Human Reproductive System: Gamete Production & Hormonal Control
Gonads: Primary Reproductive Organs
Female Gonads: Ovaries
Male Gonads: Testes
Primary Functions of Gonads
- Gametogenesis: Production of gametes (reproductive cells) from germ cells.
- Gametes: Reproductive cells
- Ova: Female gametes
- Spermatozoa: Male gametes
- Sex Hormone Secretion: Gonadal steroids including androgens, estrogens, and progesterone.
Accessory Reproductive Organs
- Ducts for Gamete Transport:
- Males: Epididymis, vas deferens, ejaculatory ducts
- Females: Ovarian tubes (fallopian tubes)
- Glands Secreting into Ducts:
- Males: Seminal vesicles and prostate gland
Gametogenesis: The Production of Gametes
What are Gametes?
Gametes are the reproductive cells.
Gametogenesis Stage 1: Mitosis
Mitosis: Germ Cell Proliferation
- Cell division creates two daughter cells from an original primordial germ cell.
- Each daughter cell contains 23 paired chromosomes.
- The purpose is to create a population of germ cells for future gametogenesis.
Timing of Mitosis in Gametogenesis
- Males: Primary spermatocytes form during the embryonic period; mitosis increases after puberty and sustains throughout life.
- Females: Primary oocytes are all formed during fetal development.
Epigenetic Fetal Programming
The in utero environment affects physiological function in offspring.
Gametogenesis Stage 2: Meiosis
During meiosis, germ cells develop into mature gametes.
Meiosis: Two Cell Divisions
Meiosis involves a sequence of two cell divisions, resulting in haploid gametes. Fertilization then forms a diploid zygote.
Key Stages of Meiosis
- Chromosome Replication: Begins with a primary spermatocyte or primary oocyte. Each of the 46 chromosomes produces a copy of itself.
- Crossing Over: Exchange of genes between homologous chromosome pairs. This allows for mixing and matching of maternal and paternal genes, resulting in genetic variation.
- First Meiotic Division: Cells divide, and each daughter cell receives either the maternal or paternal sister chromatids of each chromosome (223 possible combinations).
- Males: Results in two secondary spermatocytes.
- Females: Results in one secondary oocyte and one first polar body.
- Second Meiotic Division: Sister chromatids divide into two daughter cells.
- Males: Results in four spermatids; this process is continuous after puberty.
- Females: Results in a zygote and a second polar body; the second meiotic division occurs following fertilization.
Summary of Gametogenesis
- Mitosis: Germ Cells develop into spermatogonia (males) or oogonia (females).
- Primary Spermatocyte / Oocyte: Undergo crossing over and the first meiotic division.
- Secondary Spermatocyte / Oocyte: Undergo the second meiotic division.
- End Result: Four spermatids (males) or one zygote (females, after fertilization).
Genotypic Sex Determination
The complete genetic composition of an individual is their genotype. Sex is determined by sex chromosomes:
- Males: XY genotype
- Females: XX genotype
Phenotypic Sex Differentiation
The appearance and function of an individual is their phenotype. Sex differentiation refers to the development of the reproductive system in the fetus.
- Ducts:
- Males: Vas deferens
- Females: Fallopian tubes
- External Genitalia:
- Males: Penis
- Females: Vagina
Embryonic Development and Gonadal Differentiation
- Differentiation of the Gonads (Weeks 1-5)
- Differentiation of the Gonads (Week 6)
Gonadal Differentiation: Weeks 1-5
- Gonadal Ridge: Develops into testes or ovaries.
- Wolffian Ducts: Develop into epididymis and vas deferens.
- Müllerian Ducts: Develop into fallopian tubes.
Gonadal Differentiation: Week 6
The SRY gene is expressed at this time. Located on the Y chromosome (Sex-determining Region of Y chromosome), it produces SRY protein, which leads to testes development, including Sertoli and Leydig cells. In the absence of the SRY gene, ovaries develop.
Male Internal and External Genitalia Differentiation
- Testosterone: Induces Wolffian duct formation, leading to male reproductive “tubes.” Dihydrotestosterone (DHT) also plays a crucial role.
- Anti-Müllerian Hormone (AMH): Induces Müllerian duct degeneration.
Female Internal and External Genitalia Differentiation
- Absence of AMH: Müllerian ducts develop, forming the ducts of the female reproductive system.
- Absence of Testosterone: Wolffian ducts degenerate. Female external genitalia develop due to the lack of DHT.
Androgen Insensitivity Syndrome (AIS)
Individuals with AIS are genotypic males with testes, but present with a female phenotype for external genitalia. The issue is defective androgen receptor binding, resulting in the degeneration of both duct systems.
Congenital Adrenal Hyperplasia (CAH)
CAH can lead to the virilization of an XX fetus. Androgens secreted from the adrenal cortex result in ambiguous or masculinized external genitalia.
Sex Hormone Synthesis
Cholesterol: Precursor to Sex Hormones
Cholesterol is the precursor to all sex hormones. The general metabolic conversion pathway is: Cholesterol → Progesterone → Androgens → Estrogens.
Androgens
Androgens are secreted by the testes, ovaries, and the adrenal cortex (e.g., DHEA).
Estrogens and Progesterone
- Progesterone: Primarily secreted by the ovaries and placenta.
- Estrogens: Secreted by ovaries, testes, placenta, and body fat (via androgen conversion). Estradiol is the primary estrogen in the blood.
Control of Sex Hormone Secretion: The HPG Axis
The Hypothalamic-Pituitary-Gonadal (HPG) axis controls sex hormone secretion, involving:
- Hypothalamus
- Anterior Pituitary Gland
- Gonads
Hypothalamus
The hypothalamus secretes Gonadotropin-Releasing Hormone (GnRH).
Anterior Pituitary Gland
The anterior pituitary gland secretes gonadotropins:
- Follicle-Stimulating Hormone (FSH)
- Luteinizing Hormone (LH)
Gonads
The gonads (ovaries and testes) are the target organs.
Sex Hormones in Both Sexes
Sex hormones are secreted by the ovaries and testes in response to FSH and LH. They are also secreted by the adrenal cortex.
Testosterone Secretion and Effects
When the HPG axis is activated, testosterone has a local effect on spermatogenesis and acts as a masculinizing hormone at receptors.
Female Sex Hormone Control
In females, LH binds to theca cells, stimulating them to create androgens, which are then converted into estrogen.
Hormone Levels Across the Lifespan
Hormone levels fluctuate throughout the lifespan. Both sexes secrete both types of hormones, but at different levels.
Testicular Function
- Spermatogenesis: Occurs in the seminiferous tubules.
- Androgen Secretion: Primarily testosterone.
Key Testicular Cells
The primary testicular cells are Sertoli and Leydig cells.
Sertoli Cells
Sertoli cells line the seminiferous tubules, function in spermatogenesis, and respond to FSH.
Leydig Cells
Leydig cells are located in the interstitium, secrete testosterone, and respond to LH.
Spermatogonia: Male Germ Cells
Spermatogonia are the male germ cells.
Sperm Structure
Sperm have four main parts:
- Acrosome
- Head
- Midpiece
- Flagellum
Acrosome
The acrosome is at the tip of the head and contains hydrolytic enzymes for penetration of the oocyte.
Head
The head contains the DNA.
Midpiece
The midpiece contains mitochondria.
Flagellum
The flagellum is the tail that propels sperm through the female reproductive tract.
Role of Sertoli Cells in Spermatogenesis
Sertoli cells extend from the basement membrane to the lumen of the seminiferous tubules. Their tight junctions form the blood-testis barrier. Spermatogonia mature through mitosis between the basement membrane and Sertoli cells, and spermatogenesis is completed in the lumen.
Functions of Sertoli Cells
- Nutrient delivery to developing sperm cells.
- Secretion of most of the fluid within the seminiferous tubules.
- Secretion of Androgen-Binding Protein (ABP).
- Secretion of paracrine agents for proliferation and differentiation of spermatogonia.
- Secretion of inhibin, which provides negative feedback control for FSH.
- Secretion of Müllerian-Inhibiting Substance (MIS) during the fetal period.
Factors Affecting Sperm Development
- Sperm Count: Inhibited by elevated scrotal temperature.
- Abnormal Sperm Morphology: Can be affected by radiation, lead, pesticides, THC, alcohol, smoking, and diet.
Sperm Transport Pathway
Sperm are transported from the seminiferous tubules to the epididymis (where they are stored), then to the vas deferens, to the ejaculatory ducts, and finally to the urethra.
Semen Composition
The seminal vesicles and prostate gland secrete the bulk of the semen, providing nutrients, buffers, chemicals to increase mobility, and prostaglandins.
Erection
Erection is the increased rigidity of the penis due to vascular engorgement.
Neurally-Mediated Events of Erection
- Inhibition of sympathetic activity.
- Non-adrenergic, non-cholinergic ANS neurons release nitric oxide (NO).
- Dilation of arterioles.
- Compression of veins.
Ejaculation
Ejaculation is the discharge of semen from the penis, a spinal reflex mediated by sympathetic activity.
Ejaculation: Emission Phase
The emission phase involves smooth muscle contraction of the epididymis, vas deferens, ejaculatory duct, prostate, and seminal vesicles.
Ejaculation: Expulsion Phase
The expulsion phase involves smooth muscle contraction in the urethra and skeletal muscles at the base of the penis to expel semen.
Role of FSH in Male Reproduction
FSH signals Sertoli cells to produce more paracrine agents that stimulate spermatogenesis. It also increases ABP production, which raises testosterone concentration in the seminiferous tubules.
Role of LH in Male Reproduction
LH stimulates Leydig cells to secrete testosterone. Testosterone acts as a paracrine agent, facilitating spermatogenesis within the seminiferous tubules, and is important for systemic hormonal effects.
Systemic Responses to Testosterone Secretion
- Puberty: Development of male secondary sexual characteristics.
- Conversion to Other Sex Hormones:
- DHT: Affects the prostate gland.
- Estradiol: Influences the brain, skeleton, and body fat.
- Other Systemic Effects: Male pattern baldness, aggressiveness, muscle and skeletal development, and increased liver production.
HPG Axis Feedback Control in Males
- Testosterone: Inhibits LH secretion at both the hypothalamus and the anterior pituitary.
- Inhibin: Produced by Sertoli cells, inhibin inhibits FSH production by the anterior pituitary. Inhibin levels are high when sperm count is high.
Andropause (Male Menopause)
Andropause refers to decreased testicular testosterone secretion in older age, typically beginning around age 40. It is caused by deteriorating testicular function and reduced ability to respond to FSH and LH.
The Female Reproductive Cycle
Menstrual Cycle Overview
The menstrual cycle averages 28 days and encompasses both the ovarian cycle and the uterine (menstrual) cycle.
- Ovarian Cycle: Cyclical changes in the ovaries involving the maturation and release of one gamete, along with hormone secretion.
- Uterine (Menstrual) Cycle: Cyclical changes in the uterus to create an environment favorable for zygote implantation.
Ovaries: Primary Reproductive Organs
The ovaries are the primary female reproductive organs.
Female Reproductive Tract
- Fallopian Tubes: Site of fertilization.
- Uterus: Site of zygote implantation.
- Cervix
- Vagina
Ovarian Functions
- Oogenesis
- Maturation of oocytes
- Ovulation
- Sex steroid hormone secretion
Oogenesis
Oogenesis is the production of female gametes during the fetal period.
Maturation of Oocytes
Maturation of oocytes occurs following puberty.
Ovulation
Ovulation is the expulsion of a mature oocyte from the ovary.
Ovarian Sex Steroid Hormone Secretion
The ovaries secrete estrogen, progesterone, inhibin, and small amounts of testosterone.
Oogenesis: Female Gamete Production
Oogenesis is the production of female gametes. Oogonia proliferate via mitosis, then differentiate into primary oocytes during fetal life. The first meiotic division begins in utero but is then arrested until ovulation.
First Meiotic Division in Oogenesis
This division is completed just before ovulation. One daughter cell receives all the cytoplasm, forming the secondary oocyte. The other becomes a non-functional first polar body.
Second Meiotic Division in Oogenesis
This division occurs in the fallopian tube if the egg is fertilized. One daughter cell receives all the cytoplasm, forming a zygote. The other becomes the second polar body. The zygote then travels to the uterus for possible implantation.
Oocyte Maturation and Ovulation Timeline
Oocyte maturation and ovulation begin at puberty and end at menopause.
Ovarian Cycle Phases
The ovarian cycle is a series of events associated with the maturation and release of an egg, consisting of two main phases:
- Follicular Phase (Days 1-14): A single mature follicle and secondary oocyte develop and are released.
- Luteal Phase (Days 15-28): The period from ovulation until the degeneration of the corpus luteum.
Follicular Phase Details
- Oocytes Exist in Follicles: A primordial follicle contains a primary oocyte surrounded by a single layer of granulosa cells. Granulosa cells support the developing oocyte and secrete estrogen, inhibin, and small quantities of progesterone.
- Development into Primary Follicles: This involves oocyte growth and proliferation of multiple layers of granulosa cells, leading to increased blood estrogen levels. The zona pellucida also develops, enhancing sperm binding to the oocyte surface.
- Development of Antral Follicles: These follicles contain a primary oocyte, multiple layers of granulosa cells, the zona pellucida, theca cells, and an antrum (fluid-filled cavity).
- Maturation of Antral Follicles: At the start of each menstrual cycle, 10-25 antral follicles begin to mature. After one week, all but one undergo atresia (degeneration). The one remaining dominant follicle is released, and its first meiotic division results in a secondary oocyte.
Luteal Phase: Corpus Luteum Formation
Following ovulation, the remaining follicular cells transform into the corpus luteum, an endocrine structure that lasts 10-14 days if pregnancy does not occur. The corpus luteum secretes estrogen, progesterone, and inhibin.
Ovulation Process
Ovulation typically occurs on day 14 of the menstrual cycle and is triggered by the LH surge. The wall of the dominant follicle fuses with the ovarian wall and ruptures due to enzymatic digestion. The secondary oocyte, along with its surrounding granulosa cells and zona pellucida, is then released into the fallopian tube.
Hormonal Control of the Ovarian Cycle
Early Follicular Phase Hormones
During the early follicular phase, LH stimulates theca cell proliferation and androgen production. FSH stimulates granulosa cells to convert these androgens to estrogen.
Middle Follicular Phase Hormones
Rising estrogen levels inhibit the secretion of LH and FSH. Inhibin also preferentially inhibits FSH. Estrogen, primarily from granulosa cells, contributes to this feedback. Decreased FSH leads to the atresia (dying off) of less developed follicles.
Late Follicular Phase and LH Surge
When a threshold level of plasma estrogen is reached, the feedback control on the anterior pituitary switches from negative to positive. This triggers the release of stored LH and FSH just before day 14, causing the characteristic LH and FSH surge.
Effects of the Estrogen-Mediated LH Surge
The estrogen-mediated LH surge induces:
- Completion of the first meiotic division, producing a secondary oocyte.
- Follicle rupture (ovulation).
- Corpus luteum formation, leading to the secretion of progesterone and estrogen.
Luteal Phase Hormones and Feedback
Following ovulation, the corpus luteum secretes progesterone, estrogen, and inhibin. These hormones inhibit GnRH, LH, and FSH secretion.
Uterine (Menstrual) Cycle Phases
The uterine cycle is a series of cyclical changes in the uterine endometrium, driven by cyclical changes in hormone secretion by the ovaries and corpus luteum. It consists of three phases:
- Menstrual Phase
- Proliferative Phase
- Secretory Phase
Menstrual Phase (Days 1-5)
During days 1-5, ovarian hormones and gonadotropins are at their lowest levels. Menstruation is triggered by decreased plasma estrogen and progesterone levels. The uterus sheds all but the deepest layers of the endometrium, with blood and detached tissue flowing out of the vagina.
Proliferative Phase (Days 5-14)
This phase spans from day 5 to day 14, ending with ovulation. During this time, estrogen stimulates:
- Endometrial growth, vasculature growth, and enlargement of the glands.
- Production of progesterone receptors by endometrial cells.
- Thinning of cervical mucus to facilitate the passage of sperm.
Secretory Phase
The secretory phase corresponds with the luteal phase. During the early secretory phase, progesterone is responsible for:
- Converting the estrogen-primed endometrium into a secretory tissue.
- Inhibiting uterine contractions.
- Making cervical mucus relatively protective against bacteria.
Hormonal Birth Control Mechanisms
Hormonal birth control methods prevent ovulation and uterine changes that would otherwise facilitate implantation.
Systemic Effects of Estradiol
- Brain: Temperature regulation, protective against dementia, promotes physical activity drive.
- Cardiovascular System: Increases nitric oxide (NO) production, decreases platelet aggregation.
- Liver: Improves cholesterol profile by increasing HDLs and decreasing LDLs.
- Bone: Favorable effects to maintain bone mineral density.
Menopause
Menopause is characterized by the depletion of viable ovarian follicles, leading to decreased estrogen and progesterone secretion, and compensatory increases in FSH and LH secretion.