Impact of Host Reproductive Tract Microbiota on Fertility

Reproductive tract microbiome in a broader sense could be defined as the consortia of microbes that lives internally or externally on reproductive structures, organs or fluid of an organism, and possesses direct link to reproductive structures e.g. gametes via copulation/mating, spawning etc. This term is not just limited to male and female reproductive tracts, gametes and reproductive secretions but it also includes gametes transport structures e.g. spider’s pedipalps as well as genitalia e.g. testis. Substantial research had been done on microbes inhabiting oral, gut and other body regions, especially in pathology perspective but relatively less attention was given on reproductive tract microbiome. With availability of high-throughput technologies especially DNA-sequencing technologies, now researchers are focusing on understanding interaction of male and female reproductive tract microbiota with host and their role in reproductive success, fitness and disorders. Major challenges faced by researchers in study of reproductive tract microbiome includes lack of existing knowledge about microbial inhabitants and in determining whether microbial communities obtained are indigenous to a particular site or are transiently (by chance) transferred to that site due to environmental factor etc. Here is a generalized information about which microbial communities constitute reproductive tract of humans and their beneficial and negative influence on host fertility3.

Influence of Female Reproductive Tract Microbiota:

Female reproductive tract (FRT) could be divided into two parts i.e. upper genital tract (UGT) which includes uterus, fallopian tubes and ovaries and lower genital tract (LGT) which includes vagina and cervix. Vagina contains most of the female reproductive tract bacterial population.Lower FRT is majorly colonized by Lactobacillus species4. There are certain Lactobacillus species that are best adapted to vaginal habitat such that other Lactobacillus species e.g.Lactobacillus acidophilus, could not replace them.There exist a symbiotic relationship between Lactobacillus species and human host where Lactobacillus protects it’s host from invading pathogens e.g. different facultative anaerobes, yeasts etc.5.Different mechanisms that microbes use to provide protection include production of bacteriocins, production of hydrogen peroxide (H2O2), preventing pathogen attachment and inducing epithelial cells, in case of humans, to secrete antimicrobial peptides (AMP) e.g. human beta defensins that would directly influence microbial diversity6. Major contribution of Lactobacillus is the production of lactic acid which turns vaginal environment acidic (pH<4.5). This acidic environment kills wide variety of sexually transmitted pathogens e.g.Neisseria gonorrhoeae, Chlamydia trachomatis5. In return to all these contributions, this bacteria utilizes host glycogen by-products, in order to get energy for it’s activities. Cervix works with vagina to maintain a stable reproductive environment. Rings in cervix region prevents pathogens entry and it’s pre and post ovulation hormonal secretions flushes out microbes out of vagina region7. If there is imbalance in vaginal pH then it could harm sperm, stopping it from fertilizing egg(Why PH Regulation Is So Important For a Healthy Pregnancy, 2019).

In contrast to lower FRT, upper FRT harbors low abundance of microbes. It could be understood from the fact that bacterial load in uterus is ~10,000 times less than that of vagina. Microbial species variety

Reproductive tract microbiome in a broader sense could be defined as the consortia of microbes that lives internally or externally on reproductive structures, organs or fluid of an organism, and possesses direct link to reproductive structures e.g. gametes via copulation/mating, spawning etc. This term is not just limited to male and female reproductive tracts, gametes and reproductive secretions but it also includes gametes transport structures e.g. spider’s pedipalps as well as genitalia e.g. testis. Substantial research had been done on microbes inhabiting oral, gut and other body regions, especially in pathology perspective but relatively less attention was given on reproductive tract microbiome. With availability of high-throughput technologies especially DNA-sequencing technologies, now researchers are focusing on understanding interaction of male and female reproductive tract microbiota with host and their role in reproductive success, fitness and disorders. Major challenges faced by researchers in study of reproductive tract microbiome includes lack of existing knowledge about microbial inhabitants and in determining whether microbial communities obtained are indigenous to a particular site or are transiently (by chance) transferred to that site due to environmental factor etc. Here is a generalized information about which microbial communities constitute reproductive tract of humans and their beneficial and negative influence on host fertility3.

Influence of Female Reproductive Tract Microbiota:

Female reproductive tract (FRT) could be divided into two parts i.e. upper genital tract (UGT) which includes uterus, fallopian tubes and ovaries and lower genital tract (LGT) which includes vagina and cervix. Vagina contains most of the female reproductive tract bacterial population.Lower FRT is majorly colonized by Lactobacillus species4. There are certain Lactobacillus species that are best adapted to vaginal habitat such that other Lactobacillus species e.g.Lactobacillus acidophilus, could not replace them.There exist a symbiotic relationship between Lactobacillus species and human host where Lactobacillus protects it’s host from invading pathogens e.g. different facultative anaerobes, yeasts etc.5.Different mechanisms that microbes use to provide protection include production of bacteriocins, production of hydrogen peroxide (H2O2), preventing pathogen attachment and inducing epithelial cells, in case of humans, to secrete antimicrobial peptides (AMP) e.g. human beta defensins that would directly influence microbial diversity6. Major contribution of Lactobacillus is the production of lactic acid which turns vaginal environment acidic (pH<4.5). This acidic environment kills wide variety of sexually transmitted pathogens e.g.Neisseria gonorrhoeae, Chlamydia trachomatis5. In return to all these contributions, this bacteria utilizes host glycogen by-products, in order to get energy for it’s activities. Cervix works with vagina to maintain a stable reproductive environment. Rings in cervix region prevents pathogens entry and it’s pre and post ovulation hormonal secretions flushes out microbes out of vagina region7. If there is imbalance in vaginal pH then it could harm sperm, stopping it from fertilizing egg(Why PH Regulation Is So Important For a Healthy Pregnancy, 2019).

In contrast to lower FRT, upper FRT harbors low abundance of microbes. It could be understood from the fact that bacterial load in uterus is ~10,000 times less than that of vagina. Microbial species variety and richness in endometrium is higher than that of vagina5. In a study, it was observed that both vagina and gut microbes were found in endometrium samples, as large abundance of microbes inhabiting vagina could cross cervix rings and move to endometrium region. In upper FRT, mostly different species of Lactobacillus colonizes endometrium while follicular fluid is dominated by L. crispatus, L. gasseri, Actinomyces spp. and Propionibacteriummicrobial species8. Figure below shows major bacterial communities that colonizes human female reproductive tract.

and richness in endometrium is higher than that of vagina5. In a study, it was observed that both vagina and gut microbes were found in endometrium samples, as large abundance of microbes inhabiting vagina could cross cervix rings and move to endometrium region. In upper FRT, mostly different species of Lactobacillus colonizes endometrium while follicular fluid is dominated by L. crispatus, L. gasseri, Actinomyces spp. and Propionibacteriummicrobial species8. Figure below shows major bacterial communities that colonizes human female reproductive tract.

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