Revisiting the gonadotropic regulation of mammalian spermatogenesis: evolving lessons during the past decade

Abstract

Spermatogenesis is a multi-step process of male germ cell (Gc) division and differentiation which occurs in the seminiferous tubules of the testes under the regulation of gonadotropins - Follicle Stimulating Hormone (FSH) and Luteinising hormone (LH). It is a highly coordinated event regulated by the surrounding somatic testicular cells such as the Sertoli cells (Sc), Leydig cells (Lc), and Peritubular myoid cells (PTc). FSH targets Sc and supports the expansion and differentiation of pre-meiotic Gc, whereas, LH operates via Lc to produce Testosterone (T), the testicular androgen. T acts on all somatic cells e.g.- Lc, PTc and Sc, and promotes the blood-testis barrier (BTB) formation, completion of Gc meiosis, and spermiation. Studies with hypophysectomised or chemically ablated animal models and hypogonadal (hpg) mice supplemented with gonadotropins to genetically manipulated mouse models have revealed the selective and synergistic role(s) of hormones in regulating male fertility. We here have briefly summarized the present concept of hormonal control of spermatogenesis in rodents and primates. We also have highlighted some of the key critical questions yet to be answered in the field of male reproductive health which might have potential implications for infertility and contraceptive research in the future.

Keywords: blood-testis barrier; gonadotropins; infertility; male fertility; spermatogenesis.

Figure 1

PRISMA flow diagram of selection of articles published in last decade related to gonadotropic regulation of spermatogenesis in mammals.

Figure 2

Hormonal control of spermatogenesis by the hypothalamo-hypophysial-testicular axis through a three-tier neuro-endocrine circuit. Curved blue arrows indicate a renewal of the cells; solid and dotted colored arrows denote the primary action and feedback action of the hormones. A-R, androgen receptor; BTB, blood-testis barrier; FSH, follicle stimulating hormone; FSH-R, FSH receptor; LH, luteinizing hormone; LH-R, LH receptor; T, testosterone. Only one seminiferous tubule has been shown to contain the germ cells; for others, it has been intentionally not shown, only to keep the figure less complicated for viewing of the readers.

Figure 3

Changes in the endocrinal profiles in the course of the development of male gonads from the fetal stages to adulthood. (A, B): Comparison of gonadal cell numbers in rodents and humans. (C, D): Comparison of hormonal levels in rodents and humans. ALc, adult Leydig cell; AMH, anti-Mullerian hormone; FLc, fetal Leydig cell; FSH, follicle stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; NLc, neonatal Leydig cell; Sc, Sertoli cell; T, testosterone.

Figure 4

Comparison of stages of testicular development of the male germ cells among rodents, non-human primates, and humans. Note that the stem cell property differs between rodents and primates; the number of detectable stages of differentiation of the male germ cells varies significantly among all these three groups of animals. Colored curved arrows denote cell renewal; red question marks indicate unknown pathway.