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 (D)</p> Signup and view all the answers

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

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

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

<p>Hot flashes and night sweats (A)</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 (D)</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 (A)</p> Signup and view all the answers

What characterizes Polycystic Ovarian Syndrome (PCOS)?

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

What is the role of hCG in early pregnancy?

<p>Maintains the corpus luteum and progesterone production (C)</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 (B)</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 (A)</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. (C)</p> Signup and view all the answers

How does cryopreservation affect sperm functionality?

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

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

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

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

<p>Anaerobic glycolysis (B)</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. (C)</p> Signup and view all the answers

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

<p>Buffers intracellular pH (A)</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 (D)</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 (A)</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. (C)</p> Signup and view all the answers

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

<p>Cortical reaction (B)</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 (C)</p> Signup and view all the answers

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

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

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

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

What happens to the oocyte immediately after sperm penetration?

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

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

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

How does the acrosome reaction facilitate fertilization?

<p>By releasing digestive enzymes (B)</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. (D)</p> Signup and view all the answers

Which nutrient is predominantly utilized during the early preimplantation stage?

<p>Lactate (A)</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. (D)</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. (D)</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. (B)</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) (B)</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. (A)</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. (D)</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. (C)</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. (A)</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. (A)</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. (D)</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. (D)</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. (C)</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. (D)</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. (B)</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 (A)</p> Signup and view all the answers

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

<p>Progesterone (A)</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 (B)</p> Signup and view all the answers

What is the effect of progesterone on stromal cells?

<p>Triggers decidualization in the endometrium (D)</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 (C)</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 (B)</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 (D)</p> Signup and view all the answers

Which factor is NOT typically associated with implantation failure?

<p>Polyspermy during fertilization (D)</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 (A)</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 (B)</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 (A)</p> Signup and view all the answers

Which hormone is synthesized by trophoblast cells during early pregnancy?

<p>hCG (C)</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 (B)</p> Signup and view all the answers

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

<p>Progesterone (D)</p> Signup and view all the answers

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

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

What role does progesterone play following ovulation?

<p>Supports gland secretion (C)</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 (B)</p> Signup and view all the answers

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

<p>Exosomes (A)</p> Signup and view all the answers

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

<p>HB-EGF (B)</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 (C)</p> Signup and view all the answers

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

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

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

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

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

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

What type of cell forms the placenta during embryonic development?

<p>Trophoblast (C)</p> Signup and view all the answers

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

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

What is the primary function of osteopontin in embryonic implantation?

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

What occurs during the hatching phase of the blastocyst?

<p>Zona pellucida breakdown (D)</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. (A)</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. (D)</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. (B)</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. (C)</p> Signup and view all the answers

Which event characterizes the completion of meiosis in the oocyte?

<p>Release of the second polar body. (D)</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. (B)</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. (A)</p> Signup and view all the answers

Which factors can influence epigenetic profiles throughout life?

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

Which of the following describes the acrosome reaction?

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

Which event occurs during the hatching stage of implantation?

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

What role does calcium oscillation play post-fertilization?

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

Which stage immediately follows the sperm-oocyte fusion?

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

During what phase does luteinizing hormone surge to trigger ovulation?

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

Flashcards

What is the role of Reactive Oxygen Species (ROS) in male fertility?

Reactive oxygen species (ROS) are molecules that can damage cells. While they are needed for some sperm functions, excess ROS causes problems like poor sperm movement, abnormal shape, DNA damage, and cell death.

What is Cryopreservation?

A process used to freeze and preserve sperm cells, usually involving cooling, freezing, and thawing with special chemicals.

What is Vitrification?

A rapid cooling technique for preserving sperm cells, which prevents ice crystal formation and improves sperm survival by avoiding the use of freezing agents.

What is a Cervical Mucus Migration Test?

This test mimics the natural female reproductive tract to assess sperm movement and viability.

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What is Capacitation?

This process prepares sperm for fertilization. Changes occur within the uterus or oviduct, enabling sperm to interact with the egg.

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What is Sperm DNA Fragmentation?

DNA damage in sperm, which can affect fertility. It's not easily repaired by sperm, but the egg can try to fix it.

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What is Sperm Transport?

This process is a series of events involving several factors, from sperm being deposited in the vagina through their journey to the oviduct.

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Where does fertilization occur?

This part of the female reproductive tract is the meeting place for the sperm and egg.

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Metabolism

The process of converting food into usable energy for cells. Includes breaking down carbohydrates, fats, and proteins.

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Aerobic Metabolism

A type of metabolism that uses oxygen to produce energy. More efficient but slower.

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Anaerobic Metabolism

A type of metabolism that doesn't require oxygen. Less efficient but faster.

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Fatty Acid Oxidation

The process of breaking down fats to release energy. Particularly important during later stages of development.

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Insulin

A hormone that enhances the uptake of glucose by cells.

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Growth Factors

Hormones that stimulate growth and metabolism.

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Pre-implantation

The stage of development before implantation in the womb. The embryo relies on maternal nutrients.

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Post-implantation

The stage of development after implantation in the womb. The embryo's metabolic demands increase.

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TCA Cycle (Krebs Cycle)

The cycle that breaks down glucose to produce energy. Requires oxygen and occurs in mitochondria.

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Embden-Meyerhof Pathway

The process of breaking down glucose without oxygen. Occurs in the cytoplasm.

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Cell Cleavage

The process of rapid cell division in the early embryo.

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Blastulation

The stage where the embryo forms a fluid-filled cavity called the blastocoel.

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Blastocoel Cavity

The fluid-filled cavity inside the blastocyst.

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Trophoblast

The outer layer of the blastocyst, which will eventually develop into the placenta.

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Inner Cell Mass

The inner cell mass of the blastocyst, which will develop into the embryo itself.

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Sperm Capacitation

A series of changes that sperm undergo after ejaculation, enhancing their ability to fertilize an oocyte. This process involves removal of glycoprotein coats and changes in the sperm membrane, leading to increased motility and the ability to undergo the acrosome reaction.

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Acrosome Reaction

The release of enzymes from the acrosome (a cap-like structure on the sperm) upon reaching the zona pellucida (the outer layer of the oocyte). These enzymes digest the zona pellucida, allowing the sperm to penetrate.

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Sperm-Oocyte Fusion

The fusion of the sperm and oocyte membranes, allowing the sperm nucleus to enter the oocyte and create a zygote.

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Cortical Reaction

A reaction triggered by the sperm entering the oocyte, where cortical granules release their contents into the perivitelline space, modifying the zona pellucida to prevent further sperm entry, ensuring fertilization by only one sperm.

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Completion of Meiosis in the Oocyte

The completion of the second meiotic division of the oocyte upon fertilization, resulting in the formation of a second polar body and the mature ovum, contributing half of the genetic material to the zygote.

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Zygote Formation

The fusion of the sperm nucleus and the oocyte nucleus, resulting in a diploid cell containing genetic material from both parents. This marks the beginning of the development of the embryo.

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Zona Pellucida (ZP)

The outer layer of the oocyte, composed of glycoproteins (ZP1, ZP2, ZP3, ZP4 in humans). ZP3 and ZP4 are crucial for sperm binding and triggering the acrosome reaction.

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Blastocyst Hatching

The process by which the blastocyst (the early embryo) escapes from the zona pellucida, exposing the trophoblast (outer layer responsible for implantation) for interaction with the uterine lining.

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Blastocyst Apposition

The initial, loose contact between the blastocyst and the endometrial surface, occurring during the 'receptive window' (6-10 days post-ovulation) when the uterine lining is prepared for implantation.

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Blastocyst Adhesion

The firm attachment of the blastocyst to the endometrium through specific cell surface receptors (integrins, cadherins, selectins).

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Pinopodes

Projections on the endometrial surface that increase its area and help absorb fluid, bringing the blastocyst closer for implantation. These are regulated by progesterone and estrogen.

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Blastocyst Invasion

The invasion of the endometrium by trophoblast cells, establishing connections between the mother and fetus.

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Cytotrophoblast

Proliferative precursor cells within the trophoblast that contribute to its growth.

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Syncytiotrophoblast

Invasive, multinucleated cells arising from the cytotrophoblast, responsible for digesting the maternal extracellular matrix for deep embedding of the embryo into the uterine lining.

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Epigenetic Reprogramming

The period of time during early development when the epigenome undergoes significant changes, primarily through methylation and demethylation.

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Epigenome

The sum of all the epigenetic modifications to DNA and chromatin, influencing gene expression.

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Luteal Phase

The phase in the menstrual cycle after ovulation. The ruptured follicle turns into the corpus luteum, which produces progesterone. If pregnancy doesn't occur, the corpus luteum degenerates into the corpus albicans.

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Menstrual Phase

The shedding of the uterine lining due to low progesterone and estrogen levels. It marks the beginning of a new menstrual cycle.

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Proliferative Phase

The phase where the uterine lining regenerates and thickens under the influence of estrogen. It prepares the uterus for a potential pregnancy.

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Secretory Phase

The phase where the endometrium is prepared for implantation by progesterone. Glands secrete nutrients for a fertilized egg.

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Ovarian Estrogen & Progesterone

Hormones produced by the ovaries responsible for regulating the menstrual cycle and influencing cell growth and activity in the uterus.

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Estrogen Role

The hormone that prepares the uterus for pregnancy by promoting endometrial growth and the expression of progesterone receptors.

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Progesterone Role

The hormone that supports gland secretion after ovulation and allows for the implantation window by creating a receptive environment for the embryo.

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Interleukin (IL)-1

A key component of the immune system that aids in embryo implantation by stimulating the production of other cytokines and preparing the endometrium.

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Human Chorionic Gonadotropin (hCG)

Hormone secreted by the embryo that plays a role in implantation by affecting both the embryo and the maternal tissues.

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Mucin 1 (MUC1)

A protein that acts as a barrier during the early stages of pregnancy but is reduced locally at the implantation site to allow the embryo to attach.

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Osteopontin

A protein regulated by progesterone that supports adhesion of the embryo to the uterine lining.

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Uterine Preparation

The process where the uterus undergoes changes to become receptive for implantation.

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Cleavage Stage

The stage where the fertilized egg rapidly divides, forming a solid ball of cells called a morula.

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Compaction

The tight junctions between the cells in the morula that are essential for subsequent differentiation and polarization of cells.

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Formation of the Blastocoele

The fluid-filled cavity formed inside the morula, transforming it into a blastocyst.

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Corpus Luteum

A temporary gland that forms from the follicle after ovulation. It produces progesterone, which prepares the uterine lining for pregnancy.

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Endometrial Cycle

The cycle of changes in the uterine lining (endometrium) that occur during a menstrual cycle. It involves three phases: menstrual, proliferative, and secretory.

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hCG (Human Chorionic Gonadotropin)

Hormone produced by the implanted embryo, which maintains the corpus luteum, ensuring a healthy pregnancy.

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Window of Implantation

The period of time (6-10 days after fertilization) when the endometrium is most receptive for implantation. It is critical for successful pregnancy.

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Receptive Endometrium

The uterine lining in a prepared state to receive a fertilized egg (blastocyst), essential for successful implantation. It occurs during the luteal phase.

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Menopause

The process by which the ovary stops ovulating and producing hormones, ending menstruation. This marks the end of a woman's reproductive years.

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Hormone Replacement Therapy (HRT)

Hormone therapy used to replace declining hormones in women going through menopause. It helps relieve symptoms and prevent osteoporosis. However, there are potential risks.

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What is the Inner Cell Mass (ICM)?

A cluster of cells found at one pole of the blastocyst. It's the source of embryonic stem cells and eventually develops into the embryo proper and some extraembryonic tissues.

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What is the Trophoblast?

The outer layer of cells surrounding the blastocyst. It plays a critical role in implantation into the uterine wall and develops into part of the placenta.

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What is the Zona Pellucida?

A glycoprotein layer that surrounds the oocyte and early embryo. It protects the embryo and prevents fertilization by multiple sperm.

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What is Decidualization?

The transformation of endometrial stromal fibroblasts into secretory decidual cells. It happens independently of pregnancy and is driven by progesterone.

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What is Decidualization?

A process that occurs in the luteal phase of the menstrual cycle, independent of pregnancy. It is driven by progesterone and involves changes in the endometrial lining.

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What is the role of Estrogen in implantation?

Stimulates proliferation and differentiation of uterine epithelial cells.

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What is the role of Progesterone in implantation?

Stimulates stromal cells, crucial for sustaining pregnancy until the placenta takes over (around 12 weeks).

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What is the role of hCG in implantation?

A hormone synthesized by trophoblast cells. It prolongs progesterone secretion, which is essential for early pregnancy.

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What is Implantation Failure?

A major limiting factor in assisted reproductive technology (ART) success. It can be caused by factors in the endometrium, the embryo, or both.

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What is Oligospermia?

A low sperm count, which can affect male fertility.

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What is Asthenospermia?

Poor sperm motility, meaning the sperm can't move properly.

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What is Teratospermia?

Abnormal sperm morphology, meaning the sperm have irregular shapes.

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What is Azoospermia?

The absence of sperm in the semen, which can make it impossible to conceive naturally.

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What is PESA?

A procedure to retrieve sperm from the epididymis, a coiled tube near the testicle.

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What is TESE?

A procedure to retrieve sperm directly from the testicle.

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What is the HPO axis?

The Hypothalamic-Pituitary-Ovarian (HPO) axis is a complex system of hormones and organs that control female reproductive function, encompassing the menstrual cycle, ovulation, and fertility.

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What is the role of the hypothalamus in the HPO axis?

The hypothalamus is the command center of the HPO axis, responsible for releasing gonadotropin-releasing hormone (GnRH), which triggers the pituitary gland to release its own hormones.

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

The pituitary gland, located at the base of the brain, responds to GnRH by releasing follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which directly influence the ovaries.

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What is the function of FSH in the HPO axis?

Follicle-stimulating hormone (FSH) is responsible for stimulating the growth and maturation of ovarian follicles, which contain developing eggs. It also plays a role in regulating the menstrual cycle.

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What is the function of LH in the HPO axis?

Luteinizing hormone (LH) triggers ovulation, the release of a mature egg from the ovary. It also stimulates the production of estrogen and progesterone by the ovaries.

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How does the HPO axis regulate itself?

The HPO axis relies on a delicate balance of hormones and feedback mechanisms. Estrogen and progesterone produced by the ovaries can negatively regulate the hypothalamus and pituitary, controlling the release of GnRH, FSH, and LH.

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What is the role of positive feedback in the HPO axis?

When estrogen levels reach a certain threshold, they can positively feedback on the pituitary, causing a surge in LH and triggering ovulation.

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What can happen if the HPO axis is disrupted?

Disruptions to the HPO axis, such as stress, hormonal imbalances, or certain medical conditions, can lead to irregular menstrual cycles, anovulation, fertility issues, or delayed puberty.

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What is the ovarian cycle?

The ovarian cycle encompasses the maturation of ovarian follicles, the release of an egg during ovulation, and the subsequent hormonal changes that prepare the body for potential pregnancy.

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What are primordial follicles?

Primordial follicles are immature follicles and the earliest stage of follicular development. They contain primary oocytes surrounded by a single layer of granulosa cells.

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What are the stages of follicular development?

During follicular development, follicles progress from primordial to primary and then to antral stages. Antral follicles are characterized by a fluid-filled cavity called the antrum.

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How is ovulation triggered?

As follicles mature, they secrete increasing amounts of estrogen, which leads to a surge in LH. This LH surge triggers ovulation.

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What happens during ovulation?

The LH surge causes the mature follicle to rupture, releasing the secondary oocyte into the fallopian tube, where fertilization can occur.

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What is the role of estrogen in the female body?

Estrogen, produced by the ovaries, plays a crucial role in the regulation of the menstrual cycle, secondary sexual characteristics, and bone health.

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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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