CORRELATION BETWEEN ACE2 AND SARS-CoV-2; THEIR EFFECTS ON HUMAN REPRODUCTIVE SYSTEM:-

HEREDITY HEALTHCARE AND LIFE SCIENCES

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written by : Saptarshi Bhattacharyya.

SARS-CoV-2, characterized by its high rates of mutation is a potential threat to humanity. Many investigations have been conducted on the virus’ mutational profiles, but its effects on the human reproductive system is yet to be adequately elucidated. In this paper, a detailed explanation has been made on how ACE2 is related to the human reproductive system (both male and female) and COVID-19 infection.

SARS-CoV-2 invades the host cell by binding to the ACE2 (Angiotensin converting enzyme) receptor. ACE2 is a key component of Renin-angiotensin system (RAS), which modulates the cleavage of angiotensin II (AngII) and angiotensin(1-7) to exert its physiological mechanisms and functions.

Upon cell invasion, COVID-19 disrupts the RAS system and downregulates ACE2 expression. Thus, concentration of AngII increases, resulting in increased pro-inflammatory response.

ACE2, AngII, Ang(1-7) regulates the basic processes of the human reproductive system like folliculogenesis, steroidogenesis, oocyte maturation, endometrial regeneration, ovulation etc. In females; whereas in males, it regulates testicular functions, sperm functions, sperm’s contribution to embryo quality etc.

Since SARS-CoV-2 enters the cell by binding to the ACE2 receptor, reproductive cells/tissues expressing it are potentially vulnerable to the virus and normal functions can get disrupted.

ACE2 is widely expressed in -

Ovaries, vagina and uterus (thus, the virus impacts the oocyte quality and ovarian functionality);

Placenta (thus, there is a possibility of vertical transmission, leading to complicated pregnancy. Vertical transmission happens if an infected pregnant woman transmits the infection to her fetus/infant during the fetal, intra/postpartum stage. The route of the transmission ranges from placenta, maternal-neonatal contact during parturition or duing breastfeeding. It is found that ACE2 and TMPRSS2 positive cells are present in the human trophoectoderm and placenta throughout the pregnancy period. This suggests that SARS-CoV-2 is susceptible to these tissues and that intra-uterine fetal infection is a potential possibility);

Peri-implantational embryo (it suggests risk during embryo transfer, peri-implantational embryo development and gestation);

Testes and prostate gland (thus, spermiogenesis is negatively affected with reduced motile spermatozoa);

Thus, it is clear that COVID-19 and ACE2 mediated effects befall both male and female reproductive systems in humans. But it is to be noted that ACE2 receptors are more abundant in male human reproductive system than female. Decreased expression of ACE2 is found in the cells of the fallopian tube, ovaries, vagina, cervix and endometrium. Whereas increased expression of ACE2 is found in testes (highest in Leydig and Sertoli cells). Thus, testes are more vulnerable to SARS-CoV-2 than ovaries. Thus, complexities like orchitis and scrotal discomfort, reduction in Leydig cells, and interstitial inflammation are found in male reproductive system.

The above results are collected from observations from COVID-19 infected patients. Detailed molecular level understanding is yet to be explored by the global scientific communities.

In conclusion, ACE2 is specifically important because SARS-CoV-2 spike glycoprotein binds to ACE2. Thus, ACE2 is a potential target for developing specific drugs, antibodies and vaccines. Balancing the RAS mecmechanism may help attenuate the organ complexities in the human reproductive system.

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