Clevage

Infertility and Assisted Reproductive Technologies (ART)

  • Infertility definition: the inability to conceive a child or carry to birth.
  • About $75\%$ of causes can be identified; examples include:
    • Diseases such as sexually transmitted diseases that can cause scarring of reproductive tubes in men or women.
    • Developmental problems often related to abnormal hormone levels in one individual.
    • Inadequate nutrition, especially starvation, which can delay menstruation.
    • Stress: short-term stress can affect hormone levels; long-term stress can delay puberty and cause less frequent menstrual cycles.
    • Other factors: toxins (e.g., cadmium), tobacco smoking, marijuana use, gonadal injuries, aging.
  • Assisted reproductive technologies (ART) available when infertility is identified; common type is in vitro fertilization (IVF):
    • Eggs are collected from the woman after extensive hormonal treatments that prepare mature eggs and the uterus for implantation.
    • Sperm are obtained from the man; eggs and sperm are combined outside the body and supported through several cell divisions to ensure viability of zygotes.
    • When embryos reach the eight-cell stage ($8$-cell stage), one or more are implanted into the woman’s uterus.
    • If fertilization is not accomplished by simple IVF, intracytoplasmic sperm injection (ICSI) can be used (sperm is injected directly into an egg).
  • IVF yields a surplus of fertilized eggs/embryos that can be frozen for future use; procedures can result in multiple births.
  • Ethical/clinical note: IVF/ART involve ethical considerations and regulatory questions; refer to professional guidelines for practice.

Fertilization

  • Fertilization: union of gametes (egg and sperm) to form a zygote; one egg must fuse with one sperm to maintain diploidy (one complete diploid set).
  • Egg protection: in mammals, the egg is surrounded by the zona pellucida (glycoprotein matrix).
  • Acrosomal reactions: when a sperm binds to the zona pellucida, acrosomal enzymes break down the zona pellucida to allow sperm–egg fusion; sperm plasma membrane fuses with the egg plasma membrane, transferring the sperm nucleus into the ovum.
  • Nuclear fusion: egg and sperm nuclei break down their membranes; the two haploid genomes condense to form a diploid genome.
  • Prevention of polyspermy: after the acrosomal reaction at a location on the egg membrane, the egg releases proteins elsewhere to prevent other sperm from fusing with the egg; failure leads to polyspermy which yields a non-viable embryo that dies within a few days.

Cleavage and Blastula Stage

  • Cleavage: rapid, successive cell divisions of the zygote without growth in mass, producing a blastula with more than $>100$ cells.
  • Blastula structure: a spherical layer of cells (the blastoderm) surrounding a fluid-filled or yolk-filled cavity (the blastocoel).
  • Mammals form a structure called the blastocyst, characterized by:
    • An inner cell mass (embryoblast) that will form the embryo.
    • An outer layer called the trophoblast that will contribute to the placenta and nourish the embryo.
  • During cleavage, each cell is a blastomere.
  • Two developmental states in mammals:
    • The inner cell mass (embryoblast) contains embryonic stem cells that will differentiate into the various cell types.
    • The trophoblast forms the placenta and nourishes the embryo.
  • Cleavage modes depending on yolk content:
    • Holoblastic (total) cleavage: occurs when there is little yolk, as in placental mammals (including humans).
    • Meroblastic (partial) cleavage: occurs when there is abundant yolk, as in birds.

Gastrulation and Germ Layers

  • Gastrulation: formation of the body plan; the blastula reorganizes to form three germ layers that differentiate into organ systems:
    • Ectoderm: gives rise to the nervous system and epidermis.
    • Mesoderm: gives rise to muscle cells and connective tissue.
    • Endoderm: gives rise to columnar cells in the digestive system and many internal organs.

Organogenesis and Vertebrate Formation

  • Organogenesis: organs form from germ layers through differentiation; embryonic stem cells express specific gene sets that determine cell fates.
  • Model organisms in developmental studies:
    • Drosophila (fruit fly): segmented bodies; helps study patterning and organogenesis along the body axis.
    • C. elegans (nematode): ~1000 somatic cells; fate of each cell tracked; low variation in lineage.
  • Vertebrate neural system formation:
    • Ectoderm differentiates: edge cells receive growth-factor signals to become epidermis; center cells form the neural plate.
    • If signaling is disrupted, ectoderm tends to neural tissue.
    • Neural plate folds to form the neural tube, which becomes the brain and spinal cord.
  • Mesoderm derivatives:
    • Lateral to the neural tube, mesoderm forms somites with interspaces; somites develop into ribs, lungs, and segmental (spinal) muscles.
    • Mesoderm forms the notochord, a rod-shaped structure that forms the central axis of the body.

Vertebrate Axis Formation

  • Body axes in vertebrates: lateral-medial (left-right), dorsal-ventral (back-belly), and anterior-posterior (head-feet).
  • Spemann–Mangold experiment: dorsal cells transplanted into the belly region of another embryo induced a second notochord at the transplanted site, indicating dorsal cells are programmed to define the axis and form the notochord.
  • Genes and axis formation: many genes are implicated in axis formation; mutations can disrupt symmetry and proper development.
  • Internal asymmetry: external body symmetry is visible, but internal organs are asymmetrical (e.g., heart on the left, liver on the right); left-right axis establishment is an early developmental process still under active study.

Reproductive Ethics and Technologies (PGD and Designer Babies)

  • Designer babies concept: genetic engineering of a human child to select desirable traits (disease resistance, sex, attractiveness, strength, intelligence).
  • PGD (Prenatal Genetic Diagnosis) in IVF:
    • Screening of embryos produced via IVF for specific genetic alleles that cause diseases (e.g., sickle cell disease, muscular dystrophy, hemophilia).
    • PGD involves diagnosis, selection, and implantation of the chosen embryos.
    • Unaffected embryos can be implanted; unaffected embryos can be donated to science or discarded.
  • Ethical considerations and debate:
    • Expense and access: PGD is expensive and not typically covered by insurance; only a small percentage of live births use such technologies.
    • Varied ethical views on embryo discarding; some argue that life begins at conception, making discarding embryos unacceptable under any circumstances.
    • Sex selection controversies: some countries ban sex selection for non-disease reasons; others permit for family balancing; U.S. remains with varied approaches.
    • Some disabled parents may wish to select embryos sharing their disability, citing cultural or positive aspects, which raises ethical tensions with the principle of beneficence vs. non-maleficence (Primum non nocere: first, do no harm).
    • Policy and regulation: debates on whether to regulate these technologies now or in the future; uncertainty about affordability and accessibility.
  • Broader implications: rapid advance of reproductive technologies prompts ongoing discussion about eugenics risks and the potential for new ethical frameworks in medicine and society.

Organogenesis and Vertebrate Formation (Continued)

  • Recap on organogenesis: germ layers differentiate into organ systems via regulated gene expression and signaling cascades.
  • Neural axis formation and vertebrate body plan establishment involve coordinated signaling, tissue movements, and gene regulation; disruptions can lead to developmental abnormalities.
  • Overall learning outcomes: understanding fertilization, cleavage, gastrulation, organogenesis, germ layers, axis formation, and the ethical context of modern reproductive technologies such as IVF, ICSI, PGD, and embryo selection.