Mullerian-inhibiting substance deficiency in transgenic mice interferes with postnatal germ cell development: clues for understanding infertility in cryptorchidism.

Aim: Mullerian-inhibiting substance (MIS) may have a role in postnatal germ cell development, although this remains unproven. Elucidating the regulatory factors is crucial in finding new treatments for preventing infertility in cryptorchidism. We studied germ cell development in neonatal mice with MIS gene or receptor mutation to determine if germ cell development was affected.

Methods: Neonatal (5 MIS mutants, x1 MIS receptor mutant and 5 wild-type) and 10-day-old mice (x 7 MIS mutants, x1 MIS receptor mutant, 5 wild-type) were killed and prepared for hematoxylin-eosin and Masson trichrome histology of the testis. Testis diameter and tubule diameter were measured by Image-J, and germ cells were counted in 50 tubules/testis.

Results: Total testis and tubular diameters were greater in wild-type vs MIS mutants at days 0 and 10 (P < .01). Gonocytes were decreased in MIS mutants vs wild-type on day 0 (P = .019), and on day 10, the number of type A spermatogonia was slightly decreased (P = .05) and type B spermatogonia were significantly decreased (P < .01). Similar results were seen in the MIS receptor knockout.

Conclusion: These results suggest that MIS has a previously unrecognized role in perinatal germ cell development that needs further investigation. Mullerian-inhibiting substance may be a possible future treatment for stimulating germ cell development in cryptorchidism.