Figure 3.
Constitutive activation of FSHR in the absence of LHR partially restores ovarian function and mammary gland development. Key reproductive parameters were assessed via (A) day of vaginal opening and (B) uterine weights in WT, LuRKO /CAM FSHR, CAM FSHR, and LuRKO females. One-way ANOVA conducted using log conversion of uterine weights. a versus b = P < .01. For WT, LuRKO and LuRKO/CAM-FSHR groups, n = 3, for CAM-FSHR group n = 4. (C) Representative images of the mammary gland tissue, internal reproductive tracts and ovaries. Histological characterization of mammary gland wholemounts (upper panel) with a reference point lymph node depicted by yellow arrow toward which ductal elongation occurs demonstrating the rescue of elongation in LuRKO/CAM FSHR female mice, versus rudimentary development in LuRKO females. Macroscopic images (middle panel) showing LuRKO females have thin threadlike uteri, while uteri of LuRKO/CAM FSHR mice resemble that of WT littermates. CAM FSHR expression typically results in hemorrhagic cysts in WT and also in LuRKO background (arrowheads in inserts, the backgrounds has been brightened for clarity). Representative ovarian images (lower panel) from central ovarian cross-sections, with the most advanced follicles in the sample presented. The ovaries of CAM FSHR mice were usually larger than those of WT mice and contain multiple developing follicles and luteinizing follicles (*). The ovaries of LuRKO/CAM FSHR mice have more advanced follicles (an arrow in the inset) than LuRKO mice but lack corpora lutea. A hemorrhagic cyst is marked (arrowhead). Scale bars: the uppermost row 1 mm; middle row 10 mm and inserts 50 mm: lowermost row 500 µm and inserts 250 µm. WT included Lhr+/– females and CAM FSHR in WT and Lhr+/– backgrounds. (D) Representative examples of estrous cycles. Met, metestrous; Di, diestrous; Pro, proestrous; Estr, estrous. Transition stages have been marked between the 2 stages. CAM FSHR females demonstrated variable cycles from seminormal to acyclic, in line with our previous publication (18), of which 1 has been shown here. For smear analyses WT, n = 8; LuRKO, n = 4; CAM-FSHR, n = 13; LuRKO/CAM-FSHR, n = 6.