A new study by Miguel Relloso and colleagues from the Hospital General Universitario Gregorio Marañón in Madrid, Spain, identifies the female sex hormonesas important regulators of the T helper (Th)17 response induced by sperm, and related to dendritic cells (DCs), the key professional antigen-presenting cells.
Sperm is a foreign antigen (material) and its contact with the female reproductive tract elicits an immune/inflammatory response. In many species, sperm is ‘stored’ for days before the arrival of the oocyte, and in humans, fertilization occurs when intercourse takes place up to 6 days before ovulation (A. Wilcox et al., N Engl J Med, 1995; 333:1517). Thus, the passage of sperm through the genital tract and the anti-sperm immunity must be controlled, allowing sperm to survive during ovulation and increasing the chance of fertilization.
Sperm is considered as a weak immunogenic stimulus, and in the female genital tract anti-sperm immunity has been linked almost exclusively to anti-sperm antibodies. The group of Dr. Relloso found, however, that estradiol (E2) inhibited Th17 cell responses, whereas pretreatment with diestrus hormones (progesterone [P] and lower E2) restored the pathogen-host equilibrium.
This study suggests that sperm-pulsed DCs are potent inducers of Th17 responses, and that the survival of the semen – the foreign material in the vagina, may depend mostly from the female hormonal status or environment. Thus, low Th17 response may allow the survival of allogeneic sperm, thus acquiring the ability to fertilize during estrus (with high E2 concentrations). During diestrus (low E2 and high P concentrations), DCs recover their antigen presentation efficiency.
The connection between fungal infections, Th17 immunity and female infertility is well-established. This study is perhaps the first to link the Th17 response to anti-sperm immunity and its regulation by female sex hormones.
The authors propose that a robust and not-controlled Th17 response during estrus may represent an important factor that contributes to infertility. They also suggest that further insights into the hormonal regulation of the reproduction – infection balance and interactions may improve the diagnosis and treatment of fertility and infection problems related to the female genital tract.