For Males, an Engineering Marvel that Originates in the Brain

In a previous article, I discussed the irreducible complexity of sperm cells and the seminal fluid for successful fertilization. But the design of sperm cells for successful reproduction is only a part of the story. Also essential is the capability of the male penis to achieve a stable erection and ejaculate the seminal fluid containing the sperm cells into the female vagina. The physiology of this ability is explained in an animation.

The male erection and ejaculatory reflex require multiple physiological processes to work together in an incredible coordinated manner. If any one piece is missing, the objective of ejaculating the seminal fluid into the female vaginal cavity (required for reproduction in humans) will fail. How does this work at the biochemical and physiological level? In what follows, I shall provide a brief overview of this fascinating marvel of human physiology.

Achieving and Sustaining an Erection

Sexual arousal originates in the brain as a result of sensory stimuli, and leads to the activation of the parasympathetic nervous system. A neurotransmitter called acetylcholine is released in response to nerve signals, and in turn stimulates the release of nitric oxide from nerve endings and the endothelium (inner lining) of the penile arteries, which diffuses into smooth muscle cells of the penile arteries and the spongy erectile tissue known as the corpus cavernosum, where it binds to an enzyme called guanylate cyclase. [1] Impairment of the bioactivity of the nitric oxide signaling pathway has in fact been shown to be a contributor to erectile dysfunction. [2] The binding of nitric oxide to guanylate cyclase facilitates the conversion of guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP), which then binds to and activates an enzyme called protein kinase G (also known as cGMP-dependent protein kinase). [3] This is a kinase, a class of enzymes that phosphorylate substrates to result in a conformational change. In the case of protein kinase G, it phosphorylates the myosin light chain in smooth muscle cells (a component of the contractile machinery in these cells), which results in a decrease in myosin’s sensitivity to calcium ions (Ca2+), which are essential for muscle contraction. [4,5] Experiments with mice have revealed that “mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade.” [6]

In smooth muscle cells, calcium ions bind to a protein called calmodulin, forming a complex that activates myosin light chain kinase. When activated, this kinase phosphorylates the myosin light chain, promoting muscle contraction. [7] But elevated levels of cGMP and subsequent activation of protein kinase G leads to the inhibition of myosin light chain kinase, rendering it less effective at phosphorylating the myosin light chain.

In consequence of the decreased levels of phosphorylated myosin light chain, the contractile interactions between myosin and actin are impaired. [8] This leads to relaxation of the smooth muscle cells, as they are unable to contract effectively (in the flaccid state, the penis exists in a constant moderate state of contraction). As a result, the muscle cells do not exert force, allowing blood vessels to dilate (widen), and the smooth muscles within the erectile tissue to relax and become engorged with blood. The increased blood flow fills the erectile tissue, causing the penis to enlarge and become erect. The erectile tissue also exerts pressure on the veins that normally drain blood from the penis. This pressure compresses the veins, reducing the outflow of blood from the penis. This helps to maintain the erection.

To sustain the erection, the balance between the release of nitric oxide and the breakdown of cGMP must be maintained. Phosphodiesterase-5 is an enzyme that breaks down cGMP by cleaving its cyclic phosphate bond, converting it to inactive GMP. [9] This leads to the reversal of smooth muscle relaxation and allows the blood vessels and tissues to return to their normal state. Thus, when sexual arousal subsides or sexual activity is completed, the stimulus for nitric oxide release diminishes, leading to a decrease in cGMP production. The role of phosphodiesterase-5 in breaking down cGMP thus serves as a natural regulatory mechanism to ensure that erections do not persist indefinitely.

For a much more detailed treatment of this subject, I refer interested readers to this review paper on the “Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction.” [10]

The Ejaculation Reflex

Sexual stimuli activate sensory receptors in the genital region, particularly in the head of the penis (called the glans) and surrounding areas, which in turn send nerve signals through sensory nerves to the spinal cord. These nerves are part of the pudendal nerve pathway, which transmits sensory information from the genitalia to the sacral region of the spinal cord, where they are processed by a network of interneurons which relay the signals to motor neurons that control the muscles involved in ejaculation. [11]

Within the sacral spinal cord, there is a specific region known as the spinal ejaculation generator. [12] This center integrates sensory information and coordinates the activation of motor neurons that control the muscles involved in ejaculation, which include smooth muscles of the vas deferens, seminal vesicles, and prostate gland, as well as the skeletal muscles in the pelvic floor region. The initial phase of the ejaculation reflex is called emission. During this phase, the smooth muscles of the vas deferens and associated structures contract rhythmically, propelling sperm and seminal fluid from the testes, epididymis, and accessory glands (seminal vesicles and prostate) into the ejaculatory ducts. The ejaculation reflex also includes the closure of the bladder neck, preventing the backward flow of semen into the bladder. [13]

Rhythmic contractions of the skeletal muscles in the pelvic floor, such as the bulbocavernosus and ischiocavernosus muscles, propel the semen through the urethra and out of the penis. [14] This is accompanied by intense pleasurable sensations (orgasm), which are mediated by the release of neurochemicals such as dopamine and endorphins in the brain. After ejaculation is completed, males typically experience a refractory period during which further sexual arousal and ejaculation are not possible.

Irreducibly Complex

As in the case of so many physiological processes, the male erection and ejaculation reflex requires multiple processes to function in unison to achieve a higher-level objective — in this instance, depositing seminal fluid, containing millions of sperm cells, in the female vaginal cavity. It is implausible that such a complex system arose in a step-wise fashion, as envisioned by neo-Darwinian evolution. Of course, successful ejaculation of the seminal fluid will serve no benefit unless the sperm are able to navigate to, and penetrate, the female egg cells. As I argued in a previous essay, the sperm and seminal fluid are incredibly designed to fulfil this mission — and multiple features of sperm cells and seminal fluid exhibit irreducible complexity, where multiple parts have to work together in unison. This is far better explained by design than by a non-intelligent process involving chance and physical necessity.

Footnotes

1. Alberti C, Frattini A, Ferretti S. Role of nitric oxide in the erectile mechanism. Minerva Urol Nefrol. 1993 Jun;45(2):49-54.

2. Burnett AL. The role of nitric oxide in erectile dysfunction: implications for medical therapy. J Clin Hypertens (Greenwich). 2006 Dec;8(12 Suppl 4):53-62.

3. Francis SH, Busch JL, Corbin JD, Sibley D. cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010 Sep;62(3):525-63.

4. Hathaway DR, Konicki MV, Coolican SA. Phosphorylation of myosin light chain kinase from vascular smooth muscle by cAMP- and cGMP-dependent protein kinases. J Mol Cell Cardiol. 1985 Sep;17(9):841-50.

5. Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, Lincoln TM, Mendelsohn ME. Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. Science. 1999 Nov 19;286(5444):1583-7.

6. Hedlund P, Aszodi A, Pfeifer A, Alm P, Hofmann F, Ahmad M, Fassler R, Andersson KE. Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2349-54.

7. Kamm KE, Stull JT. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol. 1985;25:593-620.

8. DiSanto ME. Corpus cavernosum smooth muscle physiology: a role for sex hormones? J Androl. 2003 Nov-Dec;24(6 Suppl):S6-16.

9. Huang SA, Lie JD. Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P & T. 2013 Jul;38(7):407-19.

10. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005 Nov;32(4):379-95, v.

11. Coolen LM, Allard J, Truitt WA, McKenna KE. Central regulation of ejaculation. Physiol Behav. 2004 Nov 15;83(2):203-15.

12. Allard J, Truitt WA, McKenna KE, Coolen LM. Spinal cord control of ejaculation. World J Urol. 2005 Jun;23(2):119-26.

13. Böhlen D, Hugonnet CL, Mills RD, Weise ES, Schmid HP. Five meters of H(2)O: the pressure at the urinary bladder neck during human ejaculation. Prostate. 2000 Sep 1;44(4):339-41.

14. Gerstenberg TC, Levin RJ, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles. Br J Urol. 1990 Apr;65(4):395-402.

Note: This article was originally published, on September 26 2023, at Evolution News & Science Today.