Reproductive Immunology 101

Reproductive Immunology is a very important yet poorly understood field which affects fertility and pregnancy outcomes. While great progress has been made in applying immunology treatments to fight cancer, improve organ transplant survival, and treat autoimmune disorders, relatively little progress has been made in reproductive medicine. One of the most important recent discoveries in reproductive immune medicine was the identification of HPV virus as the cause of cervical (and other) cancers and subsequent development of HPV vaccines.

Healthy endocrine and immune systems work closely together to enable reproduction while providing immune protection against sexually transmitted infections (STI). Hormonal changes during the menstrual cycle affect the distribution and function of immune cells in the female reproductive tract. For example, estrogen and progesterone hormones affect immune cells in the endometrium to prevent sperm rejection and to prepare the endometrium for implantation of the embryo. In order to create this implantation window for the embryo the immune and endocrine systems inadvertently also create a window of vulnerability during the secretory phase of the menstrual cycle during which the reproductive tract is more susceptible to infections.

Similarly, fluctuation in corticotropin-releasing hormone (CRH) which regulates the stress response predispose women to windows of vulnerability to mood disturbances and autoimmune disorders during key transitions in life including puberty, early menopause, immediately postpartum, and just prior to menstruation (PMS).

Normal ovulation and menstruation trigger cyclic tissue remodeling. The endocrine and immune systems direct activation of blood coagulation and remodeling of local blood vessels. Abnormal inflammation which can be related to infection or an exaggerated immune response contributes to common reproductive disorders including endometriosis, infertility and pregnancy complications.

Anti-inflammatory drugs and drugs that interfere with cyclic tissue remodeling are often used to treat reproductive disorders. Examples include nonsteroidal anti-inflammatory (NSAID) drugs like ibuprofen, steroids like dexamethasone, antibiotics in cases of infection, and hormonal contraceptives which interrupt cyclic tissue remodeling.

ReproductiveImmunology_NewayFertilityZhou JZ, et al. Trends Immunol. 2018 Apr;39(4):302-314.