Infertility Due to Meiotic Disruption in TRIP13-Deficient Meiocytes
Homozygotes of both sexes had small gonads (Figure 2C; see below) and were invariably sterile. Ovaries of adult Trip13Gt/Gt females were severely dysmorphic and had few or no follicles (Figure 3A and 3B). The majority of oocyte loss occurred in late embryogenesis or early in postnatal development, since 2 d postpartum ovaries were markedly smaller than those of control littermates, and were lacking oocytes or newly forming follicles (Figure 3C and 3D). Thus, oocytes failed to progress to the dictyate (resting) phase. Since we observed oocytes with pachytene stage chromosomes in 17.5 d Trip13Gt/Gt embryonic ovaries (unpublished data), this indicates that oocytes were eliminated somewhere between pachynema and dictyate.
Figure 3  Histology of Mutant Gonads
All are hematoxylin/eosin-stained paraffin sections. Testes are from 6-wk-old males, except as indicated below.
(A) Wild-type 25-d-old ovary.
(B) Trip13Gt /Gt 25-d-old ovary, showing dysgenesis from an absence of oocytes.
(C) Trip13Gt/+ 2-d-old control ovary. Arrows point to oocytes in newly forming follicles.
(D) Trip13Gt/Gt 2-d-old ovary, dysgenic due to lack of oocytes. Magnification is the same as its littermate in “C.”
(E) Wild-type testis.
(F) Trip13Gt/Gt testis with uniform pachytene arrest.
(G) Trip13Gt/Gt 3-mo-old testis with some postmeiotic spermatids (arrows).
(H) Spo11−/- testis. A tubule with spermatocytes at leptotene/zygotene transition is labeled ZP, and tubules with apoptotic spermatocytes are marked with an asterisk. The specimen was taken from a littermate of that in (I).
(I) Spo11 −/− Trip13Gt/Gt testis. Labeling is the same as in (H). The inset contains a tubule with leptotene-zygotene spermatocytes.
(J) Mei1 −/− Trip13Gt/+ testis. The specimen was taken from a littermate of that in (K).
(K) Mei1 −/− Trip13Gt/Gt testis.
(L) Rec8Mei8/Rec8Mei8 Trip13Gt/+ testis. The Rec8Mei8 allele was described [39]. The specimen was taken from a littermate of that in (M).
(M) Rec8Mei8/Rec8Mei8 Trip13Gt/Gt testis.
(N) Dmc1 −/− Trip13Gt/Gt testis.
(O) Spo11 −/− Trip13Gt/+ 25-d-old ovary. The specimen was taken from a littermate of that in (P).
(P) Spo11 −/− Trip13Gt/Gt 25-d-old ovary.
(Q) Mei1 −/− Trip13Gt/+ 25-d-old ovary. The specimen was taken from a littermate of that in (R).
(R) Mei1 −/− Trip13Gt/Gt 25-d-old ovary.
(S) Rec8Mei8/Rec8Mei8 Trip13Gt/+ 25-d-old ovary. The specimen was taken from a littermate of that in (T).
(T) Rec8Mei8/Rec8Mei8 Trip13Gt/Gt 25-d-old ovary. Histological sections of mutant testes revealed a lack of postmeiotic cell types that are characteristic of wild-type seminiferous tubules (Figure 3E). The most developmentally advanced seminiferous tubules contained adluminal spermatocytes with condensed chromatin characteristic of pachynema (Figure 3F). The absence of coordinated spermatogenic progression beyond this stage is indicative of a pachytene arrest. This was revealed more clearly by chromosome analysis (see below). Some sections of adult seminiferous tubules contained postmeiotic spermatids (Figure 3G), although we saw no motile epididymal sperm. These drastic meiotic defects stand in contrast to yeast and C. elegans, in which deletion of Pch2 alone has minor effects on spore/gamete development [2,8].