Hypothalamic-Adenohypophyseal Origin of Reproductive Failure in Mice following Chronic Infection with Toxoplasma gondii

Abstract

Abstract

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-Leu⁶des-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 < 0.01), ovarian weight (P < 0.01), and uterine weight (P < 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 < 0.025) and 120 min (P < 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.