PHGY1030 - Male Reproduction_2025

Sex Differentiation

• Embryonic Development:

  • XX (female): NO SRY gene

  • XY (male): presence of SRY gene initiates testis differentiation

  • Testes secrete:

    • Anti-Müllerian Hormone (AMH) from Sertoli cells

    • Testosterone from Leydig cells

Hormonal Regulation

• HPG Axis Activity:

  • Hormones involved:

    • Testosterone (T)

    • Estradiol (E2)

• Hormonal levels change throughout lifespan in both males and females.

Puberty Factors

• Genetically influenced

• Diet and nutrition considerations

• Environmental exposures (e.g., endocrine disruptors such as Bisphenol A)

• Stress factors continue to be researched.

Hypothalamic-Pituitary-Testis Axis

• Key hormones:

  1. Kisspeptin

  2. Gonadotropin-releasing hormone (GnRH)

  3. Follicle-stimulating hormone (FSH)

  4. Luteinizing hormone (LH)

  5. Androgens (T, DHT)

  6. Low levels of Estrogen (E2)

• Functions:

  • Spermatogenesis

  • Regulation of secondary sexual characteristics

  • Functionality of organs (bones, muscles, etc.)

Regulation Mechanisms

• Negative Feedback:

  1. T and DHT regulate pituitary and hypothalamic signals.

  2. Inhibin B from Sertoli cells limits FSH production, affecting sperm formation.

Androgen Biosynthesis and Distribution

• Leydig cells synthesize testosterone.

• Dihydrotestosterone (DHT) is derived from testosterone via 5α-reductase enzyme.

• Androgen-Binding Proteins (ABP) concentrate testosterone in seminiferous tubules.

• 98-99% of circulating testosterone bound to Sex Hormone Binding Globulin (SHBG).

• Monitoring SHBG levels is crucial for assessing bioavailable testosterone.

Importance of Estrogens in Males

• Functionality:

  • Aromatase provides for the production of E2 essential for spermatogenesis and overall male health (muscle, bone, cardiovascular).

Androgens in Females

• DHEA/S serves as precursor androgens.

• Adrenal glands are primary androgen sources in females, affecting ovary and sexual function health.

Androgen Receptor (AR)

• Mechanism for T and DHT signal transmission:

  • Changes gene expression and cell function.

• Estrogen receptors (ERα and ERβ) operate similarly for estrogen signaling.

Reproductive Anatomy

Internal Structures

• Testes

• Epididymis

• Vas deferens

• Seminal vesicles

• Prostate

External Structures

• Penis

• Scrotum

Spermatogenesis Overview

• Process: Spermatogonia (2n) develop into spermatocytes (haploid) and ultimately into spermatozoa (mature gamete).

• Sertoli cells nourish and maintain support for spermatogenesis.

Mature Spermatozoon Structure

• Integrated into seminal fluid, which supports functional motility (contains PSA).

• Normal sperm count is around 60-100 million spermatozoa per mL.

• Microscopic semen analysis assists in diagnosing causes of infertility.

Age-Related Changes in Male Reproductive Function

• Testosterone levels decline (~1% per year after age 30) leading to changes:

  • Increased SHBG levels

  • Decreased muscle mass and bone density

  • Erectile dysfunction

Part 2: Male Reproductive Disorders

Common Disorders in Males

• Infertility:

  • Causes include problems with spermatogenesis and reproductive tract function.

  • Associated conditions:

    1. Hypogonadism (T/DHT deficiency)

    2. Lifestyle risk factors (diet, obesity, smoking)

    3. Environmental exposures

    4. Medications causing hormonal imbalances

• Prostate Disorders:

  • Benign Prostatic Hyperplasia (BPH)

  • Prostate cancer

Diagnosing and Treating Male Infertility

• Diagnoses may be idiopathic or linked to other disorders like thyroid issues.

• Treatment approaches depend on the physical exam and lab analysis:

  • Hormonal therapy, assisted reproductive technologies (ART), and lifestyle changes.

Benign Prostatic Hyperplasia (BPH)

• Occurs in aging males (50-80% incidence in men aged 50-80).

• Symptoms: Difficult urination, frequent nocturia, weak urine stream.

• Treatment options: Surgery or medications such as 5α-reductase inhibitors.

Prostate Cancer Overview

• Most common cancer in men (~12% incidence).

• Symptoms include difficulty with urination and pain.

• Diagnosis involves screening (PSA levels, biopsy).

• Survival rates are high due to slow growth.

Prostate Cancer Therapies

• Focus on androgen deprivation therapies targeting AR signaling.

• Current therapies include:

  • Anti-androgens

  • GnRH agonists/antagonists

  • Combining multiple approaches due to treatment challenges.

Review Questions for Male Reproductive Physiology

1. What controls male sex differentiation?

2. Identify T-producing cells and their locations.

3. What are the cells that support spermatogenesis, and which hormones regulate them?

4. Describe the function of the Androgen Receptor.

5. Explain the chromosomal changes during spermatogenesis.

6. Why is PSA important in clinical settings?

7. How does male reproductive function evolve with aging?

8. Outline primary therapies used for prostate cancer.