Increase in final stages of follicular atresia and premature decay of corpora lutea in Ins13-deficient mice

Abstract

The insulin-like factor 3 (Ins13), a member of the insulin-like hormone family, is exclusively synthesized in gonads. Our recent analysis of Ins13-deficient mice revealed the regulating role of the Ins13 factor on the gubernaculum development during the transabdominal descent of the testis. Here we define the role of the Ins13 factor by histometric analysis of wild-type and Ins13-/- ovaries. Ovaries from 40-day-old- and 6-month-old Ins13-/- mice as well as from wild-type littermates were serially sectioned. Sections were stained with periodic acid Schiff reaction (PAS) for counting the number of zonae pellucidae which indicated the final stages of follicular atresia. Corpora lutea were also determined. Some sections were processed using either a modified TUNEL method for in situ detection of apoptosis or a lectin labelling technique with Griffonia simplicifolia I agglutinin (GS I) for endothelial cell occurrence. The number of zonae pellucidae was higher in Ins13-deficient ovaries of both ages than in ovaries of wild-type sisters (P<0.05 for 40-day-old ovaries; P < 0.01 for 6-month-old ovaries). Additionally, the wild-type mice of both ages possessed threefold more corpora lutea than their Ins13 littermates (P < 0.01 for 40-day-old; P < 0.001 for 6-month-old). In general, wild-type corpora lutea looked healthy, showed GSI-positive endothelial cells and no apoptotic cells. Corpora lutea from mutants were rich in regressing GS I luteal cells, and apoptotic cells appeared. We conclude: Follicular atresia and luteolysis are accelerated in ovaries of Ins13-deficient mice probably because of increased apoptosis. The Ins13 function thus appears to rescue endocrine cells from the apoptotic pathway. © 2001 Wiley-Liss, Inc.