A role for oestrogens in the male reproductive system

Abstract

Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However, both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, oestrogen is present in low concentrations in blood, but can be extraordinarily high in semen, and as high as 250 pg ml(-1) in rete testis fluids, which is higher than serum oestradiol in the female. It is well known that male reproductive tissues express oestrogen receptors, but the role of oestrogen in male reproduction has remained unclear. Here we provide evidence of a physiological role for oestrogen in male reproductive organs. We show that oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. This finding raises further concern over the potential direct effects of environmental oestrogens on male reproduction and reported declines in human sperm counts.

Figure 1

Seminiferous tubules, rete testis and efferent ductules in ERKO and wild-type mice. a, Wild-type seminiferous tubules exhibit normal spermatogenesis and a small rete testis (RT). b, ERKO rete testis and seminiferous tubules (ST) are dilated. Spermatogenesis appears abnormal in several tubules. c, Wild-type efferent ductules (DE) have narrow lumen. d, ERKO efferent ductules have dilated lumen. e, Wild-type efferent-ductule epithelium contains endocytotic vesicles (EV) and numerous PAS+ lysosomes (L). f, ERKO efferent-ductule epithelium is reduced in height and non-ciliated cells (N) contain fewer lysosomes and endocytotic vesicles; C, cilia. Scale bars: a, b, 100 μm; c, d, 50μm; e, f, 10μm.

Figure 2

Testicular mass between 32 and 185 days of age (mean ± s.e.m.). ERKO mass increases at 32-45 and 70-80 days. By 185 days, the ERKO testes are atrophic. Differences were determined by the unpaired Student's t-test (P < 0.05); N = 5-8 for wild-type mice (WT) and N = 7-10 for ERKO.

Figure 3

Change in testis mass 48 h after occlusion of the initial-segment epididymis. Values shown are mean (± s.e.m.) percentage difference between the occluded and sham-operated side. Differences between wild-type (WT) and ERKO means were determined by the unpaired Student's t-test (P < 0.05).

Figure 4

Ligated efferent ductules in vitro. a, Wild-type ductule lumen (between arrows) collapse by 3 h. b, ERKO ductule lumen (between arrows) is wider than wild type and appears to increase in diameter after incubation. c, Wild-type ductule treated with an anti-oestrogen (ICI 182,780) initially has a normal lumen but has a slight reduction in diameter after incubation. Scale bars, 100μm.

Figure 5

The effects of in vitro ligation on changes in luminal area of efferent ductule segments 24 h after ligation. Mean (± s.e.m.) percentage difference between 0 h and 24 h in luminal areas for isolated ductules from wild-type controls, ERKO and ICI-treated mice.