Male Reproductive Physiology Lecture 2 PDF

Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Lecture 2 Objectives: The student will be able to: Identify the hormones involved in spermatogenesis and their action. Describe the hormonal control of male repro...

Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Lecture 2 Objectives: The student will be able to: Identify the hormones involved in spermatogenesis and their action. Describe the hormonal control of male reproductive system. Understand the functions of testosterone. Describe the physiological mechanisms of erection and ejaculation. Identify various causes of male and female infertility Understand infertility treatment options and Assisted Reproductive Technologies (ARTs) Hormones involved in spermatogenesis Gonadotrophin-Releasing Hormone (GnRH) released from the hypothalamus stimulates Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) release from the anterior pituitary gland. LH stimulates the Leydig cells in the testis to secrete testosterone. In addition to testosterone, Leydig cells produce other sex hormones that are essential for male development, including dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and estradiol. Testosterone can be converted by aromatase into estrogen and by 5α- reductase into dihydrotestosterone. FSH stimulates the Sertoli cells in the testis and these cells regulate and support spermatogenesis. Sertoli cells also produce inhibin, androgen- binding protein (ABP), and anti-Müllerian hormone (AMH). Growth hormone, prolactin, thyroid hormones, and glucocorticoids could also have an impact on spermatogenesis and male reproductive hormones. 1 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Testosterone Testosterone is a steroid hormone produced by Leydig cells and it is the major androgen in males. Testicular steroidogenesis results in testosterone concentrations that are 100 times higher in the testes than in the circulation. A small amount of testosterone is also secreted by the adrenal glands in both sexes. In addition to intratesticular secretion, testosterone is also released into systemic circulation. Ninety-eight percent of testosterone binds to either sex hormone- binding globulin (SHBG) (65%) or albumin (33%). The remaining 2% remains unbound in the plasma and is free to enter cells and produce its metabolic effects. Testosterone exerts several local and systemic functions (Figures 1 and 2): Testosterone secreted by the fetal testes is responsible for the development of the male phenotype, including the formation of a penis and a scrotum and descent of testes It modulates spermatogenesis and sexual desire. It maintains secondary sexual characteristics in male such as distribution of body hair, male pattern baldness, masculine voice, skin thickness, and development of acne. Muscle development and bone density. Anabolic functions, increase protein synthesis, basal metabolic rate, Red Blood Cells (RBCs), hematocrit, water, and electrolytes retention by the kidney. 2 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Figure 1. Functions of testosterone. Hormonal control of spermatogenesis At the time of puberty, the secretion of hypothalamic GnRH breaks through childhood inhibition resulting in pulsatile GnRH release, and puberty begins. Both LH and FSH, are secreted by gonadotropes in the anterior pituitary gland under the influence of GnRH secretion from the hypothalamus (Figure 1). FSH binds predominantly to the Sertoli cells within the seminiferous tubules to promote spermatogenesis. FSH also stimulates the Sertoli cells to produce hormones including inhibin, which function to inhibit FSH release from the pituitary. Inhibin B could be also a marker of spermatogenic activity. LH binds to receptors on Leydig cells in the testes and upregulates the production of testosterone and other androgens. Testosterone secreted by the testes in response to LH has inhibitory effects on the hypothalamus secretion of GnRH and anterior pituitary secretion of 3 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah LH mostly due to the direct effect of testosterone on the hypothalamus to decrease secretion of GnRH causing a reduction in FSH and LH (negative feedback mechanism) When sperm production by the seminiferous tubules is low, secretion of FSH by the anterior pituitary gland increases markedly. Conversely, when spermatogenesis proceeds too rapidly, pituitary secretion of FSH diminishes. The cause of this negative feedback effect on the anterior pituitary is the secretion of inhibin hormone by Sertoli cells. This hormone has a strong direct inhibitory effect on the anterior pituitary gland secretion of FSH 4 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Figure 2. Hormonal control of spermatogenesis. 5 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Physiology of Erection Penile erection or tumescence refers to the physiologic process during which the penis becomes engorged with blood, usually in response to sexual arousal but sometimes spontaneously. Intact anatomical, neurovascular, hormonal, and molecular factors are essential for erection. The penis consists of three cylindrical chambers: the paired corpora cavernosa and the corpus spongiosum (the erectile tissue of the penis) (Figure 3). Erectile tissue contains a specialized arrangement of arteries, shunts, and venous sinusoids within a matrix of connective tissue and smooth muscle Figure 3. Cross-section in penile tissue. Erection is initiated by dilation of the arterioles and relaxation of sinusoids of the penis. As the erectile tissue of the penis fills with blood, the veins are compressed, blocking outflow and adding to the turgor of the organ. The integrating centers in the lumbar segments of the spinal cord are activated by impulses in afferents from the genitalia and descending tracts 6 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah that mediate erection in response to erotic psychological stimuli. The efferent parasympathetic fibers are in the pelvic splanchnic nerves. Mediators of this response include acetylcholine and the vasodilator vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) Normally, erection is terminated (detumescence) by sympathetic vasoconstrictor impulses to the penile arterioles, smooth muscle contraction and venous expansion. Physiology of Ejaculation Ejaculation is a two-part spinal reflex that involves emission, the movement of the semen into the urethra; and ejaculation proper, the propulsion of the semen out of the urethra at the time of orgasm. The afferent pathways are mostly fibers from receptors in the glans penis that reach the spinal cord through the internal pudendal nerves. Emission is integrated in the lumbar segments of the spinal cord and mediated by contraction of the smooth muscle of the vasa deferens and seminal vesicles in response to stimuli in the hypogastric nerves. The semen is propelled out of the urethra by contraction of the bulbocavernosus muscle. 7 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Abnormalities of the male reproductive system Examples of abnormalities of the male reproductive system include infertility, erectile dysfunction, delayed puberty, hypogonadism and cryptorchidism. Infertility is defined as the inability to achieve pregnancy after 12 months of regular unprotected intercourse. The prevalence is approximately 10-15% and the etiology could be due to male factor, female factor, combined factors while in approximately 20-25% the underlying cause for infertility is unknown and referred to as unexplained infertility. Male infertility could be caused by varicocele, cryptorchidism, genetic, infection, testicular tumors, endocrine disease, systemic disease, anti-sperm antibodies, obstruction of the ejaculatory duct, ejaculatory dysfunction, drugs as well as lifestyle and environmental factors (Figure 4). Female infertility could be causes by ovulatory disorders, fallopian tubes obstruction, uterine disease, cervical pathology and endometriosis (Figure 4). 8 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Figure 4. Causes of male and female infertility 9 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Hypogonadism is defined as a clinical syndrome caused by decreased testosterone levels and concomitant symptoms suggesting androgen deficiency. It is essential to distinguish between primary hypogonadism (which originates in the testes) and secondary hypogonadism (which originates in the hypothalamus or pituitary). Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection adequate for satisfactory sexual activity. The main contributing factors could be organic factors like diabetes, hypertension, hyperlipidemia, or psychological factors. Treatment of Infertility Treatment of infertility is directed toward the underlying cause if it can be identified. Lines of treatment include medical, surgical and Assisted Reproductive Technologies (ARTs). Assisted Reproductive Techniques (ARTs) Assisted Reproductive Techniques (ARTs) comprise a broad category of treatment technologies that include all fertility treatments in which eggs or embryos are handled in vitro and implanted into the uterus. ARTs include Intrauterine and Intracervical Insemination (IUI/ICI), In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) with embryo transfer (ET) and intrafallopian transfer and surgical sperm retrieval (Figure 5). ARTs are most frequently performed in infertility. In patients with tubal factor infertility, IVF directly bypasses the fallopian tubes. Other infertility etiologies in which IVF is employed include male factor infertility, diminished ovarian reserve, ovulatory dysfunction, and unexplained infertility. 10 Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah IVF is the most commonly utilized ART. It involves controlled ovarian stimulation (COS), the collection of oocytes from the ovary, and followed by fertilization in vitro, and is completed with transferring the resulting embryo into a uterus. It involves various steps, including controlled ovarian stimulation, oocyte retrieval, fertilization, embryo culture, and embryo transfer (ET). Additionally, preimplantation genetic testing (PGT) and ICSI may also be included in the process. Cryopreservation with vitrification is then used to freeze excess embryos or gametes for fertility preservation of eggs or embryos. Figure 5. Types of Assisted Reproductive Techniques (ARTs) 11  Male Reproductive Physiology Assis. Prof. Dr. Ahmed Tawfeeq Neamah Suggested further reading and online activities Watch this video (Human Physiology - Hormonal Regulation of Male Reproduction) on Youtube (https://youtu.be/GC58kOcsx9U) Search for the effects of thyroid hormones and prolactin on male reproductive function. Search for the impact of diabetes on erectile function. Read about Blood-Testis Barrier 12