PT  - JOURNAL ARTICLE
AU  - David Fleck
AU  - Lina Kenzler
AU  - Nadine Mundt
AU  - Martin Strauch
AU  - Naofumi Uesaka
AU  - Robert Moosmann
AU  - Felicitas Bruentgens
AU  - Annika Missel
AU  - Artur Mayerhofer
AU  - Dorit Merhof
AU  - Jennifer Spehr
AU  - Marc Spehr
TI  - ATP activation of peritubular cells drives testicular sperm transport
AID  - 10.1101/2020.09.15.298299
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.15.298299
4099  - http://biorxiv.org/content/early/2020/09/16/2020.09.15.298299.short
4100  - http://biorxiv.org/content/early/2020/09/16/2020.09.15.298299.full
AB  - Spermatogenesis, the complex developmental process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility and reproductive fitness. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined. Here, we show that coordinated contractions of smooth muscle-like testicular peritubular cells provide the propulsive force for luminal sperm transport towards the rete testis and epididymis. Using a mouse model for in vivo imaging, we describe and quantify spontaneous tubular contractions and show a causal relationship between peritubular Ca2+ waves and peristaltic transport. Moreover, we identify P2 receptor-dependent purinergic signaling pathways as physiological triggers of tubular contractions both in vitro and in vivo. When challenged with extracellular ATP, transport of luminal content inside the seminiferous tubules displays stage-dependent directionality. We thus suggest that paracrine purinergic signaling coordinates peristaltic recurrent contractions of the mouse seminiferous tubules to propel immotile spermatozoa to the rete testis. Consequently, our findings could have substantial pharmaceutical implications for both infertility treatment and / or male contraception.