Male Infertility and Sperm Analysis
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Questions and Answers

What is the primary hormone produced by the corpus luteum to maintain the uterine lining?

  • Progesterone (correct)
  • Estrogen
  • FSH
  • hCG
  • During which phase of the menstrual cycle does the endometrium first begin to shed?

  • Proliferative Phase
  • Secretory Phase
  • Follicular Phase
  • Menstrual Phase (correct)
  • What occurs to the corpus luteum if pregnancy does not happen?

  • It stimulates further follicular development
  • It degenerates into the corpus albicans after 14 days (correct)
  • It transforms into the blastocyst
  • It continues progesterone production indefinitely
  • Which phase of the endometrial cycle is characterized by rising estrogen levels and preparation for implantation?

    <p>Proliferative Phase</p> Signup and view all the answers

    What is the approximate duration of the window for implantation after fertilization?

    <p>6–10 days</p> Signup and view all the answers

    What is a recognized symptom of menopause due to hormonal changes?

    <p>Hot flashes and night sweats</p> Signup and view all the answers

    What is the primary inhibitory effect of the combined oral contraceptive pill (COCP)?

    <p>Inhibits ovulation through negative feedback on FSH and LH</p> Signup and view all the answers

    What change occurs to the endometrium during the secretory phase?

    <p>It produces nutrients for potential embryo support</p> Signup and view all the answers

    What characterizes Polycystic Ovarian Syndrome (PCOS)?

    <p>Polycystic ovaries and hyperandrogenism</p> Signup and view all the answers

    What is the role of hCG in early pregnancy?

    <p>Maintains the corpus luteum and progesterone production</p> Signup and view all the answers

    What are the consequences of excess Reactive Oxygen Species (ROS) on sperm?

    <p>Reduced sperm DNA integrity and increased cell death</p> Signup and view all the answers

    Which of the following factors are primarily linked to increased sperm DNA fragmentation?

    <p>High temperatures and fewer cysteines in Protamine 1</p> Signup and view all the answers

    What role does cervical mucus play in sperm transport?

    <p>It filters sperm, allowing passage only during the fertile window.</p> Signup and view all the answers

    How does cryopreservation affect sperm functionality?

    <p>50-60% sperm survive freezing with reduced functionality.</p> Signup and view all the answers

    During oocyte transport, which structure is responsible for capturing the oocyte after ovulation?

    <p>Fallopian tube fimbriae</p> Signup and view all the answers

    Which pathway primarily supports energy demands during the early preimplantation stages?

    <p>Anaerobic glycolysis</p> Signup and view all the answers

    What is the primary function of Protamine 1 in sperm?

    <p>It compacts DNA for stability and reduces DNA fragmentation.</p> Signup and view all the answers

    What is the main function of glycine in amino acid metabolism?

    <p>Buffers intracellular pH</p> Signup and view all the answers

    At which developmental stage do embryos begin to rely more heavily on glucose metabolism?

    <p>Morula to Blastocyst</p> Signup and view all the answers

    What is the main challenge associated with vitrification compared to traditional cryopreservation?

    <p>Risk of ice crystal formation</p> Signup and view all the answers

    Which statement accurately describes the process of sperm selection during transport?

    <p>Only morphologically normal sperm are retained in the oviduct.</p> Signup and view all the answers

    What process occurs first after the sperm binds to the oocyte's plasma membrane?

    <p>Cortical reaction</p> Signup and view all the answers

    What describes the composition of the morula during early embryonic development?

    <p>Composed of 16-32 smaller blastomeres</p> Signup and view all the answers

    What is a primary role of insulin in metabolic regulation during embryonic development?

    <p>Enhances glucose uptake</p> Signup and view all the answers

    Which factor is most critical to embryo viability during developmental stages?

    <p>Nutrient levels and metabolites</p> Signup and view all the answers

    What happens to the oocyte immediately after sperm penetration?

    <p>The second polar body forms</p> Signup and view all the answers

    Which metabolic pathway provides the embryo with energy during post-implantation stages?

    <p>Aerobic glycolysis</p> Signup and view all the answers

    How does the acrosome reaction facilitate fertilization?

    <p>By releasing digestive enzymes</p> Signup and view all the answers

    Which statement is true about the role of fatty acids in early embryo development?

    <p>They provide energy later as demands increase.</p> Signup and view all the answers

    Which nutrient is predominantly utilized during the early preimplantation stage?

    <p>Lactate</p> Signup and view all the answers

    What is the fate of the zygote after the fusion of sperm and oocyte nuclei?

    <p>It undergoes cleavage to form a multicellular embryo.</p> Signup and view all the answers

    What role does methylation play in fully differentiated cells?

    <p>It ensures specific genes for cell function remain active.</p> Signup and view all the answers

    What is a consequence of incomplete removal of methylation patterns during iPSC reprogramming?

    <p>Reduced reprogramming efficiency and limited pluripotency.</p> Signup and view all the answers

    Which hormone is secreted by the hypothalamus as part of the HPO axis?

    <p>Gonadotrophin Releasing Hormone (GnRH)</p> Signup and view all the answers

    How do estrogen and progesterone participate in the regulation of the HPO axis?

    <p>They exert negative feedback to regulate GnRH, FSH, and LH secretion.</p> Signup and view all the answers

    What potential impact does selective pressure in stem cell culture have?

    <p>Induction of chromosomal abnormalities or mutations.</p> Signup and view all the answers

    What phase does high estrogen concentration lead to during the menstrual cycle?

    <p>A surge in Luteinising Hormone triggering ovulation.</p> Signup and view all the answers

    Which of the following describes a possible disruption in the HPO axis?

    <p>Irregular menstrual cycles or anovulation.</p> Signup and view all the answers

    What characterizes the initial stages of ovarian follicles before they require FSH?

    <p>They develop without FSH influence.</p> Signup and view all the answers

    What happens to granulosa cells as they support a maturing follicle?

    <p>They initially lose FSH receptors as a secondary oocyte is released.</p> Signup and view all the answers

    Which assay method is most essential for confirming the pluripotency of iPSCs?

    <p>Functional assays like teratoma formation.</p> Signup and view all the answers

    In the context of iPSC differentiation, how can altered methylation influence outcomes?

    <p>It restricts the development of certain desired cell types.</p> Signup and view all the answers

    What defines the role of the pituitary gland in the HPO axis?

    <p>It responds to GnRH by releasing gonadotrophins.</p> Signup and view all the answers

    What important process occurs during the LH surge related to follicle maturation?

    <p>Secondary oocyte completes meiosis I.</p> Signup and view all the answers

    What is the primary function of the inner cell mass (ICM) in embryonic development?

    <p>Develops into the embryo and some extraembryonic tissues</p> Signup and view all the answers

    Which hormone is primarily responsible for supporting pregnancy until the placenta takes over?

    <p>Progesterone</p> Signup and view all the answers

    What characterizes the zona pellucida during the blastocyst stage?

    <p>It degenerates and is replaced by trophoblastic cells</p> Signup and view all the answers

    What is the effect of progesterone on stromal cells?

    <p>Triggers decidualization in the endometrium</p> Signup and view all the answers

    Which condition is characterized by a physical blockage preventing sperm from being present in semen?

    <p>Obstructive Azoospermia</p> Signup and view all the answers

    What is a common use for Controlled Ovarian Hyperstimulation (COH) in assisted reproduction?

    <p>To increase the production of multiple follicles for oocyte retrieval</p> Signup and view all the answers

    What type of stem cell can develop into almost any cell type but not extra-embryonic tissues?

    <p>Pluripotent stem cells</p> Signup and view all the answers

    Which factor is NOT typically associated with implantation failure?

    <p>Polyspermy during fertilization</p> Signup and view all the answers

    Which stage does the inner cell mass (ICM) come from in embryonic development?

    <p>Early pre-implantation embryos</p> Signup and view all the answers

    What best describes the function of trophoblast cells?

    <p>They play a role in implantation and placental formation</p> Signup and view all the answers

    What characteristic of stem cells allows them to self-renew?

    <p>Their capacity to divide and produce copies of themselves</p> Signup and view all the answers

    Which hormone is synthesized by trophoblast cells during early pregnancy?

    <p>hCG</p> Signup and view all the answers

    What is the significance of the antral follicle count in assessing ovarian reserve?

    <p>It reflects the number of visible follicles in the ovaries</p> Signup and view all the answers

    What is the primary hormone produced by the corpus luteum after ovulation?

    <p>Progesterone</p> Signup and view all the answers

    During which phase of the menstrual cycle does the endometrium thickens due to estrogen?

    <p>Proliferative Phase</p> Signup and view all the answers

    What role does progesterone play following ovulation?

    <p>Supports gland secretion</p> Signup and view all the answers

    What is the effect of interleukin-1 (IL-1) in the process of embryo implantation?

    <p>Promotes trophoblast adhesion</p> Signup and view all the answers

    What type of extracellular vesicles (EVs) are involved in maternal-fetal communication?

    <p>Exosomes</p> Signup and view all the answers

    What initiates the blastocyst's attachment and invasion into the endometrium?

    <p>HB-EGF</p> Signup and view all the answers

    What is the main characteristic of the cleavage stage in embryo development?

    <p>Morula formation with rapid divisions</p> Signup and view all the answers

    Which protein is crucial for cell compaction during early embryo development?

    <p>E-cadherin</p> Signup and view all the answers

    What is the significance of IGFBP-1 in late secretory phase endometrium?

    <p>Modulates IGF activity</p> Signup and view all the answers

    Which energy source is primarily used during the pre-compaction stage of embryo development?

    <p>Anaerobic nutrients</p> Signup and view all the answers

    What type of cell forms the placenta during embryonic development?

    <p>Trophoblast</p> Signup and view all the answers

    Which type of ion transport is essential for fluid movement into the blastocoele?

    <p>Sodium-potassium pumps</p> Signup and view all the answers

    What is the primary function of osteopontin in embryonic implantation?

    <p>Facilitates cell adhesion</p> Signup and view all the answers

    What occurs during the hatching phase of the blastocyst?

    <p>Zona pellucida breakdown</p> Signup and view all the answers

    What role do the glycoproteins ZP3 and ZP4 play in fertilization?

    <p>They mediate sperm binding and trigger the acrosome reaction.</p> Signup and view all the answers

    Which hormonal changes occur during the ovarian follicular phase?

    <p>Follicle-stimulating hormone stimulates follicular recruitment and growth.</p> Signup and view all the answers

    What happens immediately following sperm penetration of the zona pellucida?

    <p>The cortical reaction is triggered in the oocyte.</p> Signup and view all the answers

    How does the presence of progesterone affect the implantation process?

    <p>It regulates fluid absorption and increases endometrial surface area.</p> Signup and view all the answers

    Which event characterizes the completion of meiosis in the oocyte?

    <p>Release of the second polar body.</p> Signup and view all the answers

    What is a primary function of syncytiotrophoblast cells during implantation?

    <p>To digest maternal extracellular matrix for deep embedding.</p> Signup and view all the answers

    What specific physiological change occurs during sperm capacitation?

    <p>Enhanced motility and ability to undergo the acrosome reaction.</p> Signup and view all the answers

    Which factors can influence epigenetic profiles throughout life?

    <p>Environmental conditions, lifestyle, and medications.</p> Signup and view all the answers

    What is the fate of the zygote immediately after fertilization?

    <p>It will divide to become a multicellular embryo.</p> Signup and view all the answers

    Which of the following describes the acrosome reaction?

    <p>Digestive enzyme release for zona penetration.</p> Signup and view all the answers

    Which event occurs during the hatching stage of implantation?

    <p>The blastocyst escapes the zona pellucida.</p> Signup and view all the answers

    What role does calcium oscillation play post-fertilization?

    <p>It activates developmental processes within the oocyte.</p> Signup and view all the answers

    Which stage immediately follows the sperm-oocyte fusion?

    <p>Triggering of the cortical reaction.</p> Signup and view all the answers

    During what phase does luteinizing hormone surge to trigger ovulation?

    <p>Follicular phase.</p> Signup and view all the answers

    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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    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.

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