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Updated: Jul 8, 2026
Mouse Round Spermatid Injection
Published on: January 26, 2024
Gonadotrophins regulate germ cell survival, not proliferation, in normal adult men
Saleela M Ruwanpura1, Robert I McLachlan, Kati L Matthiesson
1Prince Henry's Institute, Clayton, Level 4, 43-51 Kanooka Grove, Victoria 3168, Australia.
Background:
Gonadotrophins support spermatogenesis via poorly understood mechanisms. We aimed to determine the effect of FSH/LH suppression in regulating germ cell apoptosis and proliferation in normal fertile men.
Methods:
Testicular tissues were obtained after gonadotrophin suppression induced by testosterone alone or combined with depot medroxyprogesterone acetate for 2 or 6 weeks and an untreated group of men (referred to as 'normal men') served as controls (n = 5 or 10 men per group). Apoptosis and proliferation were identified by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) labelling methods, respectively. Intrinsic and extrinsic apoptotic pathways were identified by immunohistochemistry using the pathway-specific proteins: activated caspase (aCaspase) 9 and 8 and quantified using stereological techniques.
Results:
By 2 and 6 weeks, the proportion of TUNEL-labelled spermatogonia increased to 354% and 268% respectively, compared with normal men (P < 0.001), with increased caspase 9 [223 and 166% compared with normal men (P < 0.001)], but no increase in caspase 8, immunoreactivity. At 6 weeks, the proportions of TUNEL-labelled spermatocytes and round spermatids tended to increase (303 and 180% compared with normal men, NS), as did caspase 9 (199 and 147% compared with normal men, NS) and caspase 8 immunoreactivities (286 and 243% compared with normal men, NS and P = 0.06), respectively. The proportion of TUNEL-labelled elongating/elongated spermatids tended to increase (144 and 138% compared with normal men, NS) at 2 and 6 weeks, respectively, with no change in either caspase immunoreactivities. Even though the number of PCNA-labelled cells did not change with gonadotrophin suppression, the balance between proliferation and apoptosis was lower in spermatogonia (P = 0.01) and spermatocytes (P = 0.3) between treated and untreated normal men.
Conclusions:
We demonstrated that gonadotrophins act as spermatogonial survival factors via the regulation of intrinsic apoptotic pathway, whereas having no effect of cellular proliferation in normal men.
Insights
Gonadotrophins are crucial for sperm production, acting as survival factors for spermatogonia by regulating the intrinsic apoptotic pathway. This study found they do not affect germ cell proliferation in fertile men.
Area of Science:
- Reproductive Biology
- Endocrinology
- Spermatogenesis
Background:
- Gonadotrophins (FSH/LH) play a vital role in spermatogenesis, but the precise mechanisms remain unclear.
- Understanding these mechanisms is crucial for reproductive health and potential therapeutic interventions.
Purpose of the Study:
- To investigate the impact of gonadotrophin suppression on germ cell apoptosis and proliferation in normal fertile men.
- To elucidate the role of FSH and LH in regulating the intrinsic and extrinsic apoptotic pathways during spermatogenesis.
Main Methods:
- Gonadotrophin suppression was induced using testosterone alone or combined with depot medroxyprogesterone acetate for 2 or 6 weeks.
- Apoptosis and proliferation were assessed using TUNEL and PCNA staining, respectively.
- Intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic pathways were quantified via immunohistochemistry and stereology.
Main Results:
- Spermatogonia apoptosis significantly increased (354% at 2 weeks, 268% at 6 weeks) with gonadotrophin suppression, linked to elevated caspase 9 activity.
- While apoptosis in spermatocytes and spermatids showed a trend of increase, caspase 8 activity did not significantly rise, suggesting the extrinsic pathway is not involved.
- Germ cell proliferation (PCNA-labelled cells) remained unchanged, indicating gonadotrophins primarily influence survival rather than proliferation.
Conclusions:
- Gonadotrophins function as essential spermatogonial survival factors by modulating the intrinsic apoptotic pathway.
- The study highlights that gonadotrophins do not influence germ cell proliferation in normal fertile men.
- These findings provide critical insights into the hormonal regulation of spermatogenesis and germ cell fate.
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