Hypothalamic-adenohypophyseal origin of reproductive failure in mice following chronic infection with Toxoplasma gondii.

Mice chronically infected with Toxoplasma gondii exhibited reproductive failure characterized by a constant diestrous vaginal cytology and ovarian and uterine atrophy. Chronically infected mice were treated with 20 ng of D-Leu6-des-Gly-NH2-Pro-ethylamide (D-Leu6), a structural analog of luteinizing hormone-releasing hormone (LHRH), every 4 hr over a 12-hr period daily, for 3 days. Infected animals treated with D-Leu6 had greater pituitary weight (P less than 0.01), ovarian weight (P less than 0.01), and uterine weight (P less than 0.025), than did infected control mice treated with saline. In addition, a change in vaginal cytology to estrus, metestrus, and proestrus of the D-Leu6-treated animals was observed, although a contiguity of normal estrous cycles and reproductive function was not determined. Comparable basal levels of serum luteinizing hormone (LH) were seen in infected mice and uninfected normal mice. However, the infected animals demonstrated a decreased pituitary responsiveness to D-Leu6 when monitored at 60 (P less than 0.025) and 120 min (P less than 0.010) following intraperitoneal administration of a bolus of 200 ng of the analog. Thus, the observed reproductive failure involves the readily releasable pool of pituitary LH, since basal LH is similar in both groups, and appears to be due to a dysfunction of the hypothalamic-adenohypophyseal axis.