chain ganglia, Schwann cells, glial cells, and melanocytes. Choice B (Kidney) is incorrect. The kidney is derived from intermediate mesoderm originating from a mesodermal ridge located along the posterior wall of the abdominal cavity. It is not derived from neural crest cells. Choice C (Liver) is incorrect. The liver appears in the middle of the 3rd week as an outgrowth of the endodermal epithelium at the distal end of the foregut. It is not derived from neural crest cells. Choice D (Lungs) is incorrect. The lungs develop from a single outgrowth of the endodermal epithelium from the ventral wall of the foregut. They are not derived from neural crest cells. Choice E (Vertebrae) is incorrect. The vertebrae are derived from paraxial mesoderm, specifi cally the sclerotome portions of the somites. They are not derived from neural crest cells.

6 The given illustration shows a dorsal view of a human embryo. In the embryo, neurulation is well underway, and several distinct somites are present on each side of the neural tube. The development of the embryo depicted in this illustration is typical of which of the following embryonic periods? (A) Week 1 (B) Week 2 (C) Week 3 (D) Week 4 (E) Week 5

6 The answer is D: Week 4. The illustration shows a dorsal view of a human embryo at approximately day 24 (during the 4th week) of development. Week 4 is characterized by most of neurulation, much of somite differentiation, the appearance of the pharyngeal (branchial) apparatus, and the appearance of the upper limb bud. Neurulation (the process of formation of the neural tube) begins late in week 3 with formation of the neural groove and neural folds. However, most of the process, including formation and completion of the neural tube, occurs during week 4. Likewise, segmentation of the paraxial mesoderm into somitomeres and somites begins late in week 3, with 4 to 7 somites formed at day 21. That number increases to 26 to 29 during week 4. Because somites appear at a very specifi c rate, their number can be used to determine the age of the embryo with great accuracy during weeks 3 to 5. This illustration shows nearly complete formation of the neural tube plus 17 defi ned somites, indicating the embryo is well into week 4. The pharyngeal arches and upper limb buds are not seen here, as they fi rst appear later in the 4th week of embryonic development. Choice A (Week 1) is incorrect. Week 1 of embryonic development is characterized by the events of fertilization through implantation. Fertilization occurs in the ampullary part of the uterine tube. The zygote moves through the uterine tube, dividing into the morula (16-cell) stage by the time it enters the uterine cavity. Finally, it forms the blastocyst and begins implantation in the uterine mucosa by day 7. Choice B (Week 2) is incorrect. Week 2 of embryonic development features development of the bilaminar germ disc, which includes the completion of implantation of the embryo into the uterine mucosa and full development of the blastocyst. Remember to think of "twos" for week 2 of development. The blastocyst is composed of two main parts: the inner cell mass (embryoblast) and outer cell mass (trophoblast). The inner cell mass forms the embryo proper and differentiates into two parts that form a bilaminar disc: the epiblast and the hypoblast. The outer cell mass contributes to the formation of the placenta and differentiates into two parts: an inner cytotrophoblast and outer syncytiotrophoblast. Choice C (Week 3) is incorrect. Week 3 of embryonic development is characterized by the formation of the trilaminar germ disc. The featured event within this week of development is gastrulation, which results in formation of all three embryonic germ layers: ectoderm, mesoderm, and endoderm. Thus, we should remember "threes" for week 3. Weeks 3 to 8 are denoted as the embryonic period of development, which is the period of organogenesis during which the three germ layers form all tissues and organs. By the end of the 2nd month, the main organ systems are formed and the major external body features are established. Because organ primordia are very sensitive to teratogenic agents, weeks 3 to 8 of development are regarded as the sensitive period. If exposed to teratogens, gross structural organ defects can manifest during the period of organogenesis. Choice E (Week 5) is incorrect. Week 5 represents approximately the middle of the embryonic period of development, with organogenesis well underway. By the completion of week 5 of development, the embryo has developed signifi cantly beyond the stages of neurulation and somite formation shown in the illustration. Also, the upper and lower limb buds have appeared and the pharyngeal apparatus is differentiating.

A male newborn suffers a complex of congenital defects involving malformation of the urinary and genital ducts. Examination of his family history reveals several members sharing a similar background of urinary and genital problems spanning three generations. These issues may be related to a genetic defect that is expressed in which of the following embryonic sites? (A) Intermediate mesoderm (B) Paraxial mesoderm (C) Neural crest (D) Surface ectoderm (E) Yolk sac endoderm

7 The answer is A: Intermediate mesoderm. The urinary and genital systems both develop from the intermediate mesoderm. The intermediate mesoderm is a small zone that connects the paraxial and lateral plate mesodermal areas and also forms a longitudinal urogenital ridge. This urogenital ridge gives rise to the excretory parts of the urinary system, the gonad, and much of the genital duct work. Thus, defects in genetic signaling and/or teratogenic agents acting on the intermediate mesoderm may express themselves as various defects in the urogenital tracts. Choice B (Paraxial mesoderm) is incorrect. The paraxial mesoderm forms somites. These differentiate into sclerotome, dermatome, and myotome portions. The sclerotome gives rise to the vertebral column, the anulus fi brosus of the intervertebral discs, and the ribs. The dermatome forms the dermis and associated subcutaneous tissues of the skin. The myotomes give rise to the skeletal muscles in the body wall and limbs. Choice C (Neural crest) is incorrect. The neural crest forms a diverse assortment of structures spread widely across the body. This tissue separates off the neural folds and migrates into the neighboring mesoderm and beyond. Derivatives include autonomic ganglia, dorsal root ganglia, Schwann cells, arachnoid and pia meningeal layers, skeletal components of the pharyngeal arches and neurocranium, dentin of the teeth, parafollicular (C) cells in the thyroid gland, adrenal medullary (chromaffi n) cells, melanocytes, and cells forming the aorticopulmonary septum in the heart. Choice D (Surface ectoderm) is incorrect. The ectoderm is the dorsal layer of the trilaminar germ disc. It forms the outer surface of the body and structures that form as invaginations from the surface. Derivatives include the epidermis (including the hair and nails), subcutaneous glands (including the mammary glands), dental enamel, the neural tube, and pituitary gland. Further, the linings of the stomodeum (primitive oral cavity) and proctodeum (primitive anal canal) are derived from surface ectoderm. Choice E (Yolk sac endoderm) is incorrect. The endoderm is the ventral layer of the trilaminar germ disc and forms the lining of the yolk sac. However, in humans, the yolk sac is vestigial, with a minor role in nutrition early in development. Of note, primordial germ cells (that originate in the epiblast) populate the proximal posterior wall of the yolk sac endoderm during week 3. These migrate into the genital ridges and induce the indifferent gonads to develop into either testes or ovaries. The great majority of the endoderm forms the epithelial lining of the gut tube and its derivatives (e.g., lower respiratory tract, urinary bladder and urethra, and middle ear cavity).

8 In a 15-day embryo, the epiblast is capable of forming which of the following germ layers? (A) Ectoderm only (B) Ectoderm and mesoderm only (C) Ectoderm and endoderm only (D) Mesoderm and endoderm only (E) Ectoderm, mesoderm, and endoderm

8 The answer is E: Ectoderm, mesoderm, and endoderm. The epiblast is capable of forming all three germ layers (ectoderm, mesoderm, and endoderm) during gastrulation. Epiblast cells migrate to the primitive streak and invaginate into a space between the epiblast and the hypoblast. The given fi gure shows a cross section through the cranial region of the primitive streak at 15 days, illustrating the invagination of epiblast cells. The invaginating epiblast cells displace the hypoblast to create the defi nitive endoderm. Once the defi nitive endoderm is established, migrating epiblast cells also form the intraembryonic mesoderm. The remaining epiblast cells, which do not migrate through the primitive streak, remain in the epiblast to form the ectoderm. Hence, the epiblast gives rise to all three germ layers in the embryo. Choice A (Ectoderm only) is incorrect. Cells of the epiblast that do not invaginate in the region of the primitive node and streak do remain behind to form the ectoderm. During gastrulation, however, the epiblast forms all three germ layers in the embryo: endoderm, mesoderm, and ectoderm. Choice B (Ectoderm and mesoderm only) is incorrect. The epiblast is capable of forming the ectoderm and mesoderm during gastrulation. However, some of these epiblast cells also displace the hypoblast to form the defi nitive endoderm. Hence, the epiblast gives rise to all three germ layers in the embryo. Choice C (Ectoderm and endoderm only) is incorrect. The epiblast is capable of forming the ectoderm and endoderm during gastrulation. However, migrating epiblast cells also form the intraembryonic mesoderm. Hence, the epiblast gives rise to all three germ layers in the embryo. Choice D (Mesoderm and endoderm only) is incorrect. The epiblast is capable of forming the mesoderm and endoderm during gastrulation. However, the remaining epiblast cells, which do not migrate through the primitive streak, remain in the epiblast to form the ectoderm. Hence, the epiblast gives rise to all three germ layers in the embryo.

9 The given illustration represents a lateral view of an approximately 25-day-old human embryo. Disruption of further development of the structures indicated by the "X" could directly affect the formation of which of the following structures? (A) Bones in the hand (B) Skeletal muscles in the arm (C) Body hair (D) Lining of the intestines (E) Melanocytes in the skin

9 The answer is B: Skeletal muscles in the arm. The structures indicated by the "X" are somites, which ultimately give rise to most of the skeletal muscles of the trunk and limbs, plus numerous other structures. Recall that the mesodermal germ layer segregates into three portions: paraxial, intermediate, and lateral plate. Somites form from the paraxial mesoderm and differentiate into myotome, dermatome, and sclerotome. Each myotome splits into a more dorsal epimere and a more ventral hypomere. The hypomere gives rise to the muscles in the anterolateral body wall and the limbs, whereas the epimere is related to the intrinsic muscles in the back. Thus, disruption of the development of the somites could cause malformations in the development of the muscles in the limbs. The dermatome forms the dermis and associated subcutaneous tissues of the skin. The sclerotome gives rise to the vertebral column, the anulus fi brosus portion of the intervertebral discs, and the ribs. Choice A (Bones in the hand) is incorrect. The bones and connective tissues in the limbs and the dermis in the body wall and limbs are derived from the parietal layer of lateral plate mesoderm. The lateral plate mesoderm splits into parietal (somatic) and visceral (splanchnic) layers related to the lateral body wall folds and incipient gut tube, respectively. The parietal mesoderm and overlying ectoderm form the ventrolateral body wall, including the limb buds. The visceral mesoderm contributes to the wall of the gut tube. Choice C (Body hair) is incorrect. The epidermis, including the hair and nails, is derived from the ectodermal germ layer. The ectoderm also gives rise to subcutaneous glands (such as sweat and sebaceous glands, including the mammary glands), lens of the eye, adenohypophysis, enamel of the teeth, olfactory placodes, and the neural tube. Choice D (Lining of the intestines) is incorrect. The epithelial lining of the gut tube is derived from the endodermal germ layer. However, the outer layers of the wall of the gut tube (including the smooth muscle) are formed mainly from the visceral layer of lateral plate mesoderm. Further, the linings of the stomodeum (primitive oral cavity) and proctodeum (primitive anal canal) are derived from surface ectoderm. Choice E (Melanocytes in the skin) is incorrect. Melanocytes in the skin and hair follicles are derived from the neural crest. This tissue originates at the crest of the neural folds (derived from the ectoderm), dissociates from the neural folds, and migrates into the neighboring mesoderm. Neural crest cells then migrate widely to form a diverse assortment of structures throughout the body.