A Critique on the Relevance of Membrane Potentials to the Mechanism of Nidation

Abstract

It has been proposed that contact between the rat blastocyst and the endometrium is conditioned by like electrical charges on their membranes. Clemetson, Mallikarjuneswara, Moshfeghi, Carr & Wilds (1970) and Clemetson, Kim, Mallikarjuneswara & Wilds (1972) presented data purporting to show that treatment of rats with oestrogen or with progesterone could modify the potential of the endometrium and influence contact. Clemetson et al. (1970) stated that 'the high negative membrane potential under the influence of progesterone may be the cause of delayed implantation by repelling the negatively charged blastocyst. Conversely, the lowering of the negative membrane potential under oestrogen treatment could remove or reduce this repelling action and favour contact necessary for attachment and subsequent implantation.' The mechanism by which these changes in potential occurred was attributed to hormonally controlled alterations in the concentrations of sodium and potassium ions in the luminal and intracellular fluids of the endometrial cells. Clemetson et al. (1972) argued that 'the high uterine fluid potassium ion concentration at the time of normal implantation is essential to reduce the membrane potential of the endometrial epithelium in order to allow the negatively charged blastocyst to make contact with it'. Careful scrutiny of the data reveals, however, that their hypotheses are based on one erroneous and one inappropriate assumption. In both papers the potential differences across the luminal membranes of the endometrial cells (transluminal membrane p.d.) were calculated for each hormonal treatment from measured concen¬ trations of sodium and potassium ions in the luminal fluid and from hypothetical values for the intracellular fluid of endometrial cells based on data obtained in the rabbit. The values were inserted into a modified Goldman equation and potential differences (p.d.) of negative polarity were calculated. The polarity of these calculated p.d. revealed that the intracellular bulk phase of the endometrial cells were negative with respect to the luminal fluid bulk phase. Unfortunately, Clemetson et al. confused these negative, transluminal membrane p.d. with a net negative charge on the surface of the luminal membrane of the endometrial cells. The surface charges can be expressed as a 'zeta potential', the value of which decays rapidly within a few Angstroms in a direction normal to the charged surface. The charges that give rise to zeta potential are those that cause electrostatic repulsion or attraction. While such charges may well exist on the surface of the luminal endometrial membranes (as they appear to exist on practically all cell surfaces) they are related only to the charged, dissociated iono-IO END 58

The Implantation Reaction

“…The dose of estrogen used in their experiments was very high, and whatever is meant by "estrogen dominance" it is very unlikely that the very small amounts of estrogen that are secreted during the luteal phase and are necessary for implantation would make estrogen "dominant." Levin (1973) has also criticized their conclusions on the basis that they have confused "the calculated negative transluminal membrane potential difference between two bulk phases with a surface-generated 'zeta potentia!'." However, as stressed by Levin (1973), the fact that these authors' data do not support the concept that the contact between blastocyst and endometrium is governed by hormonally influenced electrostatic surface charges does not invalidate the theory.…”

“…Levin (1973) has also criticized their conclusions on the basis that they have confused "the calculated negative transluminal membrane potential difference between two bulk phases with a surface-generated 'zeta potentia!'." However, as stressed by Levin (1973), the fact that these authors' data do not support the concept that the contact between blastocyst and endometrium is governed by hormonally influenced electrostatic surface charges does not invalidate the theory.…”

The Morphology of Blastocyst Implantation

“…This change is probably a result of intracellular changes in the trophoblast. However, extrinsic factors such as a change in the electrolyte concentration of the uterine secretion (Clemetson, Kim, Mallikarjuneswara & Wilds, 1972;Levin, 1973) or an increase in the neuraminidase activity of the secretion might also be involved. Blastocyst attachment is accompanied by changes in the configuration of the surface of the uterine epithelium.…”

A journey through two lumens!

“…8 It was around this time that I realised that my background and research experience gave me an advantage over nonphysiologists in the sexual/reproductive field who were unaware of, or misinterpreted, basic biological mechanisms. 9 To my surprise even the hallowed Masters and Johnson 5 could go astray: they stated, 'The fact that the vaginal mucosa is a permeable two-way membrane emphasises the difficulty in establishing and maintaining a stable environment' (p 89). My involvement with the ins and outs of ions and fluid across the intestine made it obvious that a 'stable (vaginal) lumenal environment' could actually only be achieved if there was a permeable two-way flux!…”