Angiotensin-converting enzymes play a dominant role in fertility

Pei-Pei Pan, Qi-Tao Zhan, Fang Le, Ying-Ming Zheng, Fan Jin, Pei-Pei Pan, Qi-Tao Zhan, Fang Le, Ying-Ming Zheng, Fan Jin

Abstract

According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%-20% incidence worldwide. An accumulating body of evidence has shown that the renin-angiotensin system is involved in the fertility problems observed in some populations. Moreover, alterations in the expression of angiotensin-converting enzyme-1, angiotensin-converting enzyme-2, and angiotensin-converting enzyme-3 might be one of the most important mechanisms underlying both female and male infertility. However, as a pseudogene in humans, further studies are needed to explore whether the abnormal angiotensin-converting enzyme-3 gene could result in the problems of human reproduction. In this review, the relationship between angiotensin-converting enzymes and fertile ability is summarized, and a new procedure for the treatment of infertility is discussed.

Figures

Figure 1
Figure 1
Schematic of the local renin–angiotensin system (RAS). AGT and REN are expressed in the liver and kidneys, respectively. Angiotensin peptides are produced through the action of REN, ACE1 and ACE2, all of which are peptidases. Digitals 1–3 refers to ACE1/AngII/AT1R, ACE1/AngII/AT2R and ACE2/Ang-(1–7)/MasR pathways, respectively. There are three main pathways in the ovarian RAS and two main pathways in the testis RAS. AngI (1–10), AngII (1–8), Ang-(1–9) and Ang-(1–7) are decapeptide, octapeptide, nonapeptide and heptapeptide, respectively. The peptide sequence of the AngI (1–10) is Arp-Arg-Val-Tyr-He-His-Pro-Phe-His-Leu. RAS: renin–angiotensin system; AGT: angiotensinogen; REN: renin; AngI: angiotensin I; AngII: angiotensin II; Ang-(1–9): angiotensin-(1–9); Ang-(1–7): angiotensin-(1–7); AT1R: angiotensin II type 1 receptor; AT2R: angiotensin II type 2 receptor; MasR: Mas receptor; ACE1: angiotensin-converting enzyme 1; ACE2: angiotensin-converting enzyme 2.
Figure 2
Figure 2
Mechanisms of sperm–egg interaction. tACE1 and ADAM3 are dispensable factors for the binding of sperm to the zona pellucida, whereas tACE3 and IZUMO1 play important roles in the fusion of gametes to sperm. ADAM: a disintegrin and metalloprotease; ZP: zona pellucida; tACE1: testis angiotensin-converting enzyme 1; tACE3: testis angiotensin-converting enzyme 3.

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