Testosterone induces activation of porcine primordial follicles in vitro

Abstract

Purpose The mechanism underlying primordial follicle activation is poorly understood. In this study, in-vitro culture and subsequent xenotransplantation were conducted to determine whether testosterone promotes the activation of porcine primordial follicles. Methods Prepubertal porcine ovarian cortical strips containing primordial follicles were cultured in the presence of testosterone for 7 days, and subsequently transplanted to immunodeficient mice for 2 months. After culture and transplantation, development of follicles was examined histologically. The presence of androgen receptors in oocytes was assessed by use of western blot and immunohistochemical analyses. Results Testosterone at 10 -6 M induced the primordial follicle transition to the intermediate (19 ± 4%) and primary (3 ± 1%) stages after 7-day culture, while 56 ± 5% of primordial follicles remained in the initial pool. Higher concentrations, above 10 -5 M, or lower concentrations, below 10 -6 M, did not induce follicle transition to the primary stage. After 7-day culture with 10 -6 M testosterone, ovarian cortical strips were transplanted to immunodeficient mice. Some of the follicles developed to the secondary (15 ± 3%) and antral (10 ± 3%) stages, whereas 44 ± 7% of primordial follicles remained in the initial pool. In the culture experiment, estradiol-17b (10 -7 -10 -5 M) had no significant effect on follicle activation. The androgen receptor antagonist, cyproterone acetate, inhibited the stimulatory effect of testosterone on primordial follicle activation, suggesting an androgen receptormediated action of testosterone. Western blot and immunohistochemical analyses revealed that androgen receptors were present in the oocytes of primordial follicles. Conclusions These results suggest that testosterone at 10 -6 M promotes the activation of porcine primordial follicles in vitro through the androgen receptors in the oocytes.

Androgen actions in the ovary: balance is key

“…1). However, only few studies have so far suggested this concept (Abbott et al 2005, Smith et al 2009, Magamage et al 2011, and in global and GC-specific ARKO mouse models, the number of primordial follicles was normal. Therefore, it is possible that androgens may not be essential for primordial…”

Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: a retrospective cohort study

“…GC-specific ARs seemed to be pivotal regulators of follicular development and fertility. Indeed, androgen has been reported to play roles in recruitment and initiation of primordial follicles [ 35 , 36 ], promotion of follicular growth by increasing FSH receptor expression [ 37 , 38 ], and prevention of follicular atresia by reducing apoptosis [ 37 ]. Moreover, DHEA administration increases serum concentration of insulin-like growth factor-1 (IGF-1) [ 39 ], which has been reported to be correlated with oocyte quality and embryo development [ 40 , 41 ].…”

Transcripts Encoding the Androgen Receptor and IGF-Related Molecules Are Differently Expressed in Human Granulosa Cells From Primordial and Primary Follicles

“…However, the stage of preantral follicle development could not be specified due to the inherent insensitivity of these techniques. Interestingly in this regard, a study cultured porcine primordial follicles in the absence or presence of testosterone, and found that testosterone increased the activation of primordial follicles (Magamage et al, 2011 ). The study further utilized cyproterone acetate, an AR antagonist, which inhibited the stimulatory effect of testosterone on primordial follicle activation.…”