Reproduction Abstracts

Introduction: CSF1 is the primary growth factor required for macrophage proliferation and differentiation. In adults, the receptor is expressed only in macrophages and their precursors. In mice, mutation of the CSF1 gene produces both male and female infertility due to diminished gonadal steroid production. We tested the effect of increased availability of CSF1 on gonadal development in pigs using CSF1-Fc, a CSF1 fusion protein with increased circulating half-life.

Methods: Testicular and ovarian tissue was obtained from 11 9-week old male and female Large White piglets: (CSF1-Fc (0.75 mg/kg) n=6, PBS n=5) for haematoxylin and eosin staining and immunohistochemistry (IHC) using Ki67 as a proliferation marker. Testicular macrophages were detected by IHC using CD163.

Total cell count (TCC), Seminiferous tubules, Seminiferous tubule diameter, Leydig cells (LC), Sertoli cells, Germ cells, proliferating cells (PC) and macrophages were quantified in testis samples (n=5). The number of ovarian follicle types (FT) and PCs were quantified in ovarian samples (n=6).

Results and discussion: The number LCs as a proportion of TCC increased in CSF1-Fc treated animals (meanS.E.M. 0.170.002) compared to PBS controls (0.110.016 P=0.026). Proportion of PCs and LCs compared to TCC also increased in CSF1-Fc treated animals (0.040.0025) compared to PBS controls (0.020.0007 P=0.021). Proportion of proliferating LCs increased in CSF1-Fc treated animals (0.0250.0021) compared to PBS controls (0.0120.0004 P=0.025). No differences were detected in other testis parameters.

In ovarian samples, proportion of multi-oocyte follicles compared to total follicle count significantly increased in CSF1-Fc treated animals (0.090.022) compared to PBS controls (0.020.0017 P=0.042). No differences in number of PCs or other FTs were detected.

These findings suggest that the availability of CSF1 contributes to gonadal cell proliferation in both sexes. The most striking differences occur in males consistent with previous evidence of the role of macrophages in control of LC function.