Study of Body Function - Sexual Reproduction

Sexual Reproduction

• Genes from two individuals combine randomly, creating genetic variation and adaptability.

• Germ cells (gametes: sperm and ova) are formed in gonads (testes and ovaries) via meiosis, which halves the chromosome number.

• Fertilization fuses ova and sperm, restoring the original chromosome number.

• The individual progresses from zygote to embryo to fetus.

Sex Determination

Autosomal and Sex Chromosomes

• Each zygote receives 23 chromosomes from each parent, totaling 23 pairs of homologous chromosomes (diploid number).

• 22 pairs are autosomal chromosomes with the same (but not identical) genes.

• The last pair are the sex chromosomes.

• Each autosomal chromosome has two alleles for each gene.

• Epigenetic changes in chromatin structure silence one allele, resulting in only one set of traits being expressed (Genomic imprinting).

Sex Chromosomes

• Females have two X chromosomes and always pass on an X chromosome.

• Males have an X and a Y chromosome and can pass on either.

• The sperm determines the sex of the child.

• The X chromosome has 1,090 genes, while the Y chromosome has only 80 genes.

• The Y chromosome contains testis-specific genes in palindrome areas.

• Mutations in X-linked genes cause 168 known diseases (linked to 113 X-linked genes).

X Chromosome Inactivation

• In females, one X chromosome is inactivated, forming a visible Barr Body.

• This inactivation is random, making a woman's cells a mosaic of paternal and maternal expression patterns.

• Not all genes on the inactivated X chromosome are totally inactive.

Formation of Testes and Ovaries

• Early embryonic gonads are identical in both sexes and can develop into either testes or ovaries.

• Testis-determining factor (TDF), coded by the SRY gene on the short arm of the Y chromosome, determines testes development.

• In XY embryos, seminiferous tubules form after TDF production.

• Germinal cells (become sperm) and Sertoli cells (supporting cells) differentiate 43 to 50 days post-fertilization.

• Leydig cells (testosterone-producing) appear around day 65, clustered in interstitial tissue between seminiferous tubules.

• Leydig cells begin producing large amounts of androgen (testosterone) about 8 weeks post-fertilization, stimulating the development of male reproductive organs.

• Testes descend into the scrotum for cooler temperatures needed for spermatogenesis; undescended testes are called cryptorchidism.

• In XX embryos, without TDF, ovaries develop; follicular cells appear in the second trimester.

Genetic Syndromes

• Kleinfelter’s syndrome: Males with 47 chromosomes (XXY).

• Turner’s syndrome: Females with only one sex chromosome (X) and 45 total chromosomes.

• Individuals with these conditions are genetically infertile and have lower sex hormone levels, along with other physiological issues.

Development of Accessory Sex Organs and External Genitalia

• Between days 25 and 50, embryos have Wolffian (mesonephric) ducts (can become male tract) and Müllerian (paramesonephric) ducts (can become female tract).

Duct Development

• Sertoli cells secrete anti-Müllerian hormone (AMH), causing Müllerian ducts to regress.

• Testosterone from Leydig cells stimulates Wolffian duct development into the epididymis, ductus deferens, seminal vesicle, and ejaculatory duct.

• Without AMH and testosterone, Müllerian ducts develop into uterine (fallopian) tubes and a uterus.

External Genitalia Formation

• Initially identical in both sexes for the first 6 weeks.

• Both sexes have a urogenital sinus, labioscrotal swelling, genital tubercle, and urethral folds.

• Testosterone masculinizes these into the scrotum, prostate gland, spongy urethra, and penis.

• Without testosterone, these become the labia and clitoris.

Masculinization

• Due to testosterone, which is converted to DHT (dihydroxytestosterone), the active hormone.

• DHT is essential for male external genitalia development and maintenance.

• Changes occur in brain development.

Disorders of Embryonic Sexual Development

Hermaphroditism

• Both ovarian and testicular tissue exist in the body.

• Some individuals have an ovary on one side and a testis on the other, while others have fused ovotestes.

• Caused by issues in zygotic mitosis where some cells receive the short arm of the Y chromosome with its SRY gene and some do not.

Pseudohermaphroditism

• Individuals have ovaries or testes, but accessory structures are incomplete or inappropriate for the genetic sex.

Female Pseudohermaphroditism

• May be due to excessive adrenal androgen secretion (congenital adrenal hyperplasia).

• Has both Müllerian and Wolffian duct derivatives but male external genitalia.

Male Pseudohermaphroditism

• May be due to testicular feminization syndrome where testes produce testosterone, but receptors don’t work.

• Female external genitalia form, but there is no uterus or fallopian tubes because the Müllerian duct degenerated.

• No male tract because the Wolffian duct was not stimulated.

• May also occur due to inability to make the enzyme 5α-reductase, which converts testosterone into DHT in target cells, needed for masculinization of external genitalia.

Endocrine Regulation of Reproduction

Introduction

• Testes cease testosterone production by the third trimester, and ovaries don't make embryonic sex hormones.

• Gonads of both sexes are relatively inactive at birth.

• Before puberty, sex hormones are present in low amounts.

• At puberty, the anterior pituitary begins releasing gonadotropic hormones.

Interaction Between Hypothalamus, Anterior Pituitary, and Gonads

• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are produced in the anterior pituitary glands of both males and females with three effects:

  • Stimulation of spermatogenesis or oogenesis

  • Stimulation of gonadal hormone secretion

  • Maintenance of the structures of the gonads

Regulation of FSH and LH

• Release of FSH and LH is controlled by the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus.

• Regulated by a negative-feedback loop where rising levels of gonadal hormone:

  • Inhibit GnRH release

  • Inhibit pituitary response to GnRH

Inhibin

• The gonads also secrete inhibin.

  • Secreted by Sertoli cells in testes

  • Secreted by granulosa cells of ovarian follicles

  • Specifically inhibits release of FSH (no effect on LH)

GnRH Secretion

• Secretion of GnRH is pulsatile, so FSH and LH are also pulsatile (more apparent in females than males)

  • Frequency of pulsations affects the target gland’s response

  • Kisspeptins are an excitatory neuropeptide that helps establish the cyclical female pattern of GnRH secretion.

  • Kisspeptins are suppressed by androgens in the male.

Onset of Puberty

• Secretion of FSH and LH is elevated at birth and stays high for the first 6 months of postnatal life; this declines to almost nothing until puberty.

• Puberty begins with a release of LH (pulsatile).

  • Due to declining sensitivity of the hypothalamus to negative feedback effects of gonadal hormones

  • This results in increases in testosterone or estradiol-17β secretion.

  • These hormones produce secondary sex characteristics.

Secondary Sex Characteristics

• In girls: growth spurt, breast development, menarche (first menstrual flow)

• In boys: later growth spurt; body, muscle, penis, and testis growth

• In both sexes: body hair is stimulated by androgens from adrenal gland at puberty

Age of Onset

• Depends on activity levels and amount of body fat

• Leptin secreted by adipose cells is required for the onset of puberty.

• Exercise may inhibit GnRH secretion.

• More active, slimmer girls begin puberty later.

• Melatonin from the pineal gland may play a role, but this is not proven in humans.

Human Sexual Response

• Four phases:

  • Excitation: characterized by increased muscle tone, vasocongestion of sexual organs; also called arousal

  • Plateau: continued vasocongestion

  • Orgasm: contraction of the uterus/vagina and male ejaculatory organs

  • Resolution: body returns to pre-excitation condition; men experience a refractory period where they are not able to ejaculate

Male Reproductive System

Testes

• Have two compartments:

  • Seminiferous tubules: where spermatogenesis occurs. FSH receptors are found on Sertoli cells, and FSH influences spermatogenesis.

  • Interstitial tissue: where Leydig (interstitial endocrine) cells make testosterone and are filled with blood and lymphatic capillaries. LH receptors are found on Leydig cells, and testosterone is secreted in response to LH.

Control of Gonadotropin Secretion

• LH secretion is controlled by rising testosterone secretion through negative feedback.

• FSH secretion is controlled by testosterone and inhibin secretion. Inhibin is released from the Sertoli cells of the seminiferous tubules.

Testosterone Derivatives

• Testosterone is converted to its derivatives in its target cells.

  • Converted by 5α-reductase to DHT, other androgens, 3α-diol and 3β-diol

  • Converted to estradiol-17β by aromatase enzyme; estradiol is used to effect testosterone inhibit LH secretion and for masculinization of the male brain.

  • Male and female brains are different – due to the effects of testosterone and estradiol

Testosterone Secretion and Age

• Negative feedback effects of testosterone and inhibin maintain a relatively constant secretion of gonadotropins in males

• Androgen secretion declines slowly in males to a hypogonadal state by age 70

• Other factors that affect testosterone secretion are physical inactivity, obesity, and drugs

Endocrine Functions of the Testes

• Androgens (anabolic steroids) – see Table 20.4 slide

• Estradiol

  • Secreted by Sertoli cells, Leydig cells, and developing sperm

  • Receptors for estradiol are on Sertoli and Leydig cells, cells lining the ducts, and accessory glands

  • Role in spermatogenesis, regulating the environment of developing sperm, fluid reabsorption, and sealing epiphyseal plates

Spermatogenesis

• Germ cells from the yolk sac migrate to the testes early in embryonic development.

  • Diploid spermatogonia first go through mitosis to increase the number of cells

  • One of the daughter cells (the primary spermatocyte) continues through meiosis; the other daughter cell remains a spermatogonial cell

  • After meiosis I → 2 secondary spermatocytes.

  • After meiosis II → 4 spermatids

  • Process occurs as the cells move toward the lumen of the seminiferous tubules

Spermiogenesis

• Maturation of spermatids into functioning spermatozoa

  • Protamines replace histones associated with DNA, inducing compaction of chromatin; the nucleus changes shape, and a flagellum develops

  • Cytoplasm removed by Sertoli cells, an acrosome, a cap of digestive enzymes, forms, and mitochondria concentrated in spirals in the mid-piece

Sertoli Cells

• Sperm development requires Sertoli cells.

  • Sertoli cells create a blood-testis barrier controlling what can enter the seminiferous tubules and preventing the immune system from developing antibodies against the sperm.

  • They also secrete FAS ligand, which binds to an FAS receptor on T cells, stimulating apoptosis; this creates an immunologically privileged site.

• Sertoli cells envelop the developing sperm.

  • They phagocytose some of the spermatid cytoplasm in spermiogenesis creating residual bodies.

  • They secrete androgen-binding protein (ABP) into the seminiferous tubule lumen. This binds to testosterone and concentrates it in the tubule. ABP production is stimulated by FSH; only Sertoli cells have FSH receptors, and testosterone stimulates spermatogenesis and spermiogenesis.

Hormonal Control

• Testosterone, or its derivatives, is required to stimulate meiosis and early spermatid maturation.

• Testosterone is secreted by the Leydig cells after stimulation by LH.

• FSH enhances spermatogenesis through the action of the Sertoli cells that are stimulated to make ABP, which concentrates the testosterone levels.

• FSH ensures optimal fertility

Male Accessory Sex Organs

• Spermatids move from the seminiferous tubules → rete testis → efferent ductules → epididymis.

• The epididymis is the site of sperm maturation and storage; sperm become motile

• In ejaculation, spermatozoa move from the epididymis → ductus deferens → ejaculatory duct → urethra.

• The seminal vesicle and prostate gland add fluid to the sperm to form semen.

  • Seminal fluid: contains fructose (energy for sperm)

  • Prostate fluid: contains citric acid, calcium, and vesiculase

    • Vesiculase is an enzyme that causes semen to coagulate after ejaculation

    • Fibrinolysis cause the semen to then become more liquid, freeing the sperm

Benign Prostatic Hyperplasia

• Benign prostatic hyperplasia (BPH) is a common disorder affecting 40 to 50% of men in their 50’s and 80% of men in their 80’s.

• The growth of the prostrate gland constricts the urethra decreasing urine flow.

• Drug treatments include decreasing dihydrotestosterone with 5α-reductase inhibitors, as well as α1-adrenergic receptor blockers.

Erection, Emission, and Ejaculation

Erection

• Results from blood flow into erectile tissues of the penis: corpora cavernosa and corpus spongiosum

• Due to parasympathetic nerve−induced vasodilation of the arterioles leading to the corpora cavernosa

• Nitric oxide serves as the neurotransmitter.

  • Activates guanylate cyclase to produce cGMP → Closes Ca^{2+} channels → Decreases cytoplasmic Ca^{2+} levels → Relaxes muscles

• Venous outflow of blood is partially blocked during an erection.

• Controlled by the hypothalamus and the sacral region of the spinal cord.

• Can also occur due to conscious sexual thought (hypothalamus → spinal cord → penis) or sensory stimulation (penis → spinal cord → penis)

Emission and Ejaculation

• Emission is the movement of semen into the urethra.

• Ejaculation is the forceful expulsion of semen from the urethra.

• Both are under sympathetic nervous system control.

• Contraction of smooth muscles in the tubules, seminal vesicle, prostate, and muscles at base of penis is involved in ejaculation.

Erectile Dysfunction

• Erectile dysfunction is the inability to produce or sustain an erection sufficient for intercourse.

• This can be caused by both physiological (heart disease, atherosclerosis etc.) and psychological problems (stress and depression).

• Common treatments include phosphodiesterase (PDE) 5 inhibitors like sildenafil (Viagra) and tadalafil (Cialis).

• These prevent the breakdown of cGMP and to promote erection.

Male Fertility

• Approximate semen volume for each ejaculation is 1.5 to 5.0 mL.

• There are generally 60 to 150 million sperm per milliliter of ejaculate.

• A sperm count < 20 million/ml semen is called oligospermia and is considered less fertile, it may be caused by heat, drugs, or anabolic steroids.

Male Contraception

• Vasectomy

  • Most widely used and reliable form of male contraception

  • The vas deferens is cut and tied to prohibit sperm transport.

  • A vasectomy does not affect testosterone production or ejaculation.

  • 70% of men develop antisperm antibodies

• Other methods of contraception

  • Condoms

  • Suppressing FSH, GnRH, LH—research is ongoing

  • Calcineurin—interferes with sperm motility and fertilization

  • Vasalgel—an injected gel placed in the vas deferens to block sperm transport

Female Reproductive System

Female Reproductive Organs

• Ovaries: female gonads; site of oocyte and sex steroid production

• Uterine (Fallopian) tubes: have fimbriae that partially wrap around the ovaries and “catch” the oocyte after ovulation; most common site of fertilization

• Uterus: site of embryonic development

  • Endometrium: inner layer, where embryo implants and develops; made of the stratum basale and stratum functionale

  • Myometrium: middle muscle layer; contracts to expel baby at birth

  • Perimetrium: outer connective tissue layer

  • Cervix: narrow bottom region of uterus

• Vagina: organ of copulation, opens between the labia (majora and minora)

• Clitoris – erectile tissue

Uterine Fibroids

• Uterine fibroids (leiomyomas) are benign tumors that form in the uterine smooth muscle (myometrium).

• They are extremely common; 70 to 80% of women have at least one by age 50.

• Their growth is stimulated by estrogen and progesterone.

• They have a variety of symptoms based on number and size.

Ovarian Cycle

Primary Oocytes

• Toward the end of gestation, a female’s oogonia begin meiosis to produce primary oocytes. Oogenesis is stopped at prophase I of meiosis I.

• The ovaries of a newborn girl have 2 million primary oocytes, By puberty, this number is cut to about 400,000, and only about 400 of these will be ovulated in her lifetime

Follicles

• Primary oocytes are contained within primary follicles that have one layer of cells.

  • In response to FSH, some of the primary follicles grow to produce many layers of granulosa cells.

  • Some develop fluid-filled vesicles called secondary follicles and secrete anti-Müllerian hormone that can be measured in preparation for in vitro fertilization

• Continued growth results in fused vesicles to form a single antrum; this is a mature Graafian follicle.

  • Cell layers called the corona radiata and zona pellucida form around the oocyte; these serve as a barrier for sperm entry.

  • Continued development of one Graafian follicle occurs because of stimulation from FSH, estradiol, and paracrine signals.

Secondary Oocytes

• As the Graafian follicle grows, the primary oocyte finishes meiosis I to become a secondary oocyte (plus a polar body, which soon degenerates).

• The secondary oocyte begins meiosis II but stops at metaphase II; meiosis II will complete only if there is fertilization of the ovum.

Ovulation

• By the 10th to 14th day after the first day of menstruation, one follicle becomes a mature Graafian follicle.

• Other secondary follicles regress and become atretic, a type of apoptosis resulting from hormones and paracrine regulators of androgens and FAS ligands, and a mature Graafian follicle is protected from atresia and forms a bulge on the surface of the ovary.

• The surviving Graafian follicle becomes so big it bulges out of the ovary.

  • Hormones stimulate the follicle to burst and release the secondary oocyte. If not fertilized, the oocyte will degenerate after a few days.

Corpus Luteum

• After ovulation, the remaining follicle becomes a corpus luteum (yellow body), which secretes both estradiol and progesterone; these hormones play a role in the menstrual cycle and maintaining a pregnancy.

• Toward the end of a non fertile cycle, the corpus luteum regresses to a nonfunctional corpus albicans.

Pituitary-Ovarian Axis

• Anterior pituitary secretes FSH and LH controlled by GnRH and negative feedback from ovarian hormones.

• Aside from stimulating the development of the follicles, FSH stimulates estradiol production in the follicles; the bigger the follicle, the more estradiol it releases.

• FSH and LH secretions are not equal and affect the pulse frequency of GnRH

Menstrual Cycle

Introduction

• Describes the 28-day cycle of endometrial buildup and sloughing in response to ovarian hormones

• Three phases: menstrual, proliferative, and secretory.

• Changes in the endometrium follow changes in the follicles of the ovaries.

Cyclic Changes in the Ovaries

• Follicular changes in the ovaries can be broken into three phases: follicular phase, ovulation, luteal phase

Ovarian Follicular Phase

• Lasts from day 1 through 13 (variable).

• Primary follicles → Secondary follicles → Graafian follicle (one kept).

• Characterized by increasing levels of estradiol production from granulosa cells, reaching a high around day 12.

• Initiated by FSH, which also upregulates the number of FSH receptors on the follicles, increasing sensitivity to FSH.

• At the end of this phase, FSH and high levels of estradiol stimulate production of LH receptors in the Graafian follicle; increased estradiol also stimulates the hypothalamus to release more GnRH, leading to LH release from the anterior pituitary called the LH surge.

Ovulation

• FSH causes the Graafian follicle to bulge out of the ovary wall; LH surge begins ~24 hours before ovulation and stimulates Graafian follicle to rupture, releasing secondary oocyte.

Ovarian Luteal Phase

• After ovulation, LH stimulates the ruptured follicle to become a corpus luteum.

  • The corpus luteum secretes estradiol and progesterone; progesterone peaks ~1 week after ovulation

  • High levels of estradiol and progesterone feed back on the pituitary gland and inhibit FSH and LH secretion; there may also be inhibin production, which helps inhibit FSH.

  • Shuts down follicle development to prevent further ovulation long enough to give the secondary oocyte a chance to be fertilized

• Ends with the degeneration of the corpus luteum around day 28; decreasing levels of estradiol and progesterone stimulate the sloughing of the endometrium and menstruation.

Cyclic Changes in the Endometrium

• The menstrual cycle begins with menstruation at the end of the previous ovarian cycle; the development of the endometrium is regulated by secretion of estradiol and progesterone in the ovaries

Proliferative Phase

• Occurs while ovary is in the follicular phase.

• Increasing levels of estradiol stimulate the growth of the stratum functionale of the endometrium.

• Spiral arteries develop, and the endometrium also becomes more vascular and develops progesterone receptors.

Secretory Phase

• Occurs while the ovaries are in the luteal phase.

• Secretion of progesterone stimulates the development of uterine glands, which store glycogen.

• The endometrium also becomes even thicker and more vascular and is prepared to nourish a growing embryo if the oocyte is fertilized.

Menstrual Phase

• Occurs as a result of the fall in estradiol and progesterone when the corpus luteum degenerates.

• Arteries in the endometrium constrict, cells in the stratum functionale die, and this region is sloughed.

Polycystic Ovarian Syndrome (PCOS)

• PCOS is a common endocrine disorder in women.

• The cause is unknown but appears to be related to elevated levels of AMH in a pregnant woman that may promote increased LH secretion in the offspring to contribute to PCOS.

• The ovaries contain follicles that become fluid filled cysts and secrete excessive amounts of androgens.

• Symptoms include amenorrhea, dysmenorrhea, reduced fertility, excessive growth of body hair, male pattern baldness, acne, and insulin resistance.

Effects of Pheromones, Stress, and Body Fat

### Pheromones

• Pheromones (odor molecules) can synchronize the menstrual cycle (dormitory affect) and the olfactory system has input on GnRH neurons.

Stress

• Stress and emotions can affect the menstrual cycle; neurons from the limbic system input to GnRH neurons, and stress can cause amenorrhea (lack of menstruation)

Body Fat

• Low body fat can produce delayed menarche or amenorrhea (lack of menstruation) controlled by leptin.

Functional Amenorrhea

• Cessation of menstruation caused by inadequate FSH and LH from inadequate GnRH and comes from intense physical exercise, stress, and very low body fat.

Contraceptive Methods

Contraceptive Pill

• Includes synthetic estradiol and progesterone.

• Acts like a prolonged luteal phase produces negative-feedback inhibition of GnRH, so ovulation never occurs, and the endometrium still proliferates.

• Placebo pills are taken for 1 week to allow menstruation. Newer pills have reduced risk for endometrial and ovarian cancers and reduction of osteoporosis

Vaginal Ring and Contraceptive Patch

• Deliver contraceptive steroids through a mucous membrane or skin and permit lower dosage than oral contraceptives.

Long-Acting Reversible Contraceptives (LARC)

• Intrauterine devices (IUDs) – prevent fertilization

• Subdermal hormonal implants – contain progestin that inhibits ovulation and thickens cervical mucus

Rhythm Method of Contraception

• Pregnancy is unlikely as long as a couple has sex more than 6 days before ovulation and more than 1 day after.

• A woman can time ovulation by taking her temperature and this is a pretty good indicator for when ovulation occurs but not a very reliable form of birth control.

Menopause

• Characterized by cessation of ovarian activity and menses due to changes in the ovaries, not to decreases in FSH and LH, and FSH and LH levels are actually elevated due to lack of negative feedback; usually occurs after age 50.

• Symptoms are due to loss of estradiol.

  • Hot flashes are produced by vasomotor disturbances, the walls of the urethra and vagina atrophy, and vaginal glands no longer produce lubrication.

  • After menopause, risk for atherosclerosis and osteoporosis increases.

Menopause and Osteoporosis

• Estradiol is needed for bone deposition, so menopausal women are at increased risk for osteoporosis.

  • Adipose tissue does make a weak form of estradiol called estrone; heavier women have a reduced risk of osteoporosis

Fertilization, Pregnancy, and Parturition

Introduction

• Over 300 million sperm enter the female at ejaculation and only about 100 of these live to enter the fallopian tube, with only 10% able to fertilize an ovum

• In order to fertilize the ovum, a sperm must become capacitated, taking at least 7 hours after ejaculation with pH increases and hyperactivation of the flagellum due to progesterone and the opening of CatSper channels; capacitated sperm are guided to the oocyte by chemotaxis and thermotaxis

Fertilization

• Fertilization usually occurs in the uterine tubes.

• The association between the acrosome cap and zona pellucida cells stimulates the entry of Ca^{2+} and then the release of acrosomal enzymes.

  • These enzymes allow the sperm to “digest” the zona pellucida on its way into the oocyte.

• When the sperm fuses with the oocyte, it releases phospholipase C that results in Ca^{2+} release and a calcium wave travels through the oocyte to the opposite side from the entry of the sperm

  • The Ca^{2+} has several effects:

    • Prevents other sperm from entering the oocyte (polyspermy)

    • Activates the oocyte to finish meiosis to become a haploid ovum

• Twelve hours after the sperm enters the oocyte, the nuclear envelope around the ovum disappears, and chromosomes join to form a diploid zygote.

  • Monozygotic (identical) twins – single ovum splits

  • Dizygotic (fraternal) twins – 2 eggs are fertilized by 2 sperm

• Sperm contributes ½ chromosomes, centrosome, and mitochondria (eliminated by autophagy), and the egg contributes ½ chromosomes, cytoplasm, all other organelles.

In Vitro Fertilization (IVF)

• IFV starts by the woman undergoing hormone injections to hyperstimulation the ovarian follicles.

• The oocytes are then harvested and they are fertilized through intracytoplasmic sperm injection.

• They are then allowed to develop for three to five days and then transferred to the uterus; multiple embryos are usually introduced which can lead to increased numbers of multiple births.

• This process has allowed millions of otherwise infertile couples to have babies.

Cleavage and Blastocyst Formation

Prenatal Human Development

• Prenatal human development is divided into two stages:

  • Embryo – from zygote (fertilized egg) to 8 weeks after fertilization

  • Fetus – 8 weeks through parturition (childbirth)

• Cleavage of the zygote begins 30 to 36 hours after fertilization, characterized by rapid mitosis, which forms a ball of cells called a morula, which enters the uterus about 3 days after fertilization

  • Division continues and forms a hollow ball of cells called the blastocyst, which has two parts:

    • Inner cell mass which will become the fetus.

    • Trophoblast will become the chorion → placenta

Implantation

• On the sixth day after fertilization, the trophoblast cells secrete an enzyme that allows the blastocyst to “eat” into the endometrium; the side containing the inner cell mass goes in first, and by the seventh to tenth day, the blastocyst is completely buried.

Embryonic Stem Cells and Cloning

• Cells of early cleavage are totipotent and will divide to become every cell in the body; a cloned blastocyst can be created by implanting a somatic cell into an ovum cytoplasm in a process called somatic cell nuclear transfer, successful in sheep, dogs, horses, and other animals, but not in humans.

• Inner cell mass cells cultured in vitro are called embryonic stem cells and are pluripotent = able to become any type of cell in the body and form the three embryonic germ layers.

  • Ectoderm – epidermis and neural tissue

  • Mesoderm – connective tissue and muscle

  • Endoderm – epithelium of lungs and gut

  • These cells might be used therapeutically to treat diabetes type I, Parkinson disease, or spinal cord injury

Adult Stem Cells

• Found in the hippocampus, subventricular zone of the brain, intestinal crypts, bulge of the hair follicle, and bone marrow and are multipotent = can give rise to several types of related cells; do not jump across embryonic germ layers.

• Induced pluripotent stem (IPS) cells – adult fibroblast cells changed into pluripotent stem cells using retroviruses; could serve many purposes.

• Regenerative medicine – developing future medical treatments using stem cells

Implantation of the Blastocyst and Formation of the Placenta

Chorionic Gonadotropin (hCG)

• While implantation occurs, the blastocyst releases chorionic gonadotropin, which acts like LH to keep the corpus luteum functional by to continue releasing estradiol and progesterone, also keeps the endometrium thick and vascular to house the blastocyst, prevents menstruation; secretion of hCG declines by the 10th week as the placenta takes over hormone production to maintain the pregnancy.

• Pregnancy tests use monoclonal antibodies against the beta unit of hCG to detect hCG presence in the blood or urine.

Chorionic Membranes

• From day 7 to day 12, the chorion splits into the cytotrophoblast (inner) and syncytiotrophoblast (outer); the developing cytotrophoblast and inner cell mass are separated by the amniotic cavity.

• The inner cell mass of the blastocyst becomes the endoderm (will become the gut organs) and ectoderm (will become the skin and nervous system); the mesoderm develops later and will become the muscles, bones, and connective tissues.

• The syncytiotrophoblast secretes protein- digesting enzymes and creates blood-filled cavities in the endometrium; the cytotrophoblast sends villi into these pools of maternal blood, forming the chorion frondosum, and the developing placental structures are an “immunologically privileged site.