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Questions and Answers
What is the primary hormone produced by the corpus luteum to maintain the uterine lining?
What is the primary hormone produced by the corpus luteum to maintain the uterine lining?
During which phase of the menstrual cycle does the endometrium first begin to shed?
During which phase of the menstrual cycle does the endometrium first begin to shed?
What occurs to the corpus luteum if pregnancy does not happen?
What occurs to the corpus luteum if pregnancy does not happen?
Which phase of the endometrial cycle is characterized by rising estrogen levels and preparation for implantation?
Which phase of the endometrial cycle is characterized by rising estrogen levels and preparation for implantation?
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What is the approximate duration of the window for implantation after fertilization?
What is the approximate duration of the window for implantation after fertilization?
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What is a recognized symptom of menopause due to hormonal changes?
What is a recognized symptom of menopause due to hormonal changes?
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What is the primary inhibitory effect of the combined oral contraceptive pill (COCP)?
What is the primary inhibitory effect of the combined oral contraceptive pill (COCP)?
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What change occurs to the endometrium during the secretory phase?
What change occurs to the endometrium during the secretory phase?
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What characterizes Polycystic Ovarian Syndrome (PCOS)?
What characterizes Polycystic Ovarian Syndrome (PCOS)?
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What is the role of hCG in early pregnancy?
What is the role of hCG in early pregnancy?
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What are the consequences of excess Reactive Oxygen Species (ROS) on sperm?
What are the consequences of excess Reactive Oxygen Species (ROS) on sperm?
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Which of the following factors are primarily linked to increased sperm DNA fragmentation?
Which of the following factors are primarily linked to increased sperm DNA fragmentation?
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What role does cervical mucus play in sperm transport?
What role does cervical mucus play in sperm transport?
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How does cryopreservation affect sperm functionality?
How does cryopreservation affect sperm functionality?
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During oocyte transport, which structure is responsible for capturing the oocyte after ovulation?
During oocyte transport, which structure is responsible for capturing the oocyte after ovulation?
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Which pathway primarily supports energy demands during the early preimplantation stages?
Which pathway primarily supports energy demands during the early preimplantation stages?
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What is the primary function of Protamine 1 in sperm?
What is the primary function of Protamine 1 in sperm?
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What is the main function of glycine in amino acid metabolism?
What is the main function of glycine in amino acid metabolism?
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At which developmental stage do embryos begin to rely more heavily on glucose metabolism?
At which developmental stage do embryos begin to rely more heavily on glucose metabolism?
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What is the main challenge associated with vitrification compared to traditional cryopreservation?
What is the main challenge associated with vitrification compared to traditional cryopreservation?
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Which statement accurately describes the process of sperm selection during transport?
Which statement accurately describes the process of sperm selection during transport?
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What process occurs first after the sperm binds to the oocyte's plasma membrane?
What process occurs first after the sperm binds to the oocyte's plasma membrane?
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What describes the composition of the morula during early embryonic development?
What describes the composition of the morula during early embryonic development?
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What is a primary role of insulin in metabolic regulation during embryonic development?
What is a primary role of insulin in metabolic regulation during embryonic development?
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Which factor is most critical to embryo viability during developmental stages?
Which factor is most critical to embryo viability during developmental stages?
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What happens to the oocyte immediately after sperm penetration?
What happens to the oocyte immediately after sperm penetration?
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Which metabolic pathway provides the embryo with energy during post-implantation stages?
Which metabolic pathway provides the embryo with energy during post-implantation stages?
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How does the acrosome reaction facilitate fertilization?
How does the acrosome reaction facilitate fertilization?
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Which statement is true about the role of fatty acids in early embryo development?
Which statement is true about the role of fatty acids in early embryo development?
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Which nutrient is predominantly utilized during the early preimplantation stage?
Which nutrient is predominantly utilized during the early preimplantation stage?
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What is the fate of the zygote after the fusion of sperm and oocyte nuclei?
What is the fate of the zygote after the fusion of sperm and oocyte nuclei?
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What role does methylation play in fully differentiated cells?
What role does methylation play in fully differentiated cells?
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What is a consequence of incomplete removal of methylation patterns during iPSC reprogramming?
What is a consequence of incomplete removal of methylation patterns during iPSC reprogramming?
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Which hormone is secreted by the hypothalamus as part of the HPO axis?
Which hormone is secreted by the hypothalamus as part of the HPO axis?
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How do estrogen and progesterone participate in the regulation of the HPO axis?
How do estrogen and progesterone participate in the regulation of the HPO axis?
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What potential impact does selective pressure in stem cell culture have?
What potential impact does selective pressure in stem cell culture have?
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What phase does high estrogen concentration lead to during the menstrual cycle?
What phase does high estrogen concentration lead to during the menstrual cycle?
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Which of the following describes a possible disruption in the HPO axis?
Which of the following describes a possible disruption in the HPO axis?
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What characterizes the initial stages of ovarian follicles before they require FSH?
What characterizes the initial stages of ovarian follicles before they require FSH?
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What happens to granulosa cells as they support a maturing follicle?
What happens to granulosa cells as they support a maturing follicle?
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Which assay method is most essential for confirming the pluripotency of iPSCs?
Which assay method is most essential for confirming the pluripotency of iPSCs?
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In the context of iPSC differentiation, how can altered methylation influence outcomes?
In the context of iPSC differentiation, how can altered methylation influence outcomes?
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What defines the role of the pituitary gland in the HPO axis?
What defines the role of the pituitary gland in the HPO axis?
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What important process occurs during the LH surge related to follicle maturation?
What important process occurs during the LH surge related to follicle maturation?
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What is the primary function of the inner cell mass (ICM) in embryonic development?
What is the primary function of the inner cell mass (ICM) in embryonic development?
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Which hormone is primarily responsible for supporting pregnancy until the placenta takes over?
Which hormone is primarily responsible for supporting pregnancy until the placenta takes over?
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What characterizes the zona pellucida during the blastocyst stage?
What characterizes the zona pellucida during the blastocyst stage?
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What is the effect of progesterone on stromal cells?
What is the effect of progesterone on stromal cells?
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Which condition is characterized by a physical blockage preventing sperm from being present in semen?
Which condition is characterized by a physical blockage preventing sperm from being present in semen?
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What is a common use for Controlled Ovarian Hyperstimulation (COH) in assisted reproduction?
What is a common use for Controlled Ovarian Hyperstimulation (COH) in assisted reproduction?
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What type of stem cell can develop into almost any cell type but not extra-embryonic tissues?
What type of stem cell can develop into almost any cell type but not extra-embryonic tissues?
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Which factor is NOT typically associated with implantation failure?
Which factor is NOT typically associated with implantation failure?
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Which stage does the inner cell mass (ICM) come from in embryonic development?
Which stage does the inner cell mass (ICM) come from in embryonic development?
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What best describes the function of trophoblast cells?
What best describes the function of trophoblast cells?
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What characteristic of stem cells allows them to self-renew?
What characteristic of stem cells allows them to self-renew?
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Which hormone is synthesized by trophoblast cells during early pregnancy?
Which hormone is synthesized by trophoblast cells during early pregnancy?
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What is the significance of the antral follicle count in assessing ovarian reserve?
What is the significance of the antral follicle count in assessing ovarian reserve?
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What is the primary hormone produced by the corpus luteum after ovulation?
What is the primary hormone produced by the corpus luteum after ovulation?
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During which phase of the menstrual cycle does the endometrium thickens due to estrogen?
During which phase of the menstrual cycle does the endometrium thickens due to estrogen?
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What role does progesterone play following ovulation?
What role does progesterone play following ovulation?
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What is the effect of interleukin-1 (IL-1) in the process of embryo implantation?
What is the effect of interleukin-1 (IL-1) in the process of embryo implantation?
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What type of extracellular vesicles (EVs) are involved in maternal-fetal communication?
What type of extracellular vesicles (EVs) are involved in maternal-fetal communication?
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What initiates the blastocyst's attachment and invasion into the endometrium?
What initiates the blastocyst's attachment and invasion into the endometrium?
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What is the main characteristic of the cleavage stage in embryo development?
What is the main characteristic of the cleavage stage in embryo development?
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Which protein is crucial for cell compaction during early embryo development?
Which protein is crucial for cell compaction during early embryo development?
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What is the significance of IGFBP-1 in late secretory phase endometrium?
What is the significance of IGFBP-1 in late secretory phase endometrium?
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Which energy source is primarily used during the pre-compaction stage of embryo development?
Which energy source is primarily used during the pre-compaction stage of embryo development?
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What type of cell forms the placenta during embryonic development?
What type of cell forms the placenta during embryonic development?
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Which type of ion transport is essential for fluid movement into the blastocoele?
Which type of ion transport is essential for fluid movement into the blastocoele?
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What is the primary function of osteopontin in embryonic implantation?
What is the primary function of osteopontin in embryonic implantation?
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What occurs during the hatching phase of the blastocyst?
What occurs during the hatching phase of the blastocyst?
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What role do the glycoproteins ZP3 and ZP4 play in fertilization?
What role do the glycoproteins ZP3 and ZP4 play in fertilization?
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Which hormonal changes occur during the ovarian follicular phase?
Which hormonal changes occur during the ovarian follicular phase?
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What happens immediately following sperm penetration of the zona pellucida?
What happens immediately following sperm penetration of the zona pellucida?
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How does the presence of progesterone affect the implantation process?
How does the presence of progesterone affect the implantation process?
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Which event characterizes the completion of meiosis in the oocyte?
Which event characterizes the completion of meiosis in the oocyte?
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What is a primary function of syncytiotrophoblast cells during implantation?
What is a primary function of syncytiotrophoblast cells during implantation?
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What specific physiological change occurs during sperm capacitation?
What specific physiological change occurs during sperm capacitation?
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Which factors can influence epigenetic profiles throughout life?
Which factors can influence epigenetic profiles throughout life?
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What is the fate of the zygote immediately after fertilization?
What is the fate of the zygote immediately after fertilization?
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Which of the following describes the acrosome reaction?
Which of the following describes the acrosome reaction?
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Which event occurs during the hatching stage of implantation?
Which event occurs during the hatching stage of implantation?
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What role does calcium oscillation play post-fertilization?
What role does calcium oscillation play post-fertilization?
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Which stage immediately follows the sperm-oocyte fusion?
Which stage immediately follows the sperm-oocyte fusion?
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During what phase does luteinizing hormone surge to trigger ovulation?
During what phase does luteinizing hormone surge to trigger ovulation?
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Study Notes
Male Infertility
- 50% of infertility cases involve male factors.
- 40-80% of male infertility cases are linked to Reactive Oxygen Species (ROS).
- ROS are essential for sperm function (capacitation, acrosome reaction), but excess ROS damage sperm (poor motility, abnormal morphology, DNA damage, cell death).
Cervical Mucus Migration Tests
- Mimics the natural female tract.
- High sperm migration correlates with better in vivo fertilization outcomes.
Sperm DNA Fragmentation
- DNA damage reduces fertility; sperm DNA damage cannot be repaired by the sperm, only by the oocyte.
- Increased DNA fragmentation with higher temperatures (37°C).
- Fewer cysteines in Protamine 1 lead to more DNA fragmentation.
- Protamine 1 tightly packs DNA for stability; cysteine bonds ensure DNA protection.
Cryopreservation
- Process involves cooling, freezing, thawing sperm with cryoprotectants like glycerol.
- 50-60% sperm survive freezing, with reduced functionality.
Vitrification
- Rapid cooling method, avoiding ice crystal formation.
- Preserves motility/viability (>50%) even without cryoprotectants.
Key Points to Remember
- Oxidative stress significantly impacts male fertility.
- Lifestyle factors influence DNA fragmentation.
- Cryopreservation and vitrification influence sperm viability.
Sperm Transport
- Sperm deposited in the vagina, >99% lost.
- Sperm enter cervix within minutes; some survive hours in crypts, nourished by mucus.
- Sperm move via uterine contractions to the oviduct (2-7 hours via self-propulsion).
- Uterotubal junction regulates sperm entry into the oviduct.
Sperm Selection & Survival
- Cervical mucus filters sperm, allowing passage during fertile window.
- Morphological abnormal sperm are eliminated in the uterus.
- Sperm form a reservoir on oviducal epithelial cells for gradual release.
- Capacitation occurs in uterus/oviduct, preparing sperm for fertilization.
Oocyte Transport
- Ovulation releases oocyte into peritoneal cavity.
- Fallopian tube fimbriae capture the oocyte.
- Ciliary movement and contractions move oocyte to the ampulla.
- Cumulus cells assist oocyte adhesion and transport.
Fertilization Site
- Ampullary-Isthmic Junction: Sperm and oocyte meet.
- Sperm activation: At ovulation sperm detach; swim to oocyte.
Factors Influencing Transport
- Hormones (estrogen, progesterone) regulate cervical mucus and motility.
- Uterine contractions assist transport but are not essential.
- Chemoattractants potentially guide sperm (e.g., progesterone).
Sperm Capacitation
- Physiological changes after ejaculation enhancing fertilization ability.
- Removal of glycoprotein coats, membrane changes, increase motility, and acrosome reaction potential.
Acrosome Reaction
- Enzymes released from the acrosome digest the zona pellucida for sperm penetration.
Sperm-Oocyte Fusion
- Sperm binds to oocyte plasma membrane.
- Sperm nucleus enters oocyte, forming a zygote.
Cortical Reaction
- Sperm entry triggers cortical granules' release into perivitelline space.
- Modifying zona pellucida prevents polyspermy (multiple sperm).
Completion of Meiosis
- Oocyte completes meiosis II upon fertilization.
- Formed second polar body and mature ovum contribute half genetic material.
Zygote Formation
- Sperm and oocyte nuclei fuse to form diploid zygote.
- Zygote begins cleavage to form multicellular embryo.
Molecular Mechanisms
- Sperm-Zona Pellucida Interaction: Receptors bind to glycoproteins to initiate acrosome reaction.
- Calcium Oscillations: After fertilization, essential for developmental activation and meiosis completion.
Stages of Implantation
- Hatching: Blastocyst escapes zona pellucida, exposing trophoblast.
- Apposition: Initial blastocyst and endometrial surface contact during receptive window.
- Adhesion: Firm attachment via cell surface receptors.
- Invasion: Trophoblast invades endometrium for maternal-fetal connection.
Trophoblast Differentiation
- Cytotrophoblast: Precursor cells, proliferative.
- Syncytiotrophoblast: Invasive, multinucleated cells digest maternal extracellular matrix for deep embedding (using MMPs).
Syncytiotrophoblast Functions
- Anchoring embryo in endometrium.
- Vascular connection for placenta formation and nutrient/oxygen exchange.
- Immune modulation for preventing maternal rejection.
Epigenetic profile
- Set and modified throughout life, critical periods during early development.
- Impacted by factors like environment, medications, and periconception environment.
- Epigenetic reprogramming significantly changes during early development (low methylation to high).
Anterior Pituitary Gland Hormone Regulation
- FSH (Follicle-Stimulating Hormone): Peaks early follicular phase (days 1-7), stimulating follicle recruitment and growth.
- LH (Luteinizing Hormone): Surge (around day 14) triggers ovulation.
Ovarian Hormones
- Estrogen: Produced by developing follicles, rises in the follicular phase, peaks before ovulation; promotes endometrial proliferation.
- Progesterone: Secreted by corpus luteum after ovulation; peaks in luteal phase; stabilizes endometrium for implantation.
Ovarian Events
- Follicular Phase (days 1–14): Follicle recruitment, selection of dominant follicle, ovulation.
- Luteal Phase (days 15–28): Corpus luteum forms, producing progesterone, degenerates without pregnancy.
Uterine Endometrial Changes
- Menstrual Phase (days 1–5): Shedding of uterine lining.
- Proliferative Phase (days 6–14): Endometrial regeneration and thickening under estrogen influence.
- Secretory Phase (days 15–28): Progesterone prepares endometrium for implantation.
Circulating Factors
- Endocrine: Hormones
- Ovarian estrogen and progesterone regulate conception, influencing growth factors, transcription factors, cytokines, cell cycle regulators.
- Estrogen prepares uterus, promotes endometrial growth and PR expression.
- Progesterone (post-ovulation) supports gland secretion, facilitates implantation window.
- Species differences exist.
- Human Chorionic Gonadotropin (hCG): Secreted by embryo, regulating trophoblasts, maternal tissues.
Interleukin (IL)-1α and β, IGF I and IGF II
- IL-1 plays a role in embryo implantation in response to a receptive endometrium, triggering a cytokine wave.
- IGFBP-1 moderates IGF1 and IGF2 effects, affects mitosis and metabolism; localizes to stromal cells; interacts with IGF2 Synthesized by trophoblasts.
- Both IGF2 and IL-1β can inhibit IGFBP-1+ activity
- MUC1 and Osteopontin involved in implantation.
Implantation Process
- Uterine preparation by progesterone.
- Blastocyst activation by factors (e.g., HB-EGF).
- Adhesion and invasion regulated by integrins, laminin, MMPs.
- Decidualization of stromal cells supports implantation.
Extracellular Vesicles (EVs)
- Nano-sized vesicles (exosomes, microvesicles, apoptotic bodies) carrying DNA, RNA, and proteins.
- Maternal-fetal communication, modulate implantation and receptivity, regulate immunity, promote angiogenesis.
- miRNAs (e.g., miR-30d) enhance adhesion; proteins like LIF, VEGF aid receptivity and angiogenesis.
Cell Cleavage
- Rapid mitotic divisions of the zygote form a morula.
- Typically starts 24-30 hours post-fertilization.
- Blastomeres form.
- Types: holoblastic, meroblastic.
Blastulation
- Follows cleavage.
- Forms blastocoel (fluid-filled cavity).
- Transforms from morula to blastocyst.
- Crucial for subsequent implantation.
Blastocyst Structure
- Blastocoel cavity: Fluid-filled space, essential for cell migration and differentiation, implantation.
- Inner Cell Mass (ICM): Cluster of cells, source of embryonic stem cells, forms embryo proper.
- Trophoblast: Outer layer, crucial for implantation and placenta formation.
- Zona pellucida: Glycoprotein layer, protects embryo, prevents polyspermy, degenerates during blastocyst's formation (replaced with trophoblast), allows for implantation.
Decidualization
- Transformation of endometrial stromal cells into decidual cells.
- Progesterone driven process, independent of pregnancy, critical for pregnancy maintenance.
Key Hormones in Implantation and Early Pregnancy
- Estrogen: Stimulates uterine epithelial cell proliferation and differentiation.
- Progesterone: Stimulates stromal cells, critical for pregnancy maintenance until placenta takes over.
- hCG: Prolongs progesterone secretion.
Implantation Failure
- Major limiting factor in ART success.
- Causes: Endometrial factors, embryonic factors.
The Sperm
- Common issues: Oligospermia, asthenospermia, teratospermia, azoospermia (obstructive/non-obstructive).
- Retrieval techniques: PESA, TESE.
The Oocyte
- Controlled ovarian hyperstimulation (COH) is important for ART.
- Monitoring includes ultrasound, serum estrogen, LH levels.
- Ovulation triggered with hCG.
- Egg retrieval ~36 hours post-hCG.
Stem Cells
- Self-renewal, potency (totipotent, pluripotent, multipotent), differentiation, and functions.
- Sources: pre-implantation, post-implantation embryos.
- Types: hES cells, iPSCs.
Pluripotency Testing
- Methods: Directed differentiation, functional assays.
- Functional tests are important for confirming pluripotency.
hES Cell Challenges
- Genetic instability (chromosomal abnormalities, mutations).
- Epigenetic alterations.
- Cancer risk.
Hypothalamic-Pituitary-Ovarian (HPO) Axis
- Critical endocrine system regulating female reproductive function.
- Components: Hypothalamus (GnRH), Pituitary gland (FSH, LH), Ovaries (estrogen, progesterone).
- Regulation: Negative and positive feedback mechanisms.
- Disruptions lead to reproductive issues (secondary sexual characteristics, fertility issues).
Ovarian Cycle
- Follicular development (primordial, primary, antral stages).
- Ovulation (LH surge completes meiosis I, follicle ruptures; releases secondary oocyte).
- Corpus luteum: Develops from remaining granulosa cells, produces progesterone, degenerates without pregnancy.
Endometrial Cycle
- Menstrual, proliferative, and secretory phases.
- Phases driven by hormonal changes (estrogen, progesterone) leading to endometrial changes, preparing for implantation.
Clinical Applications
- Contraception (COCP inhibits ovulation).
- Subfertility assessment, PCOS (Polycystic Ovarian Syndrome)
- Pregnancy and menopause: hCG, hormonal changes, HRT.
Implantation Window/Receptive Endometrium
- Brief period of endometrial receptivity.
- Hormonal influence (progesterone, estrogen).
- Morphological and cellular changes in the endometrium, with specific signaling.
- Duration of receptive endometrium (~3 days).
Embryo Metabolism
- Overview of metabolic processes supporting growth, development, implantation transiitons from anaerobic to more complex systems.
- Key stages (pre-compaction, blastocyst), metabolic processes (glucose, amino acid, fatty acid metabolism), metabolic regulation (insulin, growth factors, oxygen).
- Key shifts in metabolism throughout development.
- Nutrients used during development.
- Role of amino acids, including glycine buffering.
- Embryo viability and biomarkers, reflected in nutrients and secreted factors.
Sperm and Oocyte Viability
- Common issues like oligospermia, asthenospermia, and teratospermia in the sperm can impact the chances of successful fertilization.
- Monitoring ovarian reserve via FSH, LH, AMH levels and antral follicle counts is important for assessing reproductive potential in women, and to carefully plan for and implement the most appropriate ovarian stimulation protocols.
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Description
Explore the critical factors contributing to male infertility, including the impact of Reactive Oxygen Species (ROS) and DNA fragmentation on sperm quality. This quiz also covers advanced techniques such as cervical mucus migration tests and cryopreservation methods used in fertility treatments.