Male Reproductive System - hesiglobal.orghesiglobal.org/.../sites/11/2015/12/...Physiology.pdf · Human Testis and Epididymis • In the inner surface of the capsule is a series of

Overview of Male Reproductive Physiology

Terry R. Brown, Ph.D. Department of Biochemistry & Molecular Biology Johns Hopkins Bloomberg School of Public Health

Undifferentiated Gonad

XX XY Sry

Ovary Testis

GnRH Hypothalamus

Pituitary

LH/hCG

Sertoli cells Leydig cells

MIS/AMH Testosterone

Mullerian duct regression

Wolffian duct development

Testosterone

DHT Androgen Receptor

Gene Expression

Androgen Sensitive Target Cell

Masculinization of Urogenital Sinus and External Genitalia

Mullerian duct development

Wolffian duct regression

MIS/AMH X Testosterone X

Female External Genitalia

Secondary Sex Characteristics

Spermatogenesis

Regulation of Sex Differentiation

Gonadal Differentiation

Human Testis and Epididymis

• In the inner surface of the capsule is a series of fibrous septa that divide the interior of the organ into lobules.

• Lying within each lobule are 1 to 4 coiled seminiferous tubules.

• The tubules open into a network of channels called the rete testis.

• Small efferent ductules connect the rete testis to the upper end of the epididymis

• The epididymis is a single, long coiled duct that courses along the posterolateral side of the testis

Organization of the Mammalian Testis

• FSH promotes spermatogenesis via FSH receptors on Sertoli cells. • LH stimulates testosterone synthesis via LH receptors on Leydig cells. • Sertoli, Leydig and peritubular myoid, but not germ cells express androgen receptors.

Histologic Cross-Section of Testis

Hypothalamic-Pituitary-Testicular Axis Integrates Testicular Function

Sertoli Cell Number in Control, FSHRKO, FSHβKO, Tfm, and Cryptorchid Mice

Johnston H et al. Endocrinology 2004;145:318-329

Leydig Cell Number during Development in Normal Mice and in AR-null Animals

O'Shaughnessy P J et al. J Cell Sci 2002;115:3491-3496

Sertoli and Germ Cell Numbers in 8-wk-old Testes from Control, FSHRKO, SCARKO, and FSHRKO-SCARKO mice.

Abel M H et al. Endocrinology 2008;149:3279-3285

Timing of Testis Descent in Mammals in Relation to Prenatal and Early Postnatal Chronological Age

Hughes I A , Acerini C L Eur J Endocrinol 2008;159:S75-S82

• Testicular descent is dependent upon androgen and insulin-like 3 (Insl3) activities

Species Differences and Similarities in Timing of Critical Events in Testis Development during Gestation.

O'Shaughnessy P J , Fowler P A Reproduction 2011;141:37-46

Regulation of Testicular Function during Fetal Development

O'Shaughnessy P J , Fowler P A Reproduction 2011;141:37-46

Testosterone Levels Vary over Time

Estradiol

Alternative Pathways for Androgen Action

Endocrine Effects of Androgens

Toxicologic End-Points for Testicular Function

• Fertility – spermatogenesis • Phenotype – testicular descent, ano-genital

distance, male genitalia, nipple regression • Endocrine – LH, FSH and testosterone levels • Reproductive tract – testis size, weight and

histology; timing of preputial separation; prostate, seminal vesicle and epididymal weight and histology

Testicular Dysgenesis Syndrome